Jeffrey S Berger, M.D.

RELATIONSHIP BETWEEN BLEEDING AND MORTALITY IN PATIENTS ON DUAL ANTIPLATELET THERAPY VS ASPIRIN ALONE: RESULTS FROM THE CHARISMA TRIAL
Berger, Jeffrey S.; Bhatt, Deepak L.; Steg, Gabriel P.; Steinhubl, Steven R.; Montalescot, Gilles; Shao, Mingyuan; Hacke, Werner; Fox, Keith A.; Berger, Peter B.; Topol, Eric J.; Lincoff, Michael
2011 APR 5 ;57(14):E1237-E1237, Journal of the American College of Cardiology
— id: 134897, year: 2011, vol: 57, page: E1237, stat: Journal Article,

Peripheral artery disease, biomarkers, and darapladib
Berger, Jeffrey S; Ballantyne, Christie M; Davidson, Michael H; Johnson, Joel L; Tarka, Elizabeth A; Lawrence, Denise; Trivedi, Trupti; Zalewski, Andrew; Mohler, Emile R 3rd
2011 May;161(5):972-978, American heart journal
OBJECTIVE: Subjects with peripheral artery disease (PAD) are at increased risk of cardiovascular morbidity and mortality, perhaps in part, related to increased levels of inflammation, platelet activity, and lipids. We therefore sought to investigate the relationship between PAD and levels of inflammatory, platelet, and lipid biomarkers and the treatment effect of darapladib, a novel lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) inhibitor. METHODS: This is a post hoc analysis of the 959 patients with coronary disease or their risk equivalent receiving atorvastatin who were randomized to receive darapladib or placebo to examine the effects of an Lp-PLA(2) inhibitor on the biomarkers of cardiovascular risk. We conducted an exploratory analysis evaluating the levels of biomarkers in subjects with PAD (n = 172) compared with those without PAD (n = 787). RESULTS: After adjustment for age, sex, smoking, body mass index, and diabetes, subjects with PAD had greater levels of matrix metalloproteinase-9 (between group comparisons 22%, 95% confidence interval [10-31], P < .01), myeloperoxidase (12% [2-20], P = .01), interleukin-6 (13% [4-21], P = .01), adiponectin (17% [7-26], P < .01), intercellular adhesion molecule-1 (7% [2-11], P < .01), osteoprotegrin (6% [1-10], P = .02), CD40 ligand (15% [1-28], P = .04), high-sensitivity C-reactive protein (17% [1-31], P = .04), and triglycerides (11% [0.2-21], P = .05). No significant difference was detected for Lp-PLA(2) activity, P-selectin, urinary 11-dehydrothroboxane B2, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol between subjects with and without PAD. Darapladib produced highly significant inhibition of Lp-PLA(2) activity when compared with placebo at weeks 4 and 12 (P < .01) in patients with and without PAD. CONCLUSIONS: Subjects with PAD had elevated levels of matrix metalloproteinase-9, myeloperoxidase, interleukin-6, adiponectin, intercellular adhesion molecule-1, osteoprotegrin, CD40 ligand, high-sensitivity C-reactive protein, and triglycerides compared with those without PAD. Darapladib, a novel Lp-PLA(2) inhibitor, was equally effective in reducing Lp-PLA(2) activity levels in subjects with and without PAD
— id: 132589, year: 2011, vol: 161, page: 972, stat: Journal Article,

Bleeding, mortality, and antiplatelet therapy: Results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial
Berger, Jeffrey S; Bhatt, Deepak L; Steg, P Gabriel; Steinhubl, Steven R; Montalescot, Gilles; Shao, Mingyuan; Hacke, Werner; Fox, Keith A; Berger, Peter B; Topol, Eric J; Lincoff, A Michael
2011 Jul;162(1):98-105.e1, American heart journal
BACKGROUND: The association between bleeding severity and cause of mortality in the non-acute setting is unclear. We sought to investigate the association between bleeding and mortality subtype, and assess whether this association differs in patients on dual antiplatelet therapy (DAPT) versus aspirin alone. METHODS: Using multivariable Cox proportional hazards survival regression, we examined the association between moderate or severe bleeding and all-cause, cardiovascular, and cancer mortality in 15,603 patients with cardiovascular disease or multiple risk factors enrolled in the CHARISMA trial. RESULTS: Patients with moderate or severe bleeding had a higher incidence of all-cause, cardiovascular, and cancer mortality (P < .001 for each). After multivariable adjustment, moderate/severe bleeding remained independently associated with not only all-cause mortality (adjusted hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.24-2.21) and cardiovascular mortality (HR 2.05, 95% CI 1.38-3.04) but also cancer mortality (HR 4.76, 95% CI 2.60-8.69). However, there was a significant interaction between bleeding and potency of antiplatelet therapy for all-cause (P = .002), cardiovascular (P = .02), and cancer mortality (P = .03); in subjects on aspirin alone, moderate/severe bleeding was associated with all-cause (HR 5.27, 95% CI 3.56-7.80), cardiovascular (HR 4.33, 95% CI 2.55-7.37), and cancer mortality (HR 9.01, 95% CI 4.41-18.43), but not in subjects on DAPT (all-cause: HR 1.48, 95% CI 0.93-2.34; cardiovascular: HR 1.04, 95% CI 0.58-1.86; and cancer mortality: HR 1.79, 95% CI 0.56-5.74). CONCLUSIONS: In stable patients, moderate or severe bleeding is associated with a significantly increased risk of all-cause, cardiovascular, and cancer mortality. However, this risk appeared different in subjects on single antiplatelet therapy versus DAPT
— id: 135265, year: 2011, vol: 162, page: 98, stat: Journal Article,

Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: A meta-analysis of randomized trials
Berger, Jeffrey S; Lala, Anuradha; Krantz, Mori J; Baker, Gizelle S; Hiatt, William R
2011 Jul;162(1):115-124.e2, American heart journal
BACKGROUND: The benefit of aspirin to prevent cardiovascular events in subjects without clinical cardiovascular disease relative to the increased risk of bleeding is uncertain. METHODS: A meta-analysis of randomized trials of aspirin versus placebo/control to assess the effect of aspirin on major cardiovascular events (MCEs) (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), individual components of the MCE, stroke subtype, all-cause mortality, and major bleeding. Nine trials involving 102,621 patients were included: 52,145 allocated to aspirin and 50,476 to placebo/control. RESULTS: Over a mean follow-up of 6.9 years, aspirin was associated with a reduction in MCE (risk ratio [RR] 0.90, 95% CI 0.85-0.96, P < .001). There was no significant reduction for myocardial infarction, stroke, ischemic stroke, or all-cause mortality. Aspirin was associated with hemorrhagic stroke (RR 1.35, 95% CI 1.01-1.81, P = .04) and major bleeding (RR 1.62, 95% CI 1.31-2.00, P < .001). In meta-regression, the benefits and bleeding risks of aspirin were independent of baseline cardiovascular risk, background therapy, age, sex, and aspirin dose. The number needed to treat to prevent 1 MCE over a mean follow-up of 6.9 years was 253 (95% CI 163-568), which was offset by the number needed to harm to cause 1 major bleed of 261 (95% CI 182-476). CONCLUSIONS: The current totality of evidence provides only modest support for a benefit of aspirin in patients without clinical cardiovascular disease, which is offset by its risk. For every 1,000 subjects treated with aspirin over a 5-year period, aspirin would prevent 2.9 MCE and cause 2.8 major bleeds
— id: 135266, year: 2011, vol: 162, page: 115, stat: Journal Article,

Percutaneous coronary intervention for acute coronary syndromes: no difference in 30-day efficacy or safety of high- and low-dose aspirin; double-dose clopidogrel reduces 30-day risk of cardiovascular death, myocardial infarction or stroke compared with standard dose but increases risk of major bleeding
Lala, Anuradha; Berger, Jeffrey S
2011 Jun;16(3):80-81, Evidence Based Medicine
— id: 132569, year: 2011, vol: 16, page: 80, stat: Journal Article,

PLATELET SIZE IS AN EXCELLENT SURROGATE FOR INCREASED PLATELET ACTIVITY
Merolla, Michael; Nardi, Michael A.; Hu, Liang; Rockman, Caron B.; Berger, Jeffrey S.
2011 APR 5 ;57(14):E1600-E1600, Journal of the American College of Cardiology
— id: 134898, year: 2011, vol: 57, page: E1600, stat: Journal Article,

Coronary artery disease, aspirin, and perioperative myocardial infarction and bleeding in orthopedic surgery
Oberweis B.; Nukala S.; Rosenberg A.; Stuchin S.; Radford M.J.; Berger J.S.
2011 ;32:172-172, European heart journal
Purpose: Increasing numbers of patients with established coronary artery disease (CAD) are undergoing surgical procedures. Since patients with CAD are at increased risk for both thrombotic and bleeding complications during the perioperative state, the role of antiplatelet therapy in this setting remains elusive. We therefore sought to investigate the incidence of thrombotic and bleeding events, as well as to identify significant risk factors. Methods: For all 3295 knee, hip, and spine surgical procedures performed November 2008 - December 2009 at a tertiary care medical care center we determined the presence or absence of CAD, CAD risk factors, and post-operative myocardial infarction or hemorrhage using ICD-9 diagnosis codes. 3083 patients were found to be eligible for the study after 212 patients less than 21 years were excluded from the study. Transfusion data were ascertained from the blood bank. Perioperative aspirin use and troponin elevation were determined through retrospective medical record review for all 327 CAD cases. Results: Overall, the in-hospital incidence was higher in patients with CAD (n=327) versus without CAD (n=2756) for any troponin elevation (19.3% vs 4.2%, P<0.001), coded MI (2.1% vs 0.5%, P<0.001), >= 2 transfusions of packed red blood cells (33.6% vs 16.6%, P<0.001), and coded post-operative hemorrhage (2.1% vs 0.7%, P=0.01). Among patients with CAD, use of aspirin preoperatively was not associated with any troponin elevation (6.6% vs 13.2%, P=0.23) or >= 2 transfusion units (6.8% vs 9.7%, P=0.29). In fact, the use of aspirin in the preoperative state was associated with fewer coded MI's (7.5% vs 14.3%, P=0.05). Conclusions: Patients with CAD undergoing orthopedic surgery are at a significant risk for both ischemic and bleeding complications. A lower risk of MI was seen in patients with CAD who were on preoperative aspirin, yet, there was no increase in bleeding outcomes. Future prospective studies are needed to address the potential perioperative role of aspirin and the trade-off between ischemic and bleeding complications among surgical patients with CAD
— id: 137913, year: 2011, vol: 32, page: 172, stat: Journal Article,

Outcome of carotid artery interventions among female patients, 2004 to 2005
Rockman, Caron B; Garg, Karan; Jacobowitz, Glenn R; Berger, Jeffrey S; Mussa, Firas F; Cayne, Neal S; Adelman, Mark A; Maldonado, Thomas S
2011 Jun;53(6):1457-1464, Journal of vascular surgery
BACKGROUND: The benefit of carotid endarterectomy (CEA) in female patients has been questioned by various randomized, prospective trials, particularly in asymptomatic cases; several have noted an increase in perioperative stroke among women after CEA. The outcome of carotid angioplasty and stenting (CAS) has not been extensively examined in women. This study examined the outcome of CEA and CAS in women vs men by using a national database. METHODS: Outcomes of CEA and CAS were stratified by sex using discharge data from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. The NIS was used to identify patient discharges that occurred during 2004 and 2005. Appropriate International Classification of Diseases, 9th Revision (ICD-9) procedure and diagnosis codes were used to identify CEA and CAS cases. Outcome measures included in-hospital perioperative stroke and death. Comparisons of demographics, procedures, and outcome were performed between men and women. Additional analysis was performed among women alone to attempt to identify whether improved outcome was noted with either procedure. RESULTS: Of 54,658 procedures, 94.2% were CEA and 5.8% were CAS. Women comprised 42.3% of the analyzed cases. Women and men were equally likely to be symptomatic (5.3% vs 5.3%, P = .8). Women were significantly less likely to undergo CAS than men (5.4% vs 6.1%, P < .001). Women and men had equivalent rates of perioperative stroke when undergoing CEA (1.0% vs 1.0%, P = .9) and CAS (2.7% vs 2.0%, P = .2). Symptomatic women had a significantly higher rate of perioperative stroke overall than did symptomatic men (3.8% vs 2.3%, P = .03). Asymptomatic women had a significantly lower perioperative stroke rate after CEA than after CAS (0.9% vs 2.1%, P < .001). Rates of perioperative showed a trend favoring CEA vs CAS among symptomatic women (3.4% vs 6.2%, P = .1). CONCLUSIONS: The concern regarding an increased perioperative stroke rate after CEA among asymptomatic women appears to be unfounded. The perioperative stroke rate among symptomatic women was higher than that of symptomatic men, but still well within the acceptable range for symptomatic patients undergoing a cerebrovascular intervention. Nationally, women underwent CAS significantly less frequently than did men. Outcome among women for perioperative stroke favored CEA over CAS, particularly in asymptomatic patients. CEA may be the preferred treatment in women seeking intervention for cerebrovascular disease, unless compelling reasons exist to perform CAS
— id: 132879, year: 2011, vol: 53, page: 1457, stat: Journal Article,

Interpreting the EVAR versus OPEN Repair Randomized Trials: A Critical Meta-Analysis
Rockman, Caron; Rubin, Maya; Adelman, Mark A.; Veith, Frank; Berger, Jeffrey S.
2011 FEB ;53(2):554-554, Journal of vascular surgery
— id: 126448, year: 2011, vol: 53, page: 554, stat: Journal Article,

Platelet activity and cardiovascular risk in apparently healthy individuals: a review of the data
Sharma G; Berger JS
2011 Aug;32(2):201-208, Journal of thrombosis & thrombolysis
Cardiovascular disease is a major cause of morbidity and mortality. Numerous risk scores exist to identify healthy individuals at increased risk of developing cardiovascular disease. Although platelets are a key mediator in the pathogenesis of cardiovascular disease, the role of platelet activity measurements and the incidence of cardiovascular disease are uncertain. Platelet aggregometry-the most well studied method of platelet function testing-is associated with risk factors for cardiovascular disease. However, data supporting platelet aggregation and incident cardiovascular disease is conflicting. Plasma markers of platelet activation are promising candidates. Soluble CD40L and P-selectin are easily measured with a standardized ELISA, and there is some data to suggest an association with cardiovascular disease, but further studies are required. While mean platelet volume is a promising candidate, platelet count and bleeding time are not specific for platelet activity nor are they associated with cardiovascular disease in a healthy population. For this field to progress, we recommend large-scale, prospective studies that measure a battery of these platelet function tests in individuals without cardiovascular disease to better understand the associations, if any, between platelet activity and cardiovascular disease
— id: 134431, year: 2011, vol: 32, page: 201, stat: Journal Article,

Reply
Berger J.S.; Jordan C.O.; Lloyd-Jones D.; Blumenthal R.S.
2010 ;56(9):743-744, Journal of the American College of Cardiology
— id: 112210, year: 2010, vol: 56, page: 743, stat: Journal Article,

Aspirin as preventive therapy in patients with asymptomatic vascular disease
Berger, Jeffrey S
2010 Mar 3;303(9):880-882, JAMA
— id: 107731, year: 2010, vol: 303, page: 880, stat: Journal Article,

Mean platelet volume and prevalence of peripheral artery disease, the National Health and Nutrition Examination Survey, 1999-2004
Berger, Jeffrey S; Eraso, Luis H; Xie, Dawei; Sha, Daohang; Mohler, Emile R 3rd
2010 Dec;213(2):586-591, Atherosclerosis
OBJECTIVES: We sought to determine whether mean platelet volume (MPV) is associated with the prevalence of peripheral artery disease (PAD). BACKGROUND: Platelets play a pivotal role in the pathogenesis of atherosclerosis and PAD. MPV, a measure of platelet size available in every blood count, is increasingly recognized as an important marker of platelet activity. METHODS: We analyzed data from 6354 participants aged 40 years and older from the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population. PAD was defined as an ankle brachial index </=0.90 in either leg. Odds ratios and 95% confidence intervals were estimated by logistic regression. RESULTS: The prevalence of PAD in the cohort was 5.7%. MPV was significantly associated with PAD prevalence (tertile 1 - 4.4%, tertile 2 - 6.1%, tertile 3 - 7.0%, P for trend=0.003). After adjustment for age, sex, and race, the odds ratio of PAD comparing the highest tertile to the lowest tertile was 1.57 (95% confidence interval 1.15-2.13). After further adjustment for smoking status, hypertension, hypercholesterolemia, diabetes, glomerular filtration rate, body mass index, and platelet count the corresponding odds ratio was 1.58 (95% confidence interval 1.14-2.19). The addition of triglycerides, hemoglobin A1c, and C-reactive protein did not affect the results. The significant association between MPV and PAD was unchanged when MPV was used as a continuous variable. CONCLUSIONS: Mean platelet volume is independently associated with PAD. These findings support the hypothesis that platelet size is an independent predictor of increased risk for PAD
— id: 115273, year: 2010, vol: 213, page: 586, stat: Journal Article,

Screening for cardiovascular risk in asymptomatic patients
Berger, Jeffrey S; Jordan, Courtney O; Lloyd-Jones, Donald; Blumenthal, Roger S
2010 Mar 23;55(12):1169-1177, Journal of the American College of Cardiology
Cardiovascular disease is the number 1 cause of death in the western world and 1 of the leading causes of death worldwide. The lifetime risk of atherosclerotic cardiovascular disease (CVD) for persons at age 50 years, on average, is estimated to be 52% for men and 39% for women, with a wide variation depending on risk factor burden. Assessing patients' cardiovascular risk may be used for the targeting of preventive treatments of individual patients who are asymptomatic but at sufficiently high risk for the development of CVD. Risk stratifying patients for CVD remains challenging, particularly for those with low or intermediate short-term risk. Several algorithms have been described to facilitate the assessment of risk in individual patients. We describe 6 risk algorithms (Framingham Risk Score for coronary heart disease events and for cardiovascular events, Adult Treatment Panel III, SCORE [Systematic Coronary Risk Evaluation] project, Reynolds Risk Score, ASSIGN [Assessing Cardiovascular Risk to Scottish Intercollegiate Guidelines Network/SIGN to Assign Preventative Treatment], and QRISK [QRESEARCH Cardiovascular Risk Algorithm]) for outcomes, population derived/validated, receiver-operating characteristic, variables included, and limitations. Areas of uncertainty include 10-year versus lifetime risk, prediction of CVD or coronary heart disease end points, nonlaboratory-based risk scores, age at which to start, race and sex differences, and whether a risk score should guide therapy. We believe that the best high-risk approach to CVD evaluation and prevention lies in routine testing for cardiovascular risk factors and risk score assessment. We recommend that health care providers discuss the global cardiovascular risk and lifetime cardiovascular risk score assessment with each patient to better explain each patient's future risk. Appropriate intervention, guided by risk assessment, has the potential to bring about a significant reduction in population levels of risk
— id: 108796, year: 2010, vol: 55, page: 1169, stat: Journal Article,

Response to Letter Regarding Article, "Smoking, Clopidogrel, and Mortality in Patients With Established Cardiovascular Disease"
Berger, JS; Bhatt, DL; Steinhubl, SR; Shao, M; Lincoff, AM; Steg, PG; Montalescot, G; Hacke, W; Fox, KA; Topol, EJ; Berger, PB
2010 JUL 20 ;122(3):E395-E395, Circulation
— id: 111528, year: 2010, vol: 122, page: E395, stat: Journal Article,

Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis
Chu, S G; Becker, R C; Berger, P B; Bhatt, D L; Eikelboom, J W; Konkle, B; Mohler, E R; Reilly, M P; Berger, J S
2010 Jan;8(1):148-156, Journal of thrombosis & haemostasis : JTH
Summary Aim: To determine if an association exists between mean platelet volume (MPV) and acute myocardial infarction (AMI) and other cardiovascular events. Platelet activity is a major culprit in atherothrombotic events. Mean platelet volume, widely available in clinical practice, is a potentially useful biomarker of platelet activity in the setting of cardiovascular disease. Methods and Results: We performed a systematic review and meta-analysis investigating the association between MPV and AMI, all-cause mortality following MI, and restenosis following coronary angioplasty. Results were pooled using random effects modeling. Pooled results from 16 cross-sectional studies involving 2,809 patients investigating the association of MPV and AMI indicated that MPV was significantly higher in those with AMI than those without AMI (mean difference 0.92 fl, 95% confidence interval [CI] 0.67 to 1.16, P < 0.001). In subgroup analyses, significant differences in MPV existed between subjects with AMI versus stable coronary disease (P < 0.001) and versus stable controls (P < 0.001), but not versus unstable angina (P = 0.24). Pooled results from three cohort studies involving 3,184 patients evaluating the risk of death following AMI, demonstrated that an elevated MPV increased the odds of death compared with a normal MPV (11.5% versus 7.1%, odds ratio 1.65, 95% CI 1.12 to 2.52, P = 0.012). Pooled results from five cohort studies involving 430 patients who underwent coronary angioplasty revealed that MPV was significantly higher in patients who developed restenosis compared with those who did not develop restenosis (mean difference 0.98 fl, 95% CI 0.74 to 1.21, P < 0.001). Conclusions: Elevated MPV is associated with AMI, mortality following MI, and restenosis following coronary angioplasty. These data suggest that MPV is a potentially useful prognostic biomarker in patients with cardiovascular disease. Whether the relationship is causal, and whether MPV should influence practice or guide therapy remains unknown
— id: 102617, year: 2010, vol: 8, page: 148, stat: Journal Article,

An aspirin a day: are we barking up the wrong willow tree?
Krantz, Mori J; Berger, Jeffrey S; Hiatt, William R
2010 Feb;30(2):115-118, Pharmacotherapy
— id: 106386, year: 2010, vol: 30, page: 115, stat: Journal Article,

Representation of Women in Randomized Clinical Trials of Cardiovascular Disease Prevention
Melloni, Chiara; Berger, Jeffrey S; Wang, Tracy Y; Gunes, Funda; Stebbins, Amanda; Pieper, Karen S; Dolor, Rowena J; Douglas, Pamela S; Mark, Daniel B; Newby, L Kristin
2010 Mar 1;3(2):135-142, Ciculation : Cardiovascular quality & outcomes
Background The 2007 American Heart Association guidelines for cardiovascular disease prevention in women drew heavily on results from randomized clinical trials; however, representation of women in trials of cardiovascular disease prevention has not been systematically assessed. Methods and Results We abstracted 156 randomized clinical trials cited by the 2007 women's prevention guidelines to determine female representation over time and by clinical indication, prevention type, location of trial conduct, and funding source. Both women and men were represented in 135 of 156 (86.5%) trials; 20 trials enrolled only men; 1 enrolled only women. Among all trials, the proportion of women increased significantly over time, from 9% in 1970 to 41% in 2006. Considering only trials that enrolled both women and men, female enrollment was 18% in 1970 and increased to 34% in 2006. Female representation was higher in international versus United States\Nonly trials (32.7% versus 26.7%) and primary versus secondary prevention trials (42.6% versus 26.6%). Female enrollment was comparable in government/foundation-funded versus industry-funded trials (31.9% versus 31.5%). Representation of women was highest among trials in hypertension (44%), diabetes (40%), and stroke (38%) and lowest for heart failure (29%), coronary artery disease (25%), and hyperlipidemia (28%). By contrast, women accounted for 53% of all individuals with hypertension, 50% with diabetes, 51% with heart failure, 49% with hyperlipidemia, and 46% with coronary artery disease. Sex-specific results were discussed in only 31% of primary trial publications. Conclusions Enrollment of women in randomized clinical trials has increased over time but remains low relative to their overall representation in disease populations. Efforts are needed to reach a level of representation that is adequate to ensure evidence-based sex-specific recommendations
— id: 107732, year: 2010, vol: 3, page: 135, stat: Journal Article,

Aspirin as an antiplatelet agent
Berger JS
2009 ;9:84-89, Heart attack & acute coronary syndrome
— id: 105331, year: 2009, vol: 9, page: 84, stat: Journal Article,

Platelet-directed therapies and coronary artery bypass grafting
Berger, Jeffrey S
2009 Sep 7;104(5 Suppl):44C-48C, American journal of cardiology
Coronary artery bypass grafting (CABG) is effective in reducing cardiovascular morbidity and mortality in certain high-risk groups. Despite improvement in surgical technique, hemorrhagic complications are a major concern and are likely to affect perioperative morbidity and mortality, length of stay, and hospital expenditures. The use of platelet-directed therapies in this setting is effective in decreasing ischemic complications, yet these agents simultaneously increase the risk of bleeding. Concern about potential hemorrhagic risk from antiplatelet agents in proximity to CABG may influence physicians to discontinue these agents. The benefit of low-dose aspirin given preoperatively is likely to outweigh any hemorrhagic risk. Dual antiplatelet therapy with aspirin and clopidogrel (or aspirin and prasugrel) is associated with a significant increased risk of bleeding and its complications. Additional research is needed to properly evaluate the ischemic benefit versus bleeding risk of aspirin and clopidogrel. Whether reversible P2Y(12) receptor antagonists will mitigate the bleeding risk is unclear at the present time and will require large prospective studies
— id: 101895, year: 2009, vol: 104, page: 44C, stat: Journal Article,

A clinician's perspective of emerging P2Y(12)-directed pharmacotherapies, ex vivo measurement tools, and clinical outcomes
Berger, Jeffrey S; Becker, Richard C
2009 Aug;20(5):302-315, Platelets
Platelet-initiated acute thrombosis and coronary embolization are fundamental to the pathophysiology of acute coronary syndromes. Pharmacotherapies aimed at disrupting platelet function via the P2Y(12) receptor have been successful at reducing the incidence of vascular events in randomized clinical trials. However, with the emergence of third and fourth generation drugs, several important considerations remain, including metabolism, timing of onset, variability in platelet response or 'resistance', monitoring ability, and off-target effects. These fundamental properties and distinct profiles may shape the future of cardiovascular therapeutics. Investigation of practical ex vivo platelet performance measurement tools is actively proceeding and may provide important information for patient management
— id: 101293, year: 2009, vol: 20, page: 302, stat: Journal Article,

The relative efficacy and safety of clopidogrel in women and men a sex-specific collaborative meta-analysis
Berger, Jeffrey S; Bhatt, Deepak L; Cannon, Christopher P; Chen, Zhengming; Jiang, Lixin; Jones, James B; Mehta, Shamir R; Sabatine, Marc S; Steinhubl, Steven R; Topol, Eric J; Berger, Peter B
2009 Nov 17;54(21):1935-1945, Journal of the American College of Cardiology
OBJECTIVES: This study sought to investigate the efficacy and safety of clopidogrel in women and men. BACKGROUND: Previous analyses have shown sex-based differences in response to several antiplatelet medications. Little is known about the efficacy and safety of clopidogrel in women and men. METHODS: This study performed a meta-analysis of all blinded randomized clinical trials comparing clopidogrel and placebo (CURE [Clopidogrel in Unstable Angina to Prevent Recurrent Events], CREDO [Clopidogrel for the Reduction of Events During Observation], CLARITY-TIMI 28 [Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28], COMMIT [Clopidogrel and Metoprolol in Myocardial Infarction Trial], and CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance] trials), involving a total of 79,613 patients, of whom 30% were women. The relative efficacy and safety of clopidogrel at reducing cardiovascular events (cardiovascular death, myocardial infarction [MI], or stroke) in women and men was estimated using random-effects modeling. RESULTS: Overall, clopidogrel was associated with a highly significant 14% proportional reduction in the risk of cardiovascular events (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93), with no significant differences in treatment effect between women and men. Among the 23,533 women enrolled, there were fewer cardiovascular events in the clopidogrel group compared with the placebo group (11.0% vs. 11.8%; OR: 0.93; 95% CI: 0.86 to 1.01). In women the risk reduction with clopidogrel seemed to be greatest for MI (OR: 0.81; 95% CI: 0.70 to 0.93), with the effects on stroke (OR: 0.91; 95% CI: 0.69 to 1.21) or total death (OR: 0.99; 95% CI: 0.90 to 1.08) not statistically significant. Among the 56,091 men enrolled, there were fewer cardiovascular events in those receiving clopidogrel compared with placebo (7.8% vs. 9.0%; OR: 0.84; 95% CI: 0.78 to 0.91), and the risk reduction was significant for MI (OR: 0.83; 95% CI: 0.76 to 0.92), stroke (OR: 0.83; 95% CI: 0.71 to 0.96), and total death (OR: 0.91; 95% CI: 0.84 to 0.97). Clopidogrel increased the risk of major bleeding in both women (OR: 1.43; 95% CI: 1.15 to 1.79) and men (OR: 1.22; 95% CI: 1.05 to 1.42). CONCLUSIONS: Clopidogrel reduces the risk of cardiovascular events in both women and men
— id: 105329, year: 2009, vol: 54, page: 1935, stat: Journal Article,

Smoking, clopidogrel, and mortality in patients with established cardiovascular disease
Berger, Jeffrey S; Bhatt, Deepak L; Steinhubl, Steven R; Shao, Mingyuan; Steg, P Gabriel; Montalescot, Gilles; Hacke, Werner; Fox, Keith A; Lincoff, A Michael; Topol, Eric J; Berger, Peter B
2009 Dec 8;120(23):2337-2344, Circulation
BACKGROUND: Smoking increases platelet aggregability and the degree of platelet inhibition by clopidogrel on ex vivo platelet function tests. Whether smoking status affects the relationship between clopidogrel and clinical outcomes is unknown. METHODS AND RESULTS: We evaluated the relationship between smoking status (current smoker, former smoker, or never-smoker) and treatment with clopidogrel on the risk of all-cause, cardiovascular, and cancer mortality among the 12 152 participants from the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial who had established cardiovascular disease. Current smoking was associated with an increase in all-cause (adjusted hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.85 to 3.60), cardiovascular (HR 2.26, 95% CI 1.48 to 3.45), and cancer (HR 3.56, 95% CI 1.96 to 6.46) mortality compared with never smoking. The impact of clopidogrel on mortality differed by smoking status (P for interaction=0.018 for current smokers). Among current smokers, clopidogrel was associated with a reduction in all-cause mortality (HR 0.68, 95% CI 0.49 to 0.94); clopidogrel did not reduce all-cause mortality among former smokers (HR 0.95, 95% CI 0.75 to 1.19) or never-smokers (HR 1.14, 95% CI 0.83 to 1.58). A similar pattern was noted for cardiovascular mortality. As expected, no relationship was observed between clopidogrel and cancer mortality by smoking status. The risk of bleeding appeared to differ according to smoking status; randomized clopidogrel was associated with a significantly increased risk of severe or moderate bleeding (HR 1.62, P=0.04) among current smokers but a smaller and nonsignificant increase among never-smokers (HR 1.31, P=0.15). CONCLUSIONS: Clopidogrel therapy may be more effective in current smokers, but it may also confer a greater bleeding risk than in nonsmokers. Further studies are needed to investigate this possibility
— id: 105924, year: 2009, vol: 120, page: 2337, stat: Journal Article,

Aspirin use, dose, and clinical outcomes in postmenopausal women with stable cardiovascular disease: the Women's Health Initiative Observational Study
Berger, Jeffrey S; Brown, David L; Burke, Gregory L; Oberman, Albert; Kostis, John B; Langer, Robert D; Wong, Nathan D; Wassertheil-Smoller, Sylvia
2009 Mar;2(2):78-87, Ciculation : Cardiovascular quality & outcomes
BACKGROUND: Despite compelling evidence that aspirin reduces fatal and nonfatal vascular events among the overall population in various settings, women have frequently been underrepresented and their data underreported. We sought to evaluate the relationship between aspirin use, dose (81 or 325 mg), and clinical outcomes among postmenopausal women with stable cardiovascular disease (CVD). METHODS AND RESULTS: Women with CVD (n=8928) enrolled in the Women's Health Initiative Observational Study were used for this analysis. The primary outcome was the incidence of all-cause mortality and cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Among 8928 women with stable CVD, 4101 (46%) reported taking aspirin, of whom 30% were on 81 mg and 70% were on 325 mg. At 6.5 years of follow-up, no significant association was noted for aspirin use and all-cause mortality or cardiovascular events. However, after multivariate adjustment, aspirin use was associated with a significantly lower all-cause (adjusted hazard ratio, 0.86 [0.75 to 0.99]; P=0.04) and cardiovascular-related mortality (adjusted hazard ratio, 0.75 [0.60 to 0.95]; P=0.01) compared with no aspirin. Aspirin use was associated with a lower risk of cardiovascular events (adjusted hazard ratio, 0.90 [0.78 to 1.04]; P=0.14), which did not meet statistical significance. Compared with 325 mg, use of 81 mg was not significantly different for all-cause mortality, cardiovascular events, or any individual end point. CONCLUSIONS: After multivariate adjustment, aspirin use was associated with significantly lower risk of all-cause mortality, specifically, cardiovascular mortality, among postmenopausal women with stable CVD. No significant difference was noted between 81 mg and 325 mg of aspirin. Overall, aspirin use was low in this cohort of women with stable CVD
— id: 106387, year: 2009, vol: 2, page: 78, stat: Journal Article,

Sex differences in mortality following acute coronary syndromes
Berger, Jeffrey S; Elliott, Laine; Gallup, Dianne; Roe, Matthew; Granger, Christopher B; Armstrong, Paul W; Simes, R John; White, Harvey D; Van de Werf, Frans; Topol, Eric J; Hochman, Judith S; Newby, L Kristin; Harrington, Robert A; Califf, Robert M; Becker, Richard C; Douglas, Pamela S
2009 Aug 26;302(8):874-882, JAMA
CONTEXT: Conflicting information exists about whether sex differences modulate short-term mortality following acute coronary syndromes (ACS). OBJECTIVES: To investigate the relationship between sex and 30-day mortality in ACS, and to determine whether this relationship was modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates. DESIGN, SETTING, AND PARTICIPANTS: A convenience sample of patients pooled from 11 independent, international, randomized ACS clinical trials between 1993 and 2006 whose databases are maintained at the Duke Clinical Research Institute, Durham, North Carolina. Of 136 247 patients, 38 048 (28%) were women; 102 004 (26% women) with ST-segment elevation myocardial infarction (STEMI), 14 466 (29% women) with non-STEMI (NSTEMI), and 19 777 (40% women) with unstable angina. MAIN OUTCOME MEASURE: Thirty-day mortality following ACS. RESULTS: Thirty-day mortality was 9.6% in women and 5.3% in men (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.83-2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR, 1.06; 95% CI, 0.99-1.15). A significant sex by type of ACS interaction was demonstrated (P < .001). In STEMI, 30-day mortality was higher among women (adjusted OR, 1.15; 95% CI, 1.06-1.24), whereas in NSTEMI (adjusted OR, 0.77; 95% CI, 0.63-0.95) and unstable angina, mortality was lower among women (adjusted OR, 0.55; 95% CI, 0.43-0.70). In a cohort of 35 128 patients with angiographic data, women more often had nonobstructive (15% vs 8%) and less often had 2-vessel (25% vs 28%) and 3-vessel (23% vs 26%) coronary disease, regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (P for interaction = .70). CONCLUSIONS: Sex-based differences existed in 30-day mortality among patients with ACS and vary depending on clinical presentation. However, these differences appear to be largely explained by clinical differences at presentation and severity of angiographically documented disease
— id: 101900, year: 2009, vol: 302, page: 874, stat: Journal Article,

Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials
Berger, Jeffrey S; Krantz, Mori J; Kittelson, John M; Hiatt, William R
2009 May 13;301(18):1909-1919, JAMA
CONTEXT: Randomized trials have shown that aspirin decreases the risk of cardiovascular events in patients with symptomatic coronary and cerebrovascular disease. Despite guideline recommendations for secondary prevention in peripheral artery disease (PAD), the effect of aspirin in this population is not well established. OBJECTIVE: To investigate the effect of aspirin on cardiovascular event rates in patients with PAD. DATA SOURCES AND STUDY SELECTION: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, Science Citation Index (1966 to December 2008), and unpublished studies from the supplemental index of the Antithrombotic Trialists' Collaboration. Eligible studies were prospective, randomized controlled trials of aspirin therapy, with or without dipyridamole that reported cardiovascular event rates. Eighteen trials involving 5269 individuals were identified. DATA EXTRACTION: Studies were reviewed to determine the number of participants, mean follow-up, and the primary end point of cardiovascular events (nonfatal myocardial infarction [MI], nonfatal stroke, and cardiovascular death). Data on the secondary end points of all-cause mortality, major bleeding, and the individual components of the primary outcome measure were also abstracted. For the primary end point, the analysis had 88% power to detect a 25% reduction and 70% power to detect a 20% reduction in cardiovascular events in the aspirin group compared with the control group. DATA SYNTHESIS: Among 5269 participants, cardiovascular events were experienced by 251 (8.9%) of 2823 patients taking aspirin (alone or with dipyridamole) and by 269 (11.0%) of 2446 in the control group (pooled relative risk [RR], 0.88; 95% confidence interval [CI], 0.76-1.04). Aspirin therapy was associated with a reduction in the secondary outcome of nonfatal stroke (52 of 2823 vs 76 of 2446; RR, 0.66; 95% CI, 0.47-0.94) but was not associated with significant reductions in all-cause or cardiovascular mortality, MI, or major bleeding. In the subset of 3019 participants taking aspirin alone vs control, aspirin was associated with a nonsignificant reduction in cardiovascular events (125 of 1516 vs 144 of 1503; RR, 0.75; 95% CI, 0.48-1.18), a significant reduction in nonfatal stroke (32 of 1516 vs 51 of 1503; RR, 0.64; 95% CI, 0.42-0.99), but no statistically significant reductions in all-cause or cardiovascular mortality, MI, or major bleeding. CONCLUSIONS: In patients with PAD, treatment with aspirin alone or with dipyridamole resulted in a statistically nonsignificant decrease in the primary end point of cardiovascular events and a significant reduction in nonfatal stroke. Results for the primary end point may reflect limited statistical power. Additional randomized controlled trials of aspirin therapy are needed to establish the net benefit and bleeding risks in PAD
— id: 101135, year: 2009, vol: 301, page: 1909, stat: Journal Article,

Reporting and representation of race/ethnicity in published randomized trials
Berger, Jeffrey S; Melloni, Chiara; Wang, Tracy Y; Dolor, Rowena J; Frazier, Camille G; Samad, Zainab; Peterson, Eric D; Mark, Daniel B; Newby, L Kristin
2009 Nov;158(5):742-747, American heart journal
BACKGROUND: Although adequate representation of specific subgroups (eg, women and the elderly) in randomized controlled trials (RCTs) has been under intense scrutiny, there are few data on representation by race. METHODS: Using all RCTs cited by the 2007 American Heart Association guidelines for cardiovascular disease prevention in women (although trials were included whether or not there were female participants), we explored the extent to which information on race was reported in the baseline characteristics. Race/ethnicity categories were whites, blacks, Asians, Hispanics, and 'others.' RESULTS: Overall, 156 trials were analyzed. Demographic data on race/ethnicity were reported in 55 (35%) trials and increased significantly over time (1970s, 12.5%; 1980s, 25%; 1990s, 30.5%; 2000s, 46.2%; P for trend = .011). Among the 55 trials reporting any race/ethnicity information, trial inclusion of whites, blacks, Asians, Hispanics, and 'others' was reported in 27%, 13%, 14%, 5%, and 10% of trials, respectively, and increased over time (P for trend < .05 for all). Trials enrolling subjects only in the United States or globally, including the US, were more likely to report race composition than trials that included no US sites (US only 64% vs global 62% vs non-US 21%, P < .01). Industry- and federal/foundation-funded RCTs reported race with similar frequency (industry 36% vs federal 34% vs both 24%, P = .44). When we isolated our analyses to trials that were funded by the National Institutes of Health, 12 (67%) of 18 RCTs reported race/ethnicity as a baseline characteristic. CONCLUSION: Although reporting the race/ethnic composition of study populations is increasing over time, two thirds of all RCTs supporting a recent American Heart Association () guideline failed to publish any information on race. A necessary first requirement in translating RCT evidence to patients of all races is information regarding racial demographics. Such information should be strongly encouraged in future publications
— id: 104902, year: 2009, vol: 158, page: 742, stat: Journal Article,

Vascular disease burden and in-hospital outcomes among patients undergoing percutaneous coronary intervention in New York State
Berger, Jeffrey S; Petersen, John L; Brown, David L
2009 Aug;2(4):317-322, Circulation: Cardiovascular Interventions
BACKGROUND: The presence of atherosclerosis in extracardiac vascular beds is associated with an increased risk of adverse cardiovascular outcomes among stable patients with coronary artery disease (CAD). However, there is little data regarding the impact of the presence and extent of vascular disease on outcomes in patients with CAD undergoing percutaneous coronary intervention. METHODS AND RESULTS: We analyzed 69,045 consecutive patients from the New York State Coronary Angioplasty Reporting System database who underwent percutaneous coronary intervention between 1998 and 1999. Vascular disease burden was assessed by history of aortoiliac, femoral-popliteal, and carotid disease. Patients were stratified into 3 groups: CAD alone, CAD and 1 additional site, and CAD and 2 or 3 additional sites. A logistic regression model was constructed to determine the relation between vascular disease burden and in-hospital mortality. Any history of vascular disease was present in 5915 (8.6%) of the population, of whom 4840 (82%) had CAD and 1 other disease location and 1075 (18%) had CAD and 2 or 3 other disease locations. There was a significant relationship between the number of disease locations and hospital mortality, ranging from 0.7% in patients with CAD alone to 2.0% and 2.6% for patients with 1 or >or =2 disease locations, respectively (P<0.001). In unadjusted analysis, in-hospital mortality was approximately 3-fold higher (odds ratio, 2.89; 95% CI, 2.31 to 3.60; P<0.001) and 4-fold higher (odds ratio, 3.78; 95% CI, 2.57 to 5.56; P<0.001) for inpatients with CAD and additional vascular disease at 1 site and > or =2 sites, respectively. After multivariable adjustment, each additional vascular bed affected was associated with a 50% increase in in-hospital mortality (odds ratio, 1.50; 95% CI, 1.27 to 1.78; P<0.001). CONCLUSIONS: Among patients with CAD undergoing percutaneous coronary intervention, vascular disease burden is associated with higher rates of adverse events and is an independent predictor of in-hospital mortality
— id: 106389, year: 2009, vol: 2, page: 317, stat: Journal Article,

Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rapid ReversAl of platelet thromboSis with intravenous Elinogrel before PCI to optimize reperfusion in acute Myocardial Infarction (ERASE MI) pilot trial
Berger, Jeffrey S; Roe, Matthew T; Gibson, C Michael; Kilaru, Rakhi; Green, Cynthia L; Melton, Laura; Blankenship, James D; Metzger, D Christopher; Granger, Christopher B; Gretler, Daniel D; Grines, Cindy L; Huber, Kurt; Zeymer, Uwe; Buszman, Pawel; Harrington, Robert A; Armstrong, Paul W
2009 Dec;158(6):998-1004.e1, American heart journal
BACKGROUND: Inhibition of the P2Y12 ADP-receptor with oral antiplatelet agents given to patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with improved outcomes, but this strategy is limited by the time required for maximal antiplatelet effect after administration. We examined the safety and tolerability of a novel, direct-acting, reversible, intravenous P2Y12 ADP-receptor antagonist, elinogrel, versus placebo when administered to STEMI patients before primary PCI. METHODS: The ERASE MI trial was a pilot, phase IIA, randomized, double-blind, placebo-controlled, dose-escalation study designed to evaluate the safety and tolerability of escalating doses (10, 20, 40, and 60 mg) of elinogrel administered as a single intravenous bolus before the start of the diagnostic angiogram preceding primary PCI. Patients were randomly assigned in a 1:1 manner to either elinogrel or placebo within each dosing group; and all patients received a 600-mg clopidogrel loading dose, followed by a second 300-mg clopidogrel loading dose 4 hours after PCI. The major outcome, in-hospital bleeding, was assessed with the Thrombolysis in Myocardial Infarction and Global Strategies to Open Occluded Coronary Arteries bleeding scales. Pre-PCI corrected Thrombolysis in Myocardial Infarction frame count and ST-segment resolution were also evaluated. RESULTS: Seventy patients were randomized in the dose-escalation study, but the dose-confirmation phase was not started because the trial was prematurely terminated for administrative reasons. The incidence of bleeding events was infrequent and appeared to be similar in patients treated with all doses of elinogrel versus placebo. No differences in serious adverse events, laboratory values, corrected Thrombolysis in Myocardial Infarction frame count, or ST resolution were demonstrated between elinogrel and placebo. CONCLUSIONS: With the limitations of a small study sample size, this pilot study provided preliminary data on the feasibility and tolerability of escalating doses of a direct-acting, reversible, intravenous P2Y12 ADP-receptor antagonist, elinogrel, as an adjunctive therapy for primary PCI for STEMI
— id: 106385, year: 2009, vol: 158, page: 998, stat: Journal Article,

Amiodarone for the prevention of sudden cardiac death: a meta-analysis of randomized controlled trials
Piccini, Jonathan P; Berger, Jeffrey S; O'Connor, Christopher M
2009 May;30(10):1245-1253, European heart journal
AIMS: Not all patients at risk for sudden cardiac death (SCD) are eligible for, or have access to implantable cardioverter defibrillator (ICD) implantation. There are conflicting data regarding the efficacy and safety of amiodarone for the prevention of SCD. METHODS AND RESULTS: We conducted a meta-analysis of all randomized controlled trials examining the use of amiodarone vs. placebo/control for the prevention of SCD. We identified 15 trials, which randomized 8522 patients to amiodarone or placebo/control. Amiodarone decreased the incidence of SCD [7.1 vs. 9.7%; OR 0.71 (0.61-0.84), P < 0.001] and cardiovascular death (CVD) [14.0 vs. 16.3%; OR 0.82 (0.71-0.94), P = 0.004]. There was a 1.5% absolute risk reduction in all-cause mortality which did not meet statistical significance (P = 0.093). Amiodarone therapy increased the risk of pulmonary [2.9 vs. 1.5%; OR 1.97, (1.27-3.04), P = 0.002], and thyroid [3.6 vs. 0.4%; OR 5.68, (2.94-10.98), P < 0.001] toxicity. CONCLUSION: Amiodarone reduces the risk of SCD by 29% and CVD by 18%, and therefore, represents a viable alternative in patients who are not eligible for or who do not have access to ICD therapy for the prevention of SCD. However, amiodarone therapy is neutral with respect to all-cause mortality and is associated with a two- and five-fold increased risk of pulmonary and thyroid toxicity
— id: 101136, year: 2009, vol: 30, page: 1245, stat: Journal Article,

Impact of left ventricular dysfunction on hospital mortality among patients undergoing elective percutaneous coronary intervention
Wallace, Thomas W; Berger, Jeffrey S; Wang, Andrew; Velazquez, Eric J; Brown, David L
2009 Feb 1;103(3):355-360, American journal of cardiology
Many patients with systolic dysfunction undergo elective percutaneous coronary intervention (PCI) despite the unknown risk and limited data supporting its use. Therefore, the aim of this study was to evaluate the association between the severity of left ventricular (LV) systolic dysfunction and hospital mortality in patients who undergo elective PCI. A retrospective cohort study was conducted of all patients who underwent elective PCI in New York State in 1998 and 1999. Patients were stratified into 5 groups on the basis of their LV ejection fractions (EFs) before PCI (>55%, 46% to 55%, 36% to 45%, 26% to 35%, and < or =25%). Comparisons of demographic, procedural, and outcome variables were performed, and adjusted odds ratios (ORs) were calculated to evaluate the relation between the EF and hospital mortality. Among 55,709 patients who underwent elective PCI, EFs < or =25%, 26% to 35% and 36% to 45% were present in 3.4%, 7.6%, and 17.4%, respectively. Hospital mortality was 0.3%, 0.2%, 0.6%, 1.2%, and 2.7% in the groups with EFs >55%, 46% to 55%, 36% to 45%, 26% to 35%, and < or =25%, respectively (p <0.001). After multivariate adjustment, an increased risk for hospital mortality was significant for EF groups of 36% to 45% (OR 1.56, 95% confidence interval 1.06 to 2.30), 26% to 35% (OR 2.17, 95% confidence interval 1.42 to 3.31), and < or =25% (OR 3.85, 95% confidence interval 2.46 to 6.01) compared with EF >55%, respectively. In conclusion, this analysis demonstrates that elective PCI is commonly performed in patients with reduced EFs, and the risk for hospital mortality increases as the EF decreases. For patients who undergo elective PCI, an EF < or =45% is associated with higher adjusted hospital mortality. Whether elective PCI in patients with low EFs reduces morbidity and/or mortality over medical therapy alone is unknown
— id: 101137, year: 2009, vol: 103, page: 355, stat: Journal Article,

Highlights from American Heart Association, November 4-7, 2007, Orlando, Florida, USA. Late-breaking trials summary
Allen, Larry A; Jolicoeur, E Marc; Melloni, Chiara; Lopes, Renato D; Chan, Mark Y; Majidi, Mohamed; Piccini, Jonathan P; Berger, Jeffrey S; Katz, Jason N; Shah, Bimal R
2008 Apr;155(4):615-623, American heart journal
— id: 101141, year: 2008, vol: 155, page: 615, stat: Journal Article,

Improving the quality of care for women with cardiovascular disease: report of a DCRI Think Tank, March 8 to 9, 2007
Berger, Jeffrey S; Bairey-Merz, C Noel; Redberg, Rita F; Douglas, Pamela S
2008 Nov;156(5):816-25, 825.e1, American heart journal
BACKGROUND: Differences in pathophysiology, diagnosis, and treatment of women with cardiovascular disease compared with men has become a major focus during the past decade. Nevertheless, little attention has focused on improving the quality of healthcare in women compared with other areas of cardiovascular medicine. METHODS: To address this deficit, Duke University Medical Center convened a national Duke Clinical Research Institute (DCRI) Think Tank meeting, including basic science and clinical researchers, payers, legislators, clinical experts, government regulators, and members of the pharmaceutical and device industries. This report provides an overview of the discussions and proposed solutions. RESULTS: Discussion concentrated on the development of strategies to improve the quality of health care for women with heart disease. Key components to improve quality care include: (1) enhance the quantity and quality of evidence-based medicine to guide care in women through improvements in trial design, enrollment and retention of women subjects, results analysis and reporting, and better incentives to perform research in women; (2) provide incentives to develop better data in women through mandating changes in the drug and device development and approval processes; (3) incorporate specific recommendations for women into guidelines when data are sufficient; and (4) apply proven sex-based differences in risk stratification, diagnostic testing, and drug usage and dosing in clinical care. Examples of possible strategies are included. CONCLUSION: The above approach represents a necessary, but not sufficient, platform to improve the overall quality of healthcare in women with cardiovascular disease
— id: 101138, year: 2008, vol: 156, page: 816, stat: Journal Article,

Impact of clopidogrel in patients with acute coronary syndromes requiring coronary artery bypass surgery: a multicenter analysis
Berger, Jeffrey S; Frye, Carla B; Harshaw, Qing; Edwards, Fred H; Steinhubl, Steven R; Becker, Richard C
2008 Nov 18;52(21):1693-1701, Journal of the American College of Cardiology
OBJECTIVES: The purpose of our multicenter study was to examine the impact of pre-operative administration of clopidogrel on reoperation rates, incidence of life-threatening bleeding, inpatient length of stay, and other bleeding-related outcomes in acute coronary syndrome (ACS) patients requiring cardiopulmonary bypass (coronary artery bypass graft surgery [CABG]) in a broad cross section of U.S. hospitals. BACKGROUND: There is relative uncertainty about the relationship between clopidogrel and CABG-associated outcomes in the setting of ACS. METHODS: A retrospective cohort analysis was performed of randomly selected ACS patients requiring CABG in 14 hospitals across the U.S. Patients exposed to clopidogrel were compared with those not exposed to clopidogrel within 5 days prior to surgery. RESULTS: Of the 596 patients enrolled in the study, 298 had been exposed to clopidogrel within 5 days (Group A). Patients in Group A were more than 3-fold more likely to require reoperation for assessment of bleeding than patients not exposed to clopidogrel (6.4% vs. 1.7% Group B, p = 0.004). Major bleeding occurred in 35% of Group A patients versus 26% of Group B patients (p = 0.049). Length of stay was greater in Group A compared with Group B (9.7 +/- 6.0 days vs. 8.6 +/- 4.7 days, unadjusted p = 0.016). After logistic regression analysis, clopidogrel exposure within 5 days of CABG was the strongest predictor of reoperation (odds ratio [OR]: 4.60, 95% confidence interval [CI]: 1.45 to 14.55) and major bleeding (OR: 1.824, 95% CI: 1.106 to 3.008). CONCLUSIONS: After ACS, patients who undergo CABG within 5 days of receiving clopidogrel are at increased risk for reoperation, major bleeding, and increased length of stay. These risks must be balanced by the clinical benefits of clopidogrel use demonstrated in randomized clinical trials
— id: 101139, year: 2008, vol: 52, page: 1693, stat: Journal Article,

Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy
Berger, Jeffrey S; Stebbins, Amanda; Granger, Christopher B; Ohman, Eric M; Armstrong, Paul W; Van de Werf, Frans; White, Harvey D; Simes, R John; Harrington, Robert A; Califf, Robert M; Peterson, Eric D
2008 Jan 15;117(2):192-199, Circulation
BACKGROUND: Although treatment with immediate aspirin reduces morbidity and mortality in ST-elevation myocardial infarction, the optimal dose is unclear. We therefore compared the acute mortality and bleeding risks associated with the initial use of 162 versus 325 mg aspirin in fibrinolytic-treated ST-elevation myocardial infarction patients. METHODS AND RESULTS: Using combined data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) trials (n=48 422 ST-elevation myocardial infarction patients), we compared the association between initial aspirin dose of 162 versus 325 mg and 24-hour and 7-day mortality, as well as rates of in-hospital moderate/severe bleeding. Results were adjusted for previously identified mortality and bleeding risk factors. Overall, 24.4% of patients (n=11 828) received an initial aspirin dose of 325 mg, and 75.6% (n=36 594) received 162 mg. The 24-hour mortality rates were 2.9% versus 2.8% (P=0.894) for those receiving an initial aspirin dose of 325 versus 162 mg. Mortality rates at 7 and 30 days were 5.2% versus 4.9% (P=0.118) and 7.1% versus 6.5% (P=0.017) among patients receiving the 325 versus 162 mg aspirin. After adjustment, aspirin dose was not associated with 24-hour (odds ratio [OR], 1.01; 95% CI, 0.82 to 1.25), 7-day (OR, 1.00; 95% CI, 0.87 to 1.17), or 30-day (OR, 0.99; 95% CI, 0.87 to 1.12) mortality rates. No significant difference was noted for myocardial infarction or the composite of death or myocardial infarction between groups. In-hospital moderate/severe bleeding occurred in 9.3% of those treated with 325 mg versus 12.2% among those receiving 162 mg (P<0.001). After adjustment, 325 mg was associated with a significant increase in moderate/severe bleeding (OR, 1.14; 95% CI, 1.05 to 1.24; P=0.003). CONCLUSIONS: These data suggest that an initial dose of 162 mg aspirin may be as effective as and perhaps safer than 325 mg for the acute treatment of ST-elevation myocardial infarction
— id: 101143, year: 2008, vol: 117, page: 192, stat: Journal Article,

Early sustained ventricular arrhythmias complicating acute myocardial infarction
Piccini, Jonathan P; Berger, Jeffrey S; Brown, David L
2008 Sep;121(9):797-804, American journal of medicine
OBJECTIVE: Sustained ventricular arrhythmias complicate 2% to 20% of acute myocardial infarctions (MIs) and are associated with increased in-hospital mortality. However, it remains unclear whether successful mechanical revascularization improves outcomes in these patients. The objective of this analysis was to identify predictors of sustained ventricular arrhythmias after acute MI and to determine the influence of successful revascularization on in-hospital mortality. METHODS: We conducted a retrospective cohort study of all patients who underwent percutaneous coronary intervention for acute MI in New York State between 1997 and 1999. RESULTS: Of the 9015 patients who underwent percutaneous coronary intervention for acute MI, 472 (5.2%) developed sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) before revascularization. After multivariable adjustment, independent predictors of sustained VT/VF included cardiogenic shock (odds ratio [OR], 4.10; 95% confidence interval [CI], 3.20-5.58; P <.001), heart failure (OR, 2.86; 95% CI, 2.24-3.67: P <.001), chronic kidney disease (OR, 2.58; 95% CI, 1.27-5.23; P=.009), and presentation within 6 hours of symptom onset (OR, 1.46; 95% CI, 1.18-1.81; P=.001). Patients with sustained VT/VF had greater in-hospital mortality (16.3% vs 3.7%, P <.001). Although successful percutaneous coronary intervention was associated with decreased in-hospital mortality in patients with VT/VF (P <.001), patients with sustained VT/VF and successful revascularization experienced increased mortality compared with patients without sustained ventricular arrhythmias (P <.001). CONCLUSION: Among patients undergoing percutaneous coronary intervention for acute MI, sustained VT/VF remains a significant complication associated with a 4-fold increased risk of in-hospital mortality. Early mortality is reduced after successful percutaneous coronary intervention, but remains elevated in this high-risk group
— id: 101140, year: 2008, vol: 121, page: 797, stat: Journal Article,

Lipoprotein-associated phospholipase A2, hormone use, and the risk of ischemic stroke in postmenopausal women
Wassertheil-Smoller, Sylvia; Kooperberg, Charles; McGinn, Aileen P; Kaplan, Robert C; Hsia, Judith; Hendrix, Susan L; Manson, JoAnn E; Berger, Jeffrey S; Kuller, Lewis H; Allison, Matthew A; Baird, Alison E
2008 Apr;51(4):1115-1122, Hypertension
Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA(2)) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA(2) and stroke. We assessed the relationship between Lp-PLA(2) and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study from the Women's Health Initiative Observational Study. Mean (SD) levels of Lp-PLA(2) were significantly higher among case subjects (309.0 [97.1]) than control subjects (296.3 [87.3]; P<0.01). Odds ratio for ischemic stroke for the highest quartile of Lp-PLA(2), compared with lowest, controlling for multiple covariates, was 1.08 (95% CI: 0.75 to 1.55). However, among 1137 nonusers of hormone therapy at baseline, the corresponding odds ratio was 1.55 (95% CI: 1.05 to 2.28),whereas there was no significant association among 737 hormone users (odds ratio: 0.70; 95% CI: 0.42 to 1.17; P for interaction=0.055). Moreover, among nonhormone users, women with high C-reactive protein and high Lp-PLA2 had more than twice the risk of stroke (odds ratio: 2.26; 95% CI: 1.55 to 3.35) compared with women low levels in both biomarkers. Furthermore, different stroke cases were identified as high risk by Lp-PLA(2) rather than by C-reactive protein. Lp-PLA(2) was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA(2)
— id: 101142, year: 2008, vol: 51, page: 1115, stat: Journal Article,

Vulnerable plaque : implications for the physician
Berger JS; Petersen JL; Tcheng J; Phillips HR
2007 ;2:721-731, Future cardiology
— id: 105332, year: 2007, vol: 2, page: 721, stat: Journal Article,

Gender disparity in failure rate for arterial catheter attempts
Eisen, Lewis A; Minami, Taro; Berger, Jeffrey S; Sekiguchi, Hiroshi; Mayo, Paul H; Narasimhan, Mangala
2007 May-Jun;22(3):166-172, Journal of intensive care medicine
We examined risk factors associated with failure of arterial catheterization in the medical intensive care unit of a large urban teaching hospital. We analyzed 92 consecutive arterial catheterizations by internal medicine house staff and critical care fellows. Of the 92 attempts, 26.1% were done on femoral arteries, and 73.9% were done on radial arteries. Failure, which occurred in 28% of attempts, was more common in female patients (P < .001). The failure rate was 50.0% for attempts on femoral arteries and 20.6% on radial arteries. Systolic blood pressure was significantly lower in patients where the attempt failed (P = .024). In univariate analyses, hemoglobin values were lower (P = .028) and number of percutaneous punctures were higher (P = .019) in patients where catheterization failed. After multivariate analysis, only gender and systolic blood pressure remained statistically significant. The strongest predictor of failure was female gender. A possible explanation not explored here could be smaller arterial size in female patients
— id: 101144, year: 2007, vol: 22, page: 166, stat: Journal Article,

Gender disparity in radial and femoral arterial size: an ultrasound study
Minami, Taro; Eisen, Lewis A; Berger, Jeffrey S; Sekiguchi, Hiroshi; Mayo, Paul H; Narasimhan, Mangala
2007 Mar;33(3):552-553, Intensive care medicine
— id: 101147, year: 2007, vol: 33, page: 552, stat: Journal Article,

Association of glycoprotein IIb/IIIa inhibitors and long-term survival following administration during percutaneous coronary intervention for acute myocardial infarction
Berger, Jeffrey S; Brown, David L
2006 Jun;21(3):229-234, Journal of thrombosis & thrombolysis
OBJECTIVES: We sought to evaluate the impact of GP IIb/IIIa receptor blockers on long-term mortality in patients undergoing PCI for AMI. BACKGROUND: Glycoprotein (GP) IIb/IIIa inhibitors are potent suppressors of platelet aggregation and when used during percutaneous coronary intervention (PCI) for the treatment of acute myocardial infarction (AMI) may improve short-term clinical outcomes, including survival. However, the impact of GP IIb/IIIa treatment during PCI for AMI on long-term survival is unknown. METHODS: Patients undergoing primary or rescue PCI for AMI within 24 hours of symptom onset with or without GP IIb/IIIa inhibitor treatment were identified from a multicenter PCI database. All cause mortality at a mean follow-up of 3 years was the primary end point. RESULTS: Of the 269 patients treated with primary or rescue PCI for AMI, 107 (40%) received a GP IIb/IIIa antagonist. Patients treated with GP inhibitors were more likely to present with or develop heart failure (13% vs. 6.2%, P = 0.052). Left ventricular ejection fraction was reduced in those treated with GP IIb/IIIa antagonists (44% vs. 48%, P = 0.051). The extent of coronary artery disease did not differ between groups. Stent use was 80% in both groups. Procedural success was high and did not differ between groups. In-hospital mortality was low and did not differ between groups. The mortality at a mean follow-up of 3 years was 1.9% among patients treated with a GP IIb/IIIa antagonist and 15% for those who were not treated (log-rank P = 0.0005). Treatment with a GP IIb/IIIa antagonist was independently associated with a significant reduction in the hazard of long-term mortality (Hazard Ratio, 0.159; 95% Confidence Interval, 0.034-0.729; P = 0.018). CONCLUSIONS: Treatment of patients undergoing PCI for AMI with GP IIb/IIIa antagonists appears to be associated with a profound reduction in late mortality
— id: 101148, year: 2006, vol: 21, page: 229, stat: Journal Article,

Gender-age interaction in early mortality following primary angioplasty for acute myocardial infarction
Berger, Jeffrey S; Brown, David L
2006 Nov 1;98(9):1140-1143, American journal of cardiology
Previous studies have demonstrated a significant interaction between gender and age after medically treated acute myocardial infarction (AMI), when younger women were found to have a higher mortality rate than younger men, but the mortality rate for older men and women was similar. The study objective was to determine whether a gender-age interaction exists for AMI treated exclusively with primary angioplasty. This analysis was a retrospective cohort study of 9,015 consecutive patients who underwent primary angioplasty for AMI in New York State from 1997 to 1999. The primary end point of interest was in-hospital mortality. A logistic regression model was constructed to determine the relation between gender and mortality among patients with AMI treated with angioplasty. Additional analyses were performed to test whether a mortality difference existed according to age. In-hospital mortality rate was twofold higher in women than in men (6.7% vs 3.4%, p <0.001). After adjusting for age, co-morbid conditions, and hemodynamic status by multivariable logistic regression analysis, the odds ratio for in-hospital death for women was no longer significant (odds ratio 1.21, 95% confidence interval 0.69 to 2.10, p = 0.51). Among patients <75 years of age, women had a 37% increased risk of in-hospital mortality (adjusted odds ratio 1.37, 95% confidence interval 1.01 to 1.98, p = 0.04), whereas there was no significant difference in mortality between men and women who were >or=75 years of age. In conclusion, female gender was found to be an independent predictor of in-hospital mortality in patients <75 years of age after primary angioplasty for AMI
— id: 101145, year: 2006, vol: 98, page: 1140, stat: Journal Article,

Comparison of outcomes in acute myocardial infarction treated with coronary angioplasty alone versus coronary stent implantation
Berger, Jeffrey S; Fridman, Vladimir; Brown, David L
2006 Apr 1;97(7):977-980, American journal of cardiology
Randomized trials have demonstrated the superiority of primary angioplasty with stent implantation over balloon angioplasty alone in the treatment of acute myocardial infarction (AMI). However, it remains unknown whether the beneficial outcomes that are attained in clinical trials can be generalized to community-based practice. We conducted a retrospective cohort study of all patients who underwent primary angioplasty for AMI in New York State in 1998 and 1999. In total, 6,010 consecutive patients who presented within 23 hours of an AMI were identified for this analysis. In-hospital mortality was the primary end point. Stents were placed in 5,225 patients (87%). Patients who received stents were younger (61 vs 62 years, p = 0.011) and less often women (29% vs 33%, p = 0.018). Patients who received stents were less likely to have a history of hypertension (56% vs 61%, p = 0.013), diabetes (17% vs 24%, p <0.001), a creatinine level > or = 2.5 mg/dl (0.8% vs 2.0%, p = 0.002), 3-vessel coronary disease (14% vs 19%, p <0.001), and left main disease (2.4% vs 4.6%, p <0.001). Stent use was associated with significant decreases in length of stay (5.9 vs 8.1 day, p <0.001), major adverse cardiovascular events (4.1% vs 12%, p <0.001), and in-hospital mortality (3.5% vs 9.3%, p <0.001). After multivariate logistic regression analysis to adjust for differences in baseline characteristics, stent use was associated with a 50% decrease in risk of in-hospital mortality (odds ratio 0.474, 95% confidence interval 0.311 to 0.723, p = 0.001)
— id: 101150, year: 2006, vol: 97, page: 977, stat: Journal Article,

Clinical implications of vulnerable plaque
Berger, Jeffrey S; Petersen, John L; Tcheng, James E; Phillips, Harry R
2006 Nov;2(6):721-731, Future cardiology
In many individuals, the first indicator of atherosclerosis is an acute heart attack, which is often fatal. Despite innovations in medical therapy and interventional cardiology techniques, coronary artery disease continues to be the leading cause of death in the USA. There is great interest in identifying vulnerable plaques and vulnerable patients as a possible means to stem the tide against coronary artery disease. Improvements in diagnostic studies and development of novel imaging tools have opened the possibilities for significant advances in the management of vulnerable plaque. The result of improved risk stratification, by both noninvasive and invasive means, will be a better assessment of the risk/benefit relationships for the novel therapies that are needed to further reduce the morbidity and mortality of the disease. Correct identification of vulnerable plaque would permit the use of more effective systemic treatment and enable clinical trials to study the supplemental benefit from local treatments
— id: 105330, year: 2006, vol: 2, page: 721, stat: Journal Article,

Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials
Berger, Jeffrey S; Roncaglioni, Maria C; Avanzini, Fausto; Pangrazzi, Ierta; Tognoni, Gianni; Brown, David L
2006 Jan 18;295(3):306-313, JAMA
CONTEXT: Aspirin therapy reduces the risk of cardiovascular disease in adults who are at increased risk. However, it is unclear if women derive the same benefit as men. OBJECTIVE: To determine if the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease vary by sex. DATA SOURCES AND STUDY SELECTION: MEDLINE and the Cochrane Central Register of Controlled Trials databases (1966 to March 2005), bibliographies of retrieved trials, and reports presented at major scientific meetings. Eligible studies were prospective, randomized controlled trials of aspirin therapy in participants without cardiovascular disease that reported data on myocardial infarction (MI), stroke, and cardiovascular mortality. Six trials with a total of 95 456 individuals were identified; 3 trials included only men, 1 included only women, and 2 included both sexes. DATA EXTRACTION: Studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points (a composite of cardiovascular events [nonfatal MI, nonfatal stroke, and cardiovascular mortality], each of these individual components separately, and major bleeding). DATA SYNTHESIS: Among 51,342 women, there were 1285 major cardiovascular events: 625 strokes, 469 MIs, and 364 cardiovascular deaths. Aspirin therapy was associated with a significant 12% reduction in cardiovascular events (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.79-0.99; P = .03) and a 17% reduction in stroke (OR, 0.83; 95% CI, 0.70-0.97; P = .02), which was a reflection of reduced rates of ischemic stroke (OR, 0.76; 95% CI, 0.63-0.93; P = .008). There was no significant effect on MI or cardiovascular mortality. Among 44,114 men, there were 2047 major cardiovascular events: 597 strokes, 1023 MIs, and 776 cardiovascular deaths. Aspirin therapy was associated with a significant 14% reduction in cardiovascular events (OR, 0.86; 95% CI, 0.78-0.94; P = .01) and a 32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P = .001). There was no significant effect on stroke or cardiovascular mortality. Aspirin treatment increased the risk of bleeding in women (OR, 1.68; 95% CI, 1.13-2.52; P = .01) and in men (OR, 1.72; 95% CI, 1.35-2.20; P<.001). CONCLUSIONS: For women and men, aspirin therapy reduced the risk of a composite of cardiovascular events due to its effect on reducing the risk of ischemic stroke in women and MI in men. Aspirin significantly increased the risk of bleeding to a similar degree among women and men
— id: 101151, year: 2006, vol: 295, page: 306, stat: Journal Article,

Influence of sex on in-hospital outcomes and long-term survival after contemporary percutaneous coronary intervention
Berger, Jeffrey S; Sanborn, Timothy A; Sherman, Warren; Brown, David L
2006 May;151(5):1026-1031, American heart journal
BACKGROUND: Early studies suggested that morbidity and mortality after percutaneous coronary intervention (PCI) were greater for women than men. However, in recent reports, sex-related differences in short-term outcome have decreased as outcomes among women have improved. OBJECTIVE: The aim of the study was to evaluate the effect of sex on long-term mortality among a large cohort of patients undergoing PCI in the contemporary era. METHODS: Three hospitals in New York City contributed prospectively defined data elements on 4284 consecutive patients undergoing PCI in 1998 to 1999. All-cause mortality at a mean follow-up of 3 years was the primary end point. RESULTS: Of the 4284 patients, 1331 (31%) were women. Women were significantly older than men (mean age 67 vs 62 years, P < .001) and less often white (72% vs 80%, P < .001). Hypertension (78% vs 66%, P < .001) and diabetes (36% vs 22%, P < .001) were more prevalent in women. Prior cardiac surgery (14% vs 19%, P = .001) and previous myocardial infarction (MI) (33% vs 36%, P = .08) were less common among women. Presentation with unstable angina was more frequent in women (45% vs 41%, P = .034), whereas presentation with acute MI did not differ by sex. Congestive heart failure developed more commonly among women (7.1% vs 4.1%, P < .001). The extent of coronary disease (1-, 2-, or 3-vessel disease) did not differ between women and men. Mean ejection fraction was 52% in women and 50% in men (P < .001). Stents were placed in 77% of both groups. Procedural success was 97% for both women and men. Inhospital adverse outcomes including death, post-PCI MI, emergency bypass surgery, abrupt closure, and stent thrombosis were uncommon and not different between groups. Mortality at 3 years was 10% for women and 8.9% for men (P = .197). However, using Cox proportional hazards analysis to adjust for comorbidities and possible confounders, female sex was associated with a significant independent reduction in the hazard of long-term mortality (hazard ratio 0.78, 95% CI 0.620-0.969, P = .02). CONCLUSIONS: Despite more high-risk characteristics, female sex conferred a long-term survival advantage after PCI
— id: 101149, year: 2006, vol: 151, page: 1026, stat: Journal Article,

Mechanical complications of central venous catheters
Eisen, Lewis A; Narasimhan, Mangala; Berger, Jeffrey S; Mayo, Paul H; Rosen, Mark J; Schneider, Roslyn F
2006 Jan-Feb;21(1):40-46, Journal of intensive care medicine
We analyzed 385 consecutive central venous catheter (CVC) attempts over a 6-month period. All critically ill patients 18 years of age or older requiring a CVC were included. The rate of mechanical complications not including failure to place was 14%. Complications included failure to place the CVC (n = 86), arterial puncture (n = 18), improper position (n = 14), pneumothorax (n = 5 in 258 subclavian and internal jugular attempts), hematoma (n = 3), hemothorax (n = 1), and asystolic cardiac arrest of unknown etiology (n = 1). Male patients had a significantly higher complication rate than female patients (37% vs 27%, P = .04). The subclavian approach had a higher complication rate than the internal jugular or the femoral approach (39% vs 33% vs. 24%, P = .02). The complication rate increased with the number of percutaneous punctures, with a rate of 54% when more than 2 punctures were required
— id: 101146, year: 2006, vol: 21, page: 40, stat: Journal Article,

Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials
Andraws, Richard; Berger, Jeffrey S; Brown, David L
2005 Jun 1;293(21):2641-2647, JAMA
CONTEXT: Although Chlamydia pneumoniae infection has been associated with the initiation and progression of atherosclerosis, results of clinical trials investigating antichlamydial antibiotics as adjuncts to standard therapy in patients with coronary artery disease (CAD) have been inconsistent. OBJECTIVE: To conduct a meta-analysis of clinical trials of antichlamydial antibiotic therapy in patients with CAD. DATA SOURCES: The MEDLINE and Cochrane Central Register of Controlled Trials databases were searched from 1966 to April 2005 for English-language trials of antibiotic therapy in patients with CAD. Bibliographies of retrieved articles were searched for further studies. Presentations at major scientific meetings (2003-2004) were also reviewed. Search terms included antibacterial agents, myocardial infarction, unstable angina, and coronary arteriosclerosis. STUDY SELECTION: Eligible studies were prospective, randomized, placebo-controlled trials of antichlamydial antibiotic therapy in patients with CAD that reported all-cause mortality, myocardial infarction, or unstable angina. Of the 110 potentially relevant articles identified, 11 reports enrolling 19,217 patients were included. DATA EXTRACTION: Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points. End points of interest included all-cause mortality, myocardial infarction (MI), and a combined end point of MI and unstable angina. DATA SYNTHESIS: Event rates were combined using a random-effects model. Antibiotic therapy had no impact on all-cause mortality among treated vs untreated patients (4.7% vs 4.6%; odds ratio [OR], 1.02; 95% confidence interval [CI], 0.89-1.16; P = .83), on the rates of MI (5.0% vs 5.4%; OR, 0.92; 95% CI, 0.81-1.04; P = .19), or on the combined end point of MI and unstable angina (9.2% vs 9.6%; OR, 0.91; 95% CI, 0.76-1.07; P = .25). CONCLUSION: Evidence available to date does not demonstrate an overall benefit of antibiotic therapy in reducing mortality or cardiovascular events in patients with CAD
— id: 101153, year: 2005, vol: 293, page: 2641, stat: Journal Article,

Retrograde cerebral perfusion: report of a fatal complication from a subarachnoid venous hemorrhage during thoracoabdominal aortic surgery
Berger, Jeffrey S; Ryjikov, Natalia; Girardi, Leonard N; Fontes, Manuel L
2005 Oct;19(5):650-653, Journal of cardiothoracic & vascular anesthesia
— id: 101152, year: 2005, vol: 19, page: 650, stat: Journal Article,

Impact of platelet glycoprotein IIb/IIIa inhibitor therapy on in-hospital outcomes and long-term survival following percutaneous coronary rotational atherectomy
Berger, Jeffrey S; Slater, James N; Sherman, Warren; Green, Stephen J; Sanborn, Timothy A; Brown, David L
2005 Feb;19(1):47-54, Journal of thrombosis & thrombolysis
BACKGROUND: Percutaneous coronary rotational atherectomy (PCRA) is a potent stimulus of platelet activation and aggregation in vivo. For this reason, many patients undergoing PCRA are treated with platelet glycoprotein (GP) IIb/IIIa inhibitors. However, there is limited data regarding the ability of GP IIb/IIIa inhibitors to reduce ischemic complications of PCRA and no data regarding their effect on long-term survival. METHODS: Data on 1138 consecutive patients undergoing PCRA in 5 hospitals in 1998-1999 were pooled and analyzed. Long-term survival was available for all 530 patients treated in 3 of the hospitals. RESULTS AND CONCLUSIONS: GP IIb/IIIa inhibitors were administered to 315 of 1138 (28%) PCRA patients. There was no difference in age, gender or race among patients treated with and without GP IIb/IIIa antagonists. The prevalence of hypertension, diabetes, renal insufficiency and peripheral vascular disease did not differ between groups. Unstable angina was more common among patients treated with GP IIb/IIIa inhibitors (45% vs. 38%, P = 0.036) Patients treated with GP IIb/IIIa inhibitors had lower ejection fractions (50% vs. 55%, P < 0.001) and more 3-vessel coronary disease (24% vs. 16%, P = 0.002). Angiographic success was over 99% in both groups (P = NS). The frequency of major adverse cardiovascular events (MACE) was slightly greater in GP IIb/IIIa inhibitor treated patients (3.8% vs. 2.2%, P = 0.126). At a mean follow-up of 3 years, mortality was 13.3% in the GP IIb/IIIa treated patients and 12% in the untreated patients (P = 0.224). On Cox proportional hazards analysis, treatment with a GP IIb/IIIa inhibitor was not significantly associated with increased survival (Hazard Ratio, 0.81, 95% Confidence Interval, 0.631-1.039, P = 0.098). These data do not indicate a significant association between GP IIb/IIIa inhibitor treatment during PCRA and MACE or survival. CONDENSED ABSTRACT: There is limited data regarding the ability of GP IIb/IIIa inhibitors to reduce ischemic complications of percutaneous coronary rotational atherectomy (PCRA) and no data regarding their effect on long-term survival. These data do not indicate a significant association between GP IIb/IIIa inhibitor treatment during PCRA and MACE or survival
— id: 94800, year: 2005, vol: 19, page: 47, stat: Journal Article,

Impact of gender on mortality following primary angioplasty for acute myocardial infarction
Berger, Jeffrey S; Brown, David L
2004 Jan-Feb;46(4):297-304, Progress in cardiovascular diseases
— id: 101156, year: 2004, vol: 46, page: 297, stat: Journal Article,

Comparison of three-year outcomes in blacks versus whites with coronary heart disease following percutaneous coronary intervention
Berger, Jeffrey S; Sanborn, Timothy A; Sherman, Warren; Brown, David L
2004 Sep 1;94(5):647-649, American journal of cardiology
There are limited data regarding the effect of race on survival after percutaneous coronary intervention (PCI) in the modern era. The investigators analyzed the impact of race on 3-year survival in 3,783 consecutive patients who underwent PCI in 1998 and 1999
— id: 101155, year: 2004, vol: 94, page: 647, stat: Journal Article,

Effect of chronic obstructive pulmonary disease on survival of patients with coronary heart disease having percutaneous coronary intervention
Berger, Jeffrey S; Sanborn, Timothy A; Sherman, Warren; Brown, David L
2004 Sep 1;94(5):649-651, American journal of cardiology
There are limited data regarding the effect of chronic obstructive pulmonary disease (COPD) on the survival of patients with coronary artery disease. Prospectively developed and collected data elements on 4,284 consecutive patients who underwent percutaneous coronary intervention in 3 hospitals in 1998 and 1999 were pooled and analyzed. In-hospital major adverse cardiac outcomes were not different between groups. At 3-year follow-up, mortality for patients with COPD was 21% versus 9% for patients without COPD (log-rank p < 0.001). COPD was independently associated with a 2-fold increase in the hazard of long-term mortality (hazard ratio 2.146, 95% confidence interval 1.525 to 3.021, p < 0.001)
— id: 101154, year: 2004, vol: 94, page: 649, stat: Journal Article,