Marc A Pfeffer

Harvard Medical School, Boston, Massachusetts, United States

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Publications (538)5941.92 Total impact

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    ABSTRACT: The number of patients presenting with an acute myocardial infarction (MI) and prior coronary artery bypass grafting (CABG) is increasing. We compared the baseline characteristics, treatment, and clinical outcomes of patients with and without prior CABG in the VALIANT trial. Of the 14 703 patients with heart failure (HF), left ventricular systolic dysfunction, or both enrolled in VALIANT, 1026 (7%) had prior CABG. Prior CABG patients were older [mean age (SD): 67 (10) vs. 65 (12) years; P < 0.0001], had more comorbidity, and more frequent non-Q wave MI (66 vs. 30%; P < 0.0001). At hospital presentation, prior CABG patients received less aspirin (82 vs. 90%; P < 0.0001) and thrombolysis (21 vs. 36%; P < 0.0001), but had a similar rate of primary percutaneous coronary intervention (14 vs. 15%; P = 0.2). Prior CABG patients were more likely to experience the composite outcome of cardiovascular death, MI, HF, resuscitated cardiac arrest, or stroke; 3 year Kaplan-Meier rate, 64 vs. 39% (adjusted hazard ratio 1.29, 95% confidence interval 1.17-1.43; P < 0.0001). Patients with prior CABG had a worse clinical profile and experienced more fatal and non-fatal outcomes. Greater recognition is necessary for these high-risk patients including optimization of evidence-based secondary preventive therapy.
    European Heart Journal 04/2009; 30(12):1450-6. · 14.72 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease is an independent predictor of mortality in patients with myocardial infarction (MI). However, the impact on mode of death and risk of atherosclerotic events is unknown. We assessed the risk of death and major cardiovascular (CV) events associated with chronic obstructive pulmonary disease in 14 703 patients with acute MI enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) trial. Cox proportional hazards models were used to evaluate the relationship between chronic obstructive pulmonary disease and CV outcomes. A total of 1258 (8.6%) patients had chronic obstructive pulmonary disease. Over a median follow-up period of 24.7 months, all-cause mortality was 30% in patients with chronic obstructive pulmonary disease, compared with 19% in those without. The adjusted hazard ratio (HR) for mortality was 1.14 (95% confidence interval 1.02-1.28). This reflected increased incidence of both non-CV death [HR 1.86 (1.43-2.42)] and sudden death [HR 1.26 (1.03-1.53)]. The unadjusted risk of all pre-specified CV outcomes was increased. However, after multivariate adjustment, chronic obstructive pulmonary disease was not an independent predictor of atherosclerotic events [MI or stroke: HR 0.98 (0.77-1.23)]. Mortality was significantly lower in patients receiving beta-blockers, irrespective of airway disease. In high-risk patients with acute MI, chronic obstructive pulmonary disease is associated with increased mortality and non-fatal clinical events (both CV and non-CV). However, patients with chronic obstructive pulmonary disease did not experience a higher rate of atherosclerotic events.
    European Journal of Heart Failure 02/2009; 11(3):292-8. · 5.25 Impact Factor
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    ABSTRACT: The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated. We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long-term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P<0.0001) and all-cause mortality (HR 1.19 per 1 SD increase, P<0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi-square). Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.
    European Journal of Heart Failure 02/2009; 11(2):170-7. · 5.25 Impact Factor
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    ABSTRACT: The purpose of this study was to identify predictors of incident diabetes during follow-up of nondiabetic patients with chronic heart failure (CHF) in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program. A total of 1,620 nondiabetic patients had full baseline datasets. We compared baseline demographic, medication, and laboratory data for patients who did or did not develop diabetes and conducted logistic regression and receiver operator characteristic curve analyses. Over a median period of 2.8 years, 126 of the 1,620 patients (7.8%) developed diabetes. In multiple logistic regression analysis, the following baseline characteristics were independently associated with incident diabetes in decreasing order of significance by stepwise selection: higher A1C (odds ratio [OR] 1.78 per 1 SD increase; P < 0.0001), higher BMI (OR 1.64 per 1 SD increase; P < 0.0001), lipid-lowering therapy (OR 2.05; P = 0.0005), lower serum creatinine concentration (OR 0.68 per 1 SD increase; P = 0.0018), diuretic therapy (OR 4.81; P = 0.003), digoxin therapy (OR 1.65; P = 0.022), higher serum alanine aminotransferase concentration (OR 1.15 per 1 SD increase; P = 0.027), and lower age (OR 0.81 per 1 SD increase; P = 0.048). Using receiver operating characteristic curve analysis, A1C and BMI yielded areas under the curve of 0.723 and 0.712, respectively, increasing to 0.788 when combined. Addition of other variables independently associated with diabetes risk minimally improved prediction of diabetes. In nondiabetic patients with CHF in CHARM, A1C and BMI were the strongest predictors of the development of diabetes. Other minor predictors in part reflected CHF severity or drug-associated diabetes risk. Identifying patients with CHF at risk of diabetes through simple criteria appears possible and could enable targeted preventative measures.
    Diabetes care 02/2009; 32(5):915-20. · 7.74 Impact Factor
  • Marc A Pfeffer
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    ABSTRACT: Epidemiologic observations showing associations between higher levels of some biologic markers such as blood pressure and serum cholesterol with heightened risk of death and non-fatal cardiovascular events have provided important data to develop hypotheses regarding pharmacologic therapies to modify these markers to improve prognosis. Randomized controlled trials have shown that strategies to reduce blood pressure with a variety of antihypertensive agents and LDL cholesterol with statins do, indeed, result in important improvements in clinical outcomes. However, there are several instances where a hypothesis based on strong observational data has been rejected based on surprising counterintuitive evidence generated from randomized controlled clinical trials. Use of inotropic therapies for patients with reduced left ventricular ejection fraction heart failure, administration of class I antiarrhythmic agents to suppress ventricular arrhythmias in high-risk patients, and use of hormone replacement therapy for postmenopausal women have each shown that therapies presumed to be of benefit may actually be producing unfavorable clinical results. Use of erythropoietic stimulating agents (ESA) in chronic kidney disease patients with anemia is similarly based on strong observational data indicating that the degree of anemia is independently associated with higher risk for cardiovascular morbidity and mortality. In non-dialysis patients with mild to moderate anemia, current clinical outcome studies have only addressed arbitrary hemoglobin targets for ESA therapy and have shown that targeting the higher hemoglobin levels was not associated with the benefit and may even result in harm. This review will outline the importance of having a placebo-controlled trial in this patient population to better assess the risk benefit profile of this therapy.
    Heart Failure Reviews 01/2009; 13(4):425-30. · 4.45 Impact Factor
  • Marc A Pfeffer, Frank M Sacks
    Circulation 01/2009; 118(24):2491-4. · 15.20 Impact Factor
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    ABSTRACT: This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (<or=0.40) in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) program. Hypotension is a predictor of poor prognosis in heart failure, yet many treatments shown to reduce morbidity and mortality lower blood pressure. This paradox creates a dilemma for physicians and may explain why low BP is reported as a reason for under-use of these agents. The interaction between treatment and baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) was examined with patients divided into 6 SBP categories (<or=100, 101 to 110, 111 to 120, 121 to 130, 131 to 140 and >or=141 mm Hg) and 4 DBP categories (<or=60, 61 to 70, 71 to 80 and >or=81 mm Hg). Low SBP and DBP were associated with worse clinical outcomes. Baseline BP did not modify the effects of candesartan on clinical outcomes: the interaction p value between SBP category and treatment was 0.38 (0.22 for DBP category). For both placebo and candesartan, study drug discontinuation for adverse effects (especially hypotension) was highest in patients in the lowest baseline BP categories. However, the relative risk of discontinuation for hypotension, renal dysfunction, and hyperkalemia in the candesartan compared with placebo group was not increased in patients with a low baseline BP. In patients with low EF heart failure, the relative risks and benefits of candesartan treatment were similar in patients with a low BP compared to those with a higher BP.
    Journal of the American College of Cardiology 01/2009; 52(24):2000-7. · 14.09 Impact Factor
  • Nephrology Dialysis Transplantation 01/2009; 2009(24):1663-1671. · 3.37 Impact Factor
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    ABSTRACT: We explored the impact of having a hospital admission for an acute coronary syndrome (ACS) on the subsequent prognosis among patients with chronic heart failure (CHF). A total of 7599 patients with CHF, New York Heart Association Classes II-IV, were randomly assigned to candesartan or placebo. We assessed the risk of death after a first ACS using time-updated Cox proportional hazard models adjusted for baseline predictors. During a mean follow-up of 3.3 years, 1174 patients experienced at least one ACS. Myocardial infarction (MI) was the first ACS in 442 subjects and unstable angina (UA) in 732. After these events, 219 (49.5%) and 167 (22.8%) patients died during follow-up. The early risk of death was more pronounced after MI: 30.2% died within 30 days compared with 3.6% after UA. After an ACS event, the risk of death declined steadily over time, although 18 months after an MI the risk was still twice that of patients without an ACS. Patients with CHF, who develop an ACS, have markedly increased subsequent mortality, particularly in the early phase after an MI.
    European Heart Journal 12/2008; 30(3):338-45. · 14.72 Impact Factor
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    ABSTRACT: To assess the relationship between left atrial (LA) size and outcome after high-risk myocardial infarction (MI) and to study dynamic changes in LA size during long-term follow-up. The VALIANT Echocardiography study prospectively enrolled 610 patients with left ventricular (LV) dysfunction, heart failure (HF), or both following MI. We assessed LA volume indexed to body surface area (LAVi) at baseline, 1 month, and 20 months after MI. Baseline LAVi was an independent predictor of all-cause death or HF hospitalization (P = 0.004). In patients who survived to 20 months, LAVi increased a mean of 3.00 +/- 7.08 mL/m(2) from baseline. Hypertension, lower estimated glomerular filtration rate, and LV mass were the only baseline independent predictors of LA remodelling. Changes in LA size were related to worsening in MR and increasing in LV volumes. LA enlargement during the first month was significantly greater in patients who subsequently died or were hospitalized for HF than in patients without events. Baseline LA size is an independent predictor of death or HF hospitalization following high-risk MI. Moreover, LA remodelling during the first month after infarction is associated with adverse outcome.
    European Heart Journal 12/2008; 30(1):56-65. · 14.72 Impact Factor
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    ABSTRACT: Hyperhomocysteinemia may be a modifiable risk factor for the prevention of arteriosclerotic outcomes in patients with chronic kidney disease (CKD). Few clinical trials of homocysteine lowering have been conducted in persons with CKD before reaching end-stage renal disease. Kidney transplant recipients are considered individuals with CKD. To describe the baseline characteristics of renal transplant recipients enrolled in a clinical trial of homocysteine lowering with a standard multivitamin containing high doses of folic acid and vitamins B(6) and B(12) aimed at reducing arteriosclerotic outcomes. Factors considered were level of kidney function, total homocysteine concentration, and prevalence of diabetes and previous cardiovascular disease (CVD). Cross-sectional survey within a randomized controlled trial cohort. Participants were recruited from kidney transplant clinics in the United States, Canada, and Brazil. Eligible participants had increased levels of homocysteine (> or =12.0 micromol/L in men and > or =11.0 micromol/L in women) and kidney function measured by means of Cockroft-Gault estimated creatinine clearance of 30 mL/min or greater. Of 4,110 randomly assigned participants, 38.9% had diabetes and 19.5% had previous CVD. Mean total homocysteine concentration was 17.1 +/- 6.3 (SD) micromol/L, whereas mean creatinine clearance was 66.4 +/- 23.2 mL/min. Approximately 90% of the trial cohort had an estimated glomerular filtration rate consistent with stages 2 to 3 CKD (i.e., 30 to 89 mL/min). Analysis is based on cross-sectional data from a randomized controlled trial, self-report of comorbid illnesses, and level of kidney function was estimated. A large population of stable renal transplant recipients who are at high risk of the development of CVD (both de novo and recurrent) has been recruited into the Folic Acid for Vascular Outcome Reduction in Transplantation Trial and are likely to experience a sufficient number of events to address the primary hypothesis of the trial.
    American Journal of Kidney Diseases 12/2008; 53(1):121-8. · 5.29 Impact Factor
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    ABSTRACT: Ageing may affect drug efficacy and safety in patients with heart failure (HF). The Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme offered an opportunity to study the relationship between increasing age and the efficacy and safety of treatment in an uniquely broad spectrum of patients with symptomatic HF and either reduced or preserved left ventricular ejection fraction. A total of 7599 patients in NYHA Class II-IV HF were randomized to candesartan (target dose 32 mg once daily, mean dose 24 mg) or placebo, including 3169 patients age >70 years. Mean follow-up was 37.7 months. The proportional hazards model was used to estimate the treatment effect on efficacy and safety within five age groups: <50 years (n = 605) (8% of all study patients), 50-59 years (n = 1474) (19%), 60-69 years (n = 2351) (31%), 70-79 years (n = 2474) (33%), and > or =80 years (n = 695) (9%). The risk of cardiovascular (CV) death or HF hospitalization (primary outcome) increased from 24% in the lowest age group to 46% in the highest age group (and mortality from 13 to 42%). The relative reduction in risk of the primary outcome with candesartan (15% in the overall study population) was similar irrespective of age. Consequently, the absolute benefit was greater with advancing age (3.8 patients avoided a primary outcome per 100 patients treated in the lowest age group compared with 6.8 in the highest). Adverse events leading to drug discontinuation were more frequent in the candesartan group: placebo/candesartan risk (%), lowest compared with highest age category: hyperkalemia (0.0/1.6 vs. 0.6/2.7), increased serum creatinine (1.0/3.9 vs. 6.1/5.4) and hypotension (1.7/2.0 vs. 2.8/5.7). Older patients were at a greater absolute risk of adverse CV mortality and morbidity outcomes but derived a similar relative risk reduction and, therefore, a greater absolute benefit from treatment with candesartan, despite receiving a somewhat lower mean daily dose of candesartan. Adverse effects were more common with candesartan than with placebo, although the relative risk of adverse effects was similar across age groups. The benefit to risk ratio for candesartan was thus favourable across all age groups.
    European Heart Journal 12/2008; 29(24):3022-8. · 14.72 Impact Factor
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    ABSTRACT: Recently, meta-analysis has been widely utilized to combine information across comparative clinical studies for evaluating drug efficacy or safety profile. When dealing with rather rare events, a substantial proportion of studies may not have any events of interest. Conventional methods either exclude such studies or add an arbitrary positive value to each cell of the corresponding 2 x 2 tables in the analysis. In this article, we present a simple, effective procedure to make valid inferences about the parameter of interest with all available data without artificial continuity corrections. We then use the procedure to analyze the data from 48 comparative trials involving rosiglitazone with respect to its possible cardiovascular toxicity.
    Biostatistics 11/2008; 10(2):275-81. · 2.43 Impact Factor
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    ABSTRACT: The curiosity that leanness is associated with poor survival in patients with chronic heart failure (CHF) needs further insight by investigating the impact of weight loss on prognosis in a large sample of patients across a broad spectrum of both reduced and preserved left ventricular (LV) systolic function. We investigated the change in weight over 6 months in 6933 patients in the Candesartan in Heart failure: Reduction in Mortality and morbidity (CHARM) programme, and its association with subsequent mortality (1435 deaths) over a median 32.9 months follow-up using Cox proportional hazard models to account for the impact of body mass index and other risk predictors. We then used time-updated Cox models to relate each patient's ongoing data on annual weight change to their mortality hazard. The percentage weight loss over 6 months had a highly significant monotonically increasing association with excess mortality, both for cardiovascular and for other causes of death. Patients with 5% or greater weight loss in 6 months had over a 50% increase in hazard compared with those with stable weight. Weight loss carried a particularly high risk in patients who were already lean at study entry. Findings were similar in the presence of dependent oedema, preserved or reduced LV ejection fraction, and treatment with candesartan, although weight loss was significantly less common on candesartan. The time-updated analyses revealed an even stronger link between weight loss and short-term risk of dying, i.e. risk increased more than four-fold for patients whose last recorded annual weight loss exceeded 10%. Weight gain had a more modestly increased short-term mortality risk. Weight loss accelerates in the year prior to death. Weight loss and leanness are important predictors of poor prognosis in CHF. Being lean and losing weight is particularly bad. The detection of weight change, and particularly weight loss, should be considered as an adverse sign prompting further evaluation.
    European Heart Journal 10/2008; 29(21):2641-50. · 14.72 Impact Factor
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    ABSTRACT: This study sought to understand prognostic implications of increased baseline left ventricular (LV) mass and geometric patterns in a high risk acute myocardial infarction. The LV hypertrophy and alterations in LV geometry are associated with an increased risk of adverse cardiovascular events. Quantitative echocardiographic analyses were performed at baseline in 603 patients from the VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study. The left ventricular mass index (LVMi) and relative wall thickness (RWT) were calculated. Patients were classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). Cox proportional hazards models were used to evaluate the relationships among LVMi, RWT, LV geometry, and clinical outcomes. Mean LVMi and RWT were 98.8 +/- 28.4 g/m(2) and 0.38 +/- 0.08. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, heart failure, stroke, or resuscitation after cardiac arrest was lowest for patients with normal geometry, and increased with concentric remodeling (hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.9 to 4.9), eccentric hypertrophy (HR: 3.1; 95% CI: 1.9 to 4.8), and concentric hypertrophy (HR: 5.4; 95% CI: 3.4 to 8.5), after adjusting for baseline covariates. Also, baseline LVMi and RWT were associated with increased mortality and nonfatal cardiovascular outcomes (HR: 1.22 per 10 g/m(2) increase in LVMi; 95% CI: 1.20 to 1.30; p < 0.001) (HR: 1.60 per 0.1-U increase in RWT; 95% CI: 1.30 to 1.90; p < 0.001). Increased risk associated with RWT was independent of LVMi. Increased baseline LV mass and abnormal LV geometry portend an increased risk for morbidity and mortality following high-risk myocardial infarction. Concentric LV hypertrophy carries the greatest risk of adverse cardiovascular events including death. Higher RWT was associated with an increased risk of cardiovascular complications after high-risk myocardial infarction.
    JACC. Cardiovascular imaging 10/2008; 1(5):582-91. · 14.29 Impact Factor
  • Article: In reply.
    Marc A Pfeffer
    American Journal of Kidney Diseases 09/2008; 52(3):627-8. · 5.29 Impact Factor
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    ABSTRACT: A progressive relationship between hemoglobin A(1c) (HbA(1c)) levels and cardiovascular (CV) events has been observed in persons with and without diabetes. To our knowledge, the nature of such a relationship in patients with symptomatic chronic heart failure (HF) has not been studied. A total of 2412 participants (907 with prior diabetes) in the Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program with at least 1 HbA(1c) level were followed up for a median of 34 months. The incidence of the primary outcome (CV death or HF hospitalization), CV death, and total mortality was calculated according to eighths of the usual HbA(1c) level ranging from 5.8% or less to greater than 8.6%. Adjusted and unadjusted hazard ratios per 1% rise in HbA(1c) levels were also calculated. A total of 99.6% of eligible participants were followed up until they developed an outcome or the study finished. The risk of the primary composite outcome, CV death, hospitalization for worsening HF, and total mortality rose progressively with higher levels of usual HbA(1c) (P for trend <.001). After age and sex were adjusted for, hazards of these outcomes per 1% higher HbA(1c) level were 1.25 (95% confidence interval [CI ], 1.20-1.31), 1.24 (95% CI, 1.17-1.31), 1.25 (95% CI, 1.19-1.31), and 1.22 (95% CI, 1.16-1.29), respectively. This relationship was evident in patients with and without diabetes and with reduced or preserved ejection fraction and persisted after adjustment for diabetes, other risk factors, and allocation to candesartan. In diabetic and nondiabetic patients with symptomatic chronic HF, the HbA(1c) level is an independent progressive risk factor for CV death, hospitalization for HF, and total mortality.
    Archives of internal medicine 08/2008; 168(15):1699-704. · 11.46 Impact Factor
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    ABSTRACT: To determine whether the risk of adverse cardiovascular (CV) outcomes associated with diabetes differs in patients with low and preserved ejection fraction (EF) heart failure (HF). We analysed outcomes in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme which randomized 7599 patients with symptomatic HF and a broad range of EF. The prevalence of diabetes was 28.3% in patients with preserved EF (>40%) and 28.5% in those with low EF (<or=40%). Diabetes was associated with a greater relative risk of CV death or HF hospitalization in patients with preserved EF [hazard ratio (HR) 2.0 (1.70-2.36)] than in patients with low EF [HR 1.60 (1.44-1.77); interaction test P = 0.0009]. For all-cause mortality, the risk conferred by diabetes was similar in both low and preserved EF groups. The effect of candesartan in reducing CV morbidity and mortality outcomes was not modified by having diabetes at baseline (P = 0.09 test for interaction). Diabetes was an independent predictor of CV morbidity and mortality in patients with HF, regardless of EF. The relative risk of CV death or HF hospitalization conferred by diabetes was significantly greater in patients with preserved when compared with those with low EF HF.
    European Heart Journal 07/2008; 29(11):1377-85. · 14.72 Impact Factor
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    ABSTRACT: African Americans have a high incidence of heart failure (HF). Limited retrospective observational subgroup analyses of patients with left ventricular systolic dysfunction (LVSD) suggest marginal benefit of angiotensin-converting enzyme inhibitors in the prevention of HF hospitalizations or total mortality in African Americans. Very few data exist concerning the effectiveness of angiotensin receptor blockers in this population. Baseline characteristics, treatments, and outcomes of patients from the U.S. (3,390 white and 340 African-American patients) in the VALIANT (VALsartan In Acute myocardial iNfarcTion) trial were compared. This trial included patients with an acute myocardial infarction (MI) after initial stabilization and documented LVSD and/or HF. Patients were randomly assigned to receive treatment with valsartan, captopril, or the combination; follow-up continued for up to 3 years (median 24.7 months). African Americans had more coronary risk factors, more markers of poor outcome after MI, and were less likely to be revascularized when compared with white patients. After adjusting for treatment assignment, baseline characteristics, and post-infarction parameters, no difference was found in the 3-year rate of all-cause mortality, cardiovascular mortality, rehospitalization for HF, recurrent MI, or stroke between the 2 groups. African Americans sustaining an acute MI with LVSD and/or HF had similar clinical outcomes compared with white Americans. Valsartan, captopril, or the combination had comparable effects on cardiovascular morbidity and mortality in African Americans and white Americans.
    Journal of the American College of Cardiology 06/2008; 51(19):1865-71. · 14.09 Impact Factor
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    ABSTRACT: In ACTIVE-W, oral anticoagulation (OAC) was more efficacious than combined clopidogrel plus aspirin (C+A) in preventing vascular events in patients with atrial fibrillation. However, because OAC carries important bleeding complications, risk stratification schemes have been devised to identify patients for whom the absolute benefits of OAC exceed its risks. Participants were risk-stratified with the widely-used CHADS(2) scheme. Treatment-specific rates of stroke and major bleeding were calculated for patients with a CHADS(2)=1 and compared to those with a CHADS(2)>1. Observed stroke rates for those with a CHADS(2)=1 were 1.25% per year on C+A and 0.43% per year on OAC (RR=2.96, 95% CI: 1.26 to 6.98, P=0.01). Among patients with a CHADS(2)>1, the stroke rates were 3.15% per year on C+A and 2.01% per year on OAC (RR=1.58, 95% CI: 1.11 to 2.24, P=0.01) (P for interaction between stroke risk category and efficacy of OAC=0.19). The risk of major bleeding during OAC was significantly lower among patients with CHADS(2)=1 (1.36% per year) compared with CHADS(2)>1 (2.75% per year) (RR=0.49, 95% CI 0.30 to 0.79, P=0.003). In this clinical trial, patients with a CHADS(2)=1 had a low risk of stroke, yet still derived a modest (<1% per year) but statistically significant absolute reduction in stroke with OAC and had low rates of major hemorrhage on OAC.
    Stroke 06/2008; 39(5):1482-6. · 6.16 Impact Factor

Publication Stats

44k Citations
5,941.92 Total Impact Points

Institutions

  • 1988–2014
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1982–2014
    • Brigham and Women's Hospital
      • • Division of Cardiovascular Medicine
      • • Center for Brain Mind Medicine
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2013
    • Golden Jubilee National Hospital
      Clydebank, Scotland, United Kingdom
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 2007–2013
    • Florida Atlantic University
      • Charles E. Schmidt College of Medicine
      Boca Raton, FL, United States
    • University of Oslo
      • Division of Medicine
      Kristiania (historical), Oslo County, Norway
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany
  • 2000–2013
    • Harvard University
      • • Department of Biostatistics
      • • Department of Nutrition
      Boston, MA, United States
  • 2012
    • Baker IDI Heart and Diabetes Institute
      Melbourne, Victoria, Australia
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2009–2012
    • IT University of Copenhagen
      København, Capital Region, Denmark
    • Akershus universitetssykehus
      Kristiania (historical), Oslo County, Norway
    • University of Colorado
      • Division of Cardiology
      Denver, CO, United States
  • 2011
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
    • Columbia University
      • Division of Cardiology
      New York City, NY, United States
  • 2007–2011
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2006–2011
    • London School of Hygiene and Tropical Medicine
      • Department of Medical Statistics
      London, ENG, United Kingdom
    • University of Groningen
      Groningen, Groningen, Netherlands
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden
    • University of Cape Town
      • Faculty of Health Sciences
      Cape Town, Province of the Western Cape, South Africa
  • 2005–2011
    • McMaster University
      • Population Health Research Institute (PHRI)
      Hamilton, Ontario, Canada
    • Auckland City Hospital
      Окленд, Auckland, New Zealand
  • 2002–2011
    • University of Glasgow
      • Institute of Cardiovascular and Medical Sciences
      Glasgow, Scotland, United Kingdom
    • Bristol-Myers Squibb
      New York City, New York, United States
  • 2010
    • Liverpool Heart And Chest Hospital
      Liverpool, England, United Kingdom
    • University of Copenhagen
      • Department of Cardiology
      Copenhagen, Capital Region, Denmark
    • University Center Rochester
      • Department of Medicine
      Rochester, Minnesota, United States
  • 1999–2010
    • University of Missouri
      Columbia, Missouri, United States
    • Dartmouth–Hitchcock Medical Center
      Lebanon, New Hampshire, United States
  • 2007–2009
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 1999–2009
    • Duke University
      Durham, North Carolina, United States
  • 2008
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Hamilton Health Sciences
      Hamilton, Ontario, Canada
    • University of Gothenburg
      Goeteborg, Västra Götaland, Sweden
    • University of Melbourne
      Melbourne, Victoria, Australia
  • 2005–2008
    • University of Alberta
      • • Division of Nephrology
      • • Department of Medicine
      Edmonton, Alberta, Canada
  • 1993–2008
    • Montreal Heart Institute
      • Department of Medicine
      Montréal, Quebec, Canada
  • 2000–2007
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
  • 2004–2006
    • University of Texas Southwestern Medical Center
      Dallas, Texas, United States
    • Medical University of Plovdiv
      • Division of cardiology
      Plovdiv, Oblast Plovdiv, Bulgaria
    • Monash University (Australia)
      • Cardiovascular Research Unit
      Melbourne, Victoria, Australia
  • 2003–2006
    • Duke University Medical Center
      • Division of Cardiology
      Durham, North Carolina, United States
  • 2001–2006
    • Baylor College of Medicine
      • Department of Medicine
      Houston, Texas, United States
    • Johannes Gutenberg-Universität Mainz
      • III. Department of Medicine
      Mainz, Rhineland-Palatinate, Germany
  • 1999–2004
    • University of Miami Miller School of Medicine
      • Division of Hospital Medicine
      Miami, FL, United States
  • 1995–2004
    • Mount Sinai Medical Center
      New York City, New York, United States
  • 1991–2004
    • University of Texas Health Science Center at Houston
      • • Division of Cardiovascular Medicine (Internal Medicine)
      • • School of Public Health
      Houston, TX, United States
    • Beth Israel Deaconess Medical Center
      • Department of Medicine
      Boston, MA, United States
  • 1998
    • San Francisco VA Medical Center
      San Francisco, California, United States
    • Geisinger Medical Center
      Danville, Pennsylvania, United States
  • 1995–1997
    • Vanderbilt University
      • • Department of Pharmacology
      • • Division of Pediatric Cardiology
      Nashville, MI, United States
    • University of Pennsylvania
      • Department of Medicine
      Philadelphia, PA, United States
  • 1984
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1975
    • University of Oklahoma Health Sciences Center
      Oklahoma City, Oklahoma, United States