Showing papers by "Marc A. Pfeffer published in 2006"

AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update Endorsed by the National Heart, Lung, and Blood Institute

Abstract: Since the 2001 update of the American Heart Association (AHA)/American College of Cardiology (ACC) consensus statement on secondary prevention,1 important evidence from clinical trials has emerged that further supports and broadens the merits of aggressive risk-reduction therapies for patients with established coronary and other atherosclerotic vascular disease, including peripheral arterial disease, atherosclerotic aortic disease, and carotid artery disease. This growing body of evidence confirms that aggressive comprehensive risk factor management improves survival, reduces recurrent events and the need for interventional procedures, and improves quality of life for these patients. Compelling evidence from recent clinical trials and revised practice guidelines provided the impetus for this update of the 2001 recommendations with evidence-based results (Table 1⇓). Classification of Recommendations and Level of Evidence are expressed in ACC/AHA format, as detailed in Tables 2 and 3⇓. Recommendations made herein are based largely on major practice guidelines from the National Institutes of Health and ACC/AHA. In many cases, these practice guidelines were supplemented by research findings published after the publication of the primary reference(s). Thus, the development of the present statement involved a process of partial adaptation of other guideline statements and reports and supplemental literature searches.2–32 (For specific search criteria, see the Appendix.) The findings from additional lipid reduction trials33–37 involving more than 50 000 patients resulted in new optional therapeutic targets, which were outlined in the 2004 update of the National Heart, Lung, and Blood Institute’s Adult Treatment Panel (ATP) III report.6 These changes defined optional lower target cholesterol levels for very high-risk coronary heart disease (CHD) patients, especially those with acute coronary syndromes, and expanded indications for drug treatment. …

Predictors of mortality and morbidity in patients with chronic heart failure

Abstract: Aims We aimed to develop prognostic models for patients with chronic heart failure (CHF). Methods and results We evaluated data from 7599 patients in the CHARM programme with CHF with and without left ventricular systolic dysfunction. Multi-variable Cox regression models were developed using baseline candidate variables to predict all-cause mortality ( n =1831 deaths) and the composite of cardiovascular (CV) death and heart failure (HF) hospitalization ( n =2460 patients with events). Final models included 21 predictor variables for CV death/HF hospitalization and for death. The three most powerful predictors were older age (beginning >60 years), diabetes, and lower left ventricular ejection fraction (EF) (beginning <45%). Other independent predictors that increased risk included higher NYHA class, cardiomegaly, prior HF hospitalization, male sex, lower body mass index, and lower diastolic blood pressure. The model accurately stratified actual 2-year mortality from 2.5 to 44% for the lowest to highest deciles of predicted risk. Conclusion In a large contemporary CHF population, including patients with preserved and decreased left ventricular systolic function, routine clinical variables can discriminate risk regardless of EF. Diabetes was found to be a surprisingly strong independent predictor. These models can stratify risk and help define how patient characteristics relate to clinical course.

Renal Function as a Predictor of Outcome in a Broad Spectrum of Patients With Heart Failure

Abstract: Background— Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. Methods and Results— The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (≤40%) or preserved LVEF (>40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 μmol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mo...

Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas

Abstract: Background—Cyclooxygenase-2 (COX-2) inhibitors have been shown to reduce colorectal adenomas but have been associated with increased cardiovascular risk. Methods and Results—The Adenoma Prevention With Celecoxib (APC) trial studied celecoxib 200 mg twice daily and 400 mg twice daily and the Prevention of Spontaneous Adenomatous Polyps (PreSAP) trial used 400 mg once daily to test the efficacy and safety of celecoxib against placebo in reducing colorectal adenoma recurrence after polypectomy. An independent safety committee for both studies adjudicated and categorized serious cardiovascular events and then combined individual patient data from these long-term trials to improve the estimate of the cardiovascular risk and blood pressure changes associated with celecoxib compared with placebo. For adjudicated cardiovascular events, 77% and 54% in APC and PreSAP, respectively, had 37 months of follow-up. For APC and PreSAP combined, 83 patients experienced cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure. The hazard ratio for this prespecified composite end point was 2.6 (95% confidence interval [CI], 1.1 to 6.1) in patients taking 200 mg twice daily, 3.4 (95% CI, 1.5 to 7.9) in patients taking 400 mg twice daily in APC, and 1.3 (95% CI, 0.6 to 2.6) in patients taking 400 mg once daily in PreSAP (P for heterogeneity0.13 comparing the combined doses in APC with the dose in PreSAP). The overall hazard ratio for this composite end point was 1.9 (95% CI, 1.1 to 3.1). Both dose groups in APC showed significant systolic blood pressure elevations at 1 and 3 years (200 mg twice daily: 1 year, 2.0 mm Hg; 3 years, 2.6 mm Hg; 400 mg twice daily: 1 year, 2.9 mm Hg; 3 years, 5.2 mm Hg); however, the 400 mg once daily group in PreSAP did not (P0.0001 between studies). Conclusions—Celecoxib at 200 or 400 mg twice daily or 400 mg once daily showed a nearly 2-fold–increased cardiovascular risk. The trend for a dose-related increase in cardiovascular events and blood pressure raises the possibility that lower doses or other dose intervals may be associated with less cardiovascular risk. (Circulation. 2006;114:1028-1035.)

Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program.

Abstract: Background— We wished to determine the prevalence of, potential mechanistic associations of, and clinical outcomes related to anemia in patients with heart failure and a broad spectrum of left ventricular ejection fraction (LVEF). Methods and Results— In multivariable analyses, we examined the associations between hemoglobin and baseline characteristics, laboratory variables, and outcomes in 2653 patients randomized in the CHARM Program in the United States and Canada. Anemia was equally common in patients with preserved (27%) and reduced (25%) LVEF but was more common in black and older patients. Anemia was associated with ethnicity, diabetes, low body mass index, higher systolic and lower diastolic blood pressure, and recent heart failure hospitalization. More than 50% of anemic patients had a glomerular filtration rate <60 mL · min−1 · 1.73 m−2 compared with <30% of nonanemic patients. Despite an inverse relationship between hemoglobin and LVEF, anemia was associated with an increased risk of death and...

Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial.

Abstract: Objectives To determine whether data on proteinuria are useful for refining estimates of risk based on kidney function alone, and whether the results of kidney function tests can be a useful adjunct to data on proteinuria. Design Analysis of data from a randomised trial. Impaired kidney function was defined as low glomerular filtration rate ( Setting Study of cholesterol and recurrent events: a randomised trial of pravastatin 40 mg daily versus placebo. Participants 4098 men and women with previous myocardial infarction. Main outcome measures All cause mortality and cardiovascular events. Results 371 participants died in nearly 60 months of follow-up. Compared with participants without proteinuria or impaired kidney function, patients with both characteristics were at high risk (hazard ratio 2.39, 95% confidence interval 1.72 to 3.30), and those with only proteinuria or only impaired kidney function were at intermediate risk (1.69, 1.32 to 2.16; 1.41, 1.12 to 1.79, respectively) of dying from any cause. The results were similar for cardiovascular outcomes, including new cases of heart failure, stroke, and coronary death or non-fatal myocardial infarction. A graded increase in the risk of all cause mortality was seen for severity of renal impairment and degree of proteinuria by dipstick. Conclusions The presence or absence of proteinuria on dipstick urinalysis may be used to refine estimates of risk based on kidney function alone.

Increase in Creatinine and Cardiovascular Risk in Patients with Systolic Dysfunction after Myocardial Infarction

Abstract: Baseline renal function is a potent independent risk factor for adverse events after acute myocardial infarction (MI). Worsening renal function (WRF) has been shown to influence outcomes in the heart failure population, but its impact on cardiovascular risk in the post-MI period has not been well defined. For assessment of the prognostic importance of WRF, 2231 patients who had left ventricular dysfunction and were enrolled in the Survival and Ventricular Enlargement (SAVE) trial were studied. Patients were randomly assigned between 3 and 16 d (average 11 d) after acute MI to receive captopril or placebo; those with a serum creatinine of >2.5 mg/dl were excluded from SAVE. WRF was defined as an increase in creatinine of >0.3 mg/dl measured from baseline to 2 wk after randomization. The predictive value of WRF on cardiovascular morbidity and mortality was examined during 42 mo of follow-up. Paired serum creatinine measurements at baseline and 2 wk were available in 1854 patients. WRF occurred in 223 (12.0%) patients and was a stronger predictor of death (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.05 to 2.02) than baseline creatinine (HR 1.31; 95% CI 1.01 to 1.70). WRF also showed an increased risk for cardiovascular death (HR 1.62; 95% CI 1.14 to 2.30) and the composite end point (HR 1.32; 95% CI 1.03 to 1.70). When stratified by treatment, 104 (5.7%) and 116 (6.4%) patients with WRF in the placebo and captopril groups had no significant association between treatment group and WRF (P = 0.38). The risk for death associated with WRF was HR 1.63 (95% CI 1.05 to 2.52) in the placebo group compared with HR 1.33 (95% CI 0.81 to 2.21) in the captopril group (P = 0.49 for interaction). WRF as early as 2 wk after MI was not uncommon (12.0%) and was associated with increased mortality in patients without renal dysfunction at baseline. Patients who received captopril did not demonstrate more WRF than patients who received placebo. Monitoring serum creatinine in patients during the first few weeks after MI may help to identify those who are at highest risk and guide effective long-term therapeutic choices.

Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial.

Abstract: Background— Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post–myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function. Methods and Results— We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, ...

Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction.

Abstract: Aims To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). Methods The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and/or LVSD. AF was assessed at presentation and at randomization (median 4.9 days after symptom onset). Primary outcomes were risk of death and major CV events 3 years following acute MI. Results A total of 1812 with current AF (AF between presentation and randomization), 339 patients with prior AF (history of AF without current AF), and 12,509 without AF were enrolled. Patients with AF were older; had more prior HF, angina, and MI, and received beta-blockers and thrombolytics less often than those without AF. Three-year mortality estimates were 20% in those without AF, 37% with current AF, and 38% with prior AF. Compared with patients without AF, the multivariable adjusted HR of death was 1.25 (1.03–1.52; p = 0.03) for prior AF and 1.32 (1.20–1.45; p < 0.0001) for current AF. HR for major CV events was 1.15 (0.98–1.35; p = 0.08) and 1.21 (1.12–1.31; p < 0.0001). Conclusion AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD.

The Charisma of Subgroups and the Subgroups of CHARISMA

Abstract: Antiplatelet therapy with aspirin, an irreversible inhibitor of platelet cyclooxygenase, has earned its rightful place as a cornerstone of treatment for reducing cardiovascular events in patients w...

Improvements in clinical outcomes with the use of angiotensin-converting enzyme inhibitors: cross-fertilization between clinical and basic investigation.

Abstract: The expanding clinical indications for the use of angiotensin-converting enzyme (ACE) inhibitors during the past three decades to reduce cardiovascular morbidity and mortality across a broad spectr

Comparison of regional versus global assessment of left ventricular function in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction: the valsartan in acute myocardial infarction echocardiographic study.

Abstract: Background Left ventricular (LV) ejection fraction (EF) and wall-motion index (WMI) have both been shown to be independent predictors of outcome after myocardial infarction (MI). Objectives We sought to determine whether these two measurements of LV systolic function provide similar or complementary information about prognosis after MI. Methods Echocardiography was performed in 610 patients with LV dysfunction, heart failure, or both after MI enrolled in the Valsartan in Acute MI trial. LVEF was estimated by biplane Simpson's rule, and WMI was assessed using a 16-segment model in 502 patients with echocardiograms of sufficient quality for wall-motion assessment. Results Both LVEF and WMI were independent predictors of adverse outcome after MI. LVEF conferred no additional prognostic information in multivariable analysis including WMI ( P = .39) or number of affected segments ( P = .53), whereas WMI ( P = .02) and total number of affected segments ( P = .006) remained significant even when adjusting for LVEF. Conclusions Assessment of regional dysfunction by WMI or the number of affected segments has slightly more prognostic value than LVEF in patients with LV dysfunction, heart failure, or both after MI. Regional assessment might be a more sensitive predictor of outcome than global assessment in patients with acute MI.

Rickettsia spp. in Ixodes ricinus Ticks in Bavaria, Germany

Abstract: This study aims to provide information on the occurrence of spotted fever rickettsiae in Ixodes ricinus ticks in southern Germany. A total of 2,141 I. ricinus ticks was collected in Bavaria. Pools of 5-10 ticks were studied by a PCR targeting the rickettsial citrate synthase gene gltA. The average prevalence rate was 12% (257 of 2,141). Sequencing data exclusively identified Rickettsia helvetica DNA. Results and other data demonstrate the possible role of R. helvetica in I. ricinus as a source of human infections in southern Germany.

Variable Impact of Combining Fatal and Nonfatal End Points in Heart Failure Trials

Abstract: Randomized clinical trials (RCTs) are a cornerstone of evidence-based medicine. Their design, implementation, and interpretation are sometimes subject to flaws and errors. To achieve statistical significance and economically feasible RCTs, the use of composite end points in heart failure (HF) trials has become more common. We analyzed the incremental value of combining HF hospitalizations with all-cause mortality in trials of chronic HF that enrolled >1000 placebo patients and had a mean follow-up >9 months. We tested the assumption that, compared with mortality, combining HF hospitalization with all-cause death would yield a consistently predictable increase in event rate across HF RCTs. Average placebo arm duration of follow-up was determined, and standardized placebo event rates per 100 patient-years were estimated. Twelve major HF RCTs were included in this analysis. There was a substantial relative increase in the event rate ranging from 64% to 134% when a composite end point was used. This increase was not related to disease severity as described by annual mortality rate. The relative contribution of combining HF hospitalization with all-cause mortality was, however, influenced by the duration of the trial. Combining HF hospitalization with all-cause mortality increases the overall event rate in HF clinical trials; the relative increase varies widely and is unrelated to disease severity. Longer-duration trials have a more predictable increase in events than short RCTs. Trial duration must be considered when composite end points are used during the design and interpretation of HF RCTs.

Cases of chikungunya imported into Europe.

Abstract: Epidemics of chikungunya fever are currently occurring on several islands in the Indian Ocean: Reunion, Mayotte, Mauritius, and Seychelles

Effect of pravastatin on blood pressure in people with cardiovascular disease

Abstract: Experimental evidence and several small studies in humans suggest that HMG-CoA (3-hydroxy 3-methylglutaryl coenzyme A) reductase inhibitors (statins) reduce blood pressure, perhaps through effects on endothelial function or by reducing inflammation. We tested the hypothesis that pravastatin would reduce blood pressure at 3 months and the risk of developing new hypertension over a follow-up period of 5 years. This was a post hoc subgroup analysis of a randomized double-blind placebo-controlled trial of pravastatin 40 mg daily vs placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol or =140/90 in those without known hypertension at baseline). This analysis included 4126/4159 (99.2%) participants for whom blood pressure was measured at baseline and during at least one follow-up visit. Median duration of follow-up was 57.8 months. The unadjusted and adjusted change in MAP, SBP, DBP or pulse pressure from baseline was not significantly different for pravastatin or placebo recipients at 3, 6, 12 or 24 months after randomization, or at last follow-up. Pravastatin did not reduce the adjusted risk of incident systolic hypertension (odds ratio 0.99, 95% CI 0.80-1.23), or incident diastolic hypertension (odds ratio 0.97, 95% CI 0.73-1.27). In summary, pravastatin 40 mg daily did not reduce blood pressure in survivors of myocardial infarction without overt hypercholesterolaemia.

Serum Phosphate: A Novel Cardiovascular Risk Factor Even in Nonrenal Patients Relation between Serum Phosphate Level and Cardiovascular Event Rate in People with Coronary Disease. Circulation 112: 2627-2633, 2005

Abstract: It has been known for decades that hyperphosphatemia is a feature of ESRD that may cause secondary hyperparathyroidism and soft tissue calcification ([1][1]), including vascular calcification ([2][2]). The latter comprises mainly calcification of intimal plaques ([3][3]) and of the media ([4][4],[5

Effect of angiotensin-converting enzyme inhibition on functional class in patients with left ventricular systolic dysfunction--a meta-analysis

Abstract: Background: The effect of angiotensin converting enzyme (ACE) inhibitors on symptoms in patients with left ventricular systolic dysfunction (LVSD) is controversial. Aims: To perform a meta-analysis of studies evaluating effect of ACE inhibitors on New York Heart Association (NYHA) class in patients with LVSD. Methods: Individual data from 10389 patients in NYHA classes I–IV from four large long-term studies (2–4-year follow-up) and summary data from 2302 patients in NYHA classes II–IV from 16 short-term studies (3 months follow-up) were meta-analysed to assess changes in NYHA class. Results: The large long-term studies showed a significant improvement in the worst NYHA classes (classes II–IV compared to class I) in the ACE inhibitor arm versus placebo, odds ratio (OR)=0.875 (0.811–0.943) p=0.0005. This effect was only present in studies which included patients with chronic heart failure and was particularly pronounced on deterioration to the worst NYHA class IV, OR=0.66 (0.52–0.84) p=0.001. There was no effect in the studies which included patients after myocardial infarction. The short-term chronic heart failure studies showed a significant improvement in NYHA class; OR for improvement of at least one NYHA class was 2.11 (1.48–2.98, 95% CI) p<0.0001. Conclusion: ACE inhibition significantly improves symptomatic status measured as NYHA classification in patients with chronic heart failure.

Pulsatile hemodynamic effects of candesartan in patients with chronic heart failure: the CHARM Program.

Abstract: Background: Abnormal large artery function and increased pulsatile load are exacerbated by excess angiotensin-II acting through the AT1 receptor and contribute to the pathogenesis and progression of chronic heart failure (CHF). Aims: To evaluate effects of the AT1 receptor blocker candesartan (N=30) or placebo (N=34) on pulsatile hemodynamics in participants with CHF in the CHARM program. Methods and results: Noninvasive hemodynamics were assessed following 6 and 14 months of treatment and averaged. Using calibrated tonometry and aortic outflow Doppler, characteristic impedance was calculated as the ratio of the change in carotid pressure and aortic flow in early systole. Total arterial compliance was calculated by the diastolic area method. Brachial blood pressure, cardiac output and peripheral resistance did not differ between groups. Lower central pulse pressure in the candesartan group (57±20 vs. 67±17 mmHg, P=0.043) was accompanied by lower characteristic impedance (200±78 vs. 240±74 dyne s/cm5, P=0.039) and higher total arterial compliance (1.87±0.70 vs. 1.47±0.48 ml/mmHg, P=0.008). Similar favorable differences were seen when analyses were stratified for ejection fraction (≤0.40 vs. >0.40) and baseline angiotensin converting enzyme inhibitor use. Conclusions: Candesartan has a favorable effect on large artery function in patients with chronic heart failure.