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Biomedical subjects

Marc A Pfeffer

Publications and source records attributed to Marc A Pfeffer.

At least 19 recordsLinked to original sources
PubMed2026

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a ≥15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

Humans↗
PubMed2004

Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.

BACKGROUND: The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined. METHODS: As part of the Valsartan in Acute Myocardial Infarction Trial (VALIANT), we identified 14,527 patients with acute myocardial infarction complicated by clinical or radiologic signs of heart failure, left ventricular dysfunction, or both, and a documented serum creatinine measurement. Patients were randomly assigned to receive captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups. RESULTS: The distribution of estimated GFR was wide and normally shaped, with a mean (+/-SD) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area. The prevalence of coexisting risk factors, prior cardiovascular disease, and a Killip class of more than I was greatest among patients with a reduced estimated GFR (less than 45.0 ml per minute per 1.73 m2), and the use of aspirin, beta-blockers, statins, or coronary-revascularization procedures was lowest in this group. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, congestive heart failure, stroke, or resuscitation after cardiac arrest increased with declining estimated GFRs. Although the rate of renal events increased with declining estimated GFRs, the adverse outcomes were predominantly cardiovascular. Below 81.0 ml per minute per 1.73 m2, each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 (95 percent confidence interval, 1.08 to 1.12), which was independent of the treatment assignment. CONCLUSIONS: Even mild renal disease, as assessed by the estimated GFR, should be considered a major risk factor for cardiovascular complications after a myocardial infarction.

Aged↗
PubMed2004

Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute myocardial infarction: the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial.

BACKGROUND: A prior diagnosis of diabetes mellitus is associated with adverse outcomes after acute myocardial infarction (MI), but the risk associated with a new diagnosis of diabetes in this setting has not been well defined. METHODS AND RESULTS: We assessed the risk of death and major cardiovascular events associated with previously known and newly diagnosed diabetes by studying 14,703 patients with acute MI enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. Patients were grouped by diabetic status: previously known diabetes (insulin use or diagnosis of diabetes before MI, n=3400, 23%); newly diagnosed diabetes (use of diabetic therapy or diabetes diagnosed at randomization [median 4.9 d after infarction], but no known diabetes at presentation, n=580, 4%); or no diabetes (n=10,719). Patients with newly diagnosed diabetes were younger and had fewer comorbid conditions than did patients with previously known diabetes. At 1 year after enrollment, patients with previously known and newly diagnosed diabetes had similarly increased adjusted risks of mortality (hazard ratio [HR] 1.43; 95% confidence interval [CI], 1.29 to 1.59 and HR, 1.50; 95% CI, 1.21 to 1.85, respectively) and cardiovascular events (HR, 1.37; 95% CI, 1.27 to 1.48 and HR, 1.34; 95% CI, 1.14 to 1.56). CONCLUSIONS: Diabetes mellitus, whether newly diagnosed or previously known, is associated with poorer long-term outcomes after MI in high-risk patients. The poor prognosis of patients with newly diagnosed diabetes, despite having baseline characteristics similar to those of patients without diabetes, supports the idea that metabolic abnormalities contribute to their adverse outcomes.

Aged↗
PubMed2004

Effect of pravastatin on cardiovascular events in people with chronic kidney disease.

BACKGROUND: Limited data describe the cardiovascular benefit of HMG-CoA reductase inhibitors (statins) in people with moderate chronic kidney disease (CKD). The objective of this analysis was to determine whether pravastatin reduced the incidence of cardiovascular events in people with or at high risk for coronary disease and with concomitant moderate CKD. METHODS AND RESULTS: We analyzed data from the Pravastatin Pooling Project (PPP), a subject-level database combining results from 3 randomized trials of pravastatin (40 mg daily) versus placebo. Of 19 700 subjects, 4491 (22.8%) had moderate CKD, defined by an estimated glomerular filtration rate of 30 to 59.99 mL/min per 1.73 m2 body surface area. The primary outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Moderate CKD was independently associated with an increased risk of the primary outcome (adjusted HR 1.26, 95% CI 1.07 to 1.49) compared with those with normal renal function. Among the 4491 subjects with moderate CKD, pravastatin significantly reduced the incidence of the primary outcome (HR 0.77, 95% CI 0.68 to 0.86), similar to the effect of pravastatin on the primary outcome in subjects with normal kidney function (HR 0.78, 95% CI 0.65 to 0.94). Pravastatin also appeared to reduce the total mortality rate in those with moderate CKD (adjusted HR 0.86, 95% CI 0.74 to 1.00, P=0.045). CONCLUSIONS: Pravastatin reduces cardiovascular event rates in people with or at risk for coronary disease and concomitant moderate CKD, many of whom have serum creatinine levels within the normal range. Given the high risk associated with CKD, the absolute benefit that resulted from use of pravastatin was greater than in those with normal renal function.

Adult↗
PubMed2004

Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial.

CONTEXT: Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome (ACS) event affect clinical outcome. OBJECTIVE: To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS. DESIGN, SETTING, AND PARTICIPANTS: International, randomized, double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter (n = 2265) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin (n = 2232), who were enrolled in phase Z of the A to Z trial between December 29, 1999, and January 6, 2003. MAIN OUTCOME MEASURE: The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, readmission for ACS, and stroke. Follow-up was for at least 6 months and up to 24 months. RESULTS: Among the patients in the placebo plus simvastatin group, the median low-density lipoprotein (LDL) cholesterol level achieved while taking placebo was 122 mg/dL (3.16 mmol/L) at 1 month and was 77 mg/dL (1.99 mmol/L) at 8 months while taking 20 mg/d of simvastatin. Among the patients in the simvastatin only group, the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL (1.76 mmol/L) and was 63 mg/dL (1.63 mmol/L) at 8 months while taking 80 mg/d of simvastatin. A total of 343 patients (16.7%) in the placebo plus simvastatin group experienced the primary end point compared with 309 (14.4%) in the simvastatin only group (40 mg/80 mg) (hazard ratio [HR], 0.89; 95% confidence interval [CI] 0.76-1.04; P =.14). Cardiovascular death occurred in 109 (5.4%) and 83 (4.1%) patients in the 2 groups (HR, 0.75; 95% CI, 0.57-1.00; P =.05) but no differences were observed in other individual components of the primary end point. No difference was evident during the first 4 months between the groups for the primary end point (HR, 1.01; 95% CI, 0.83-1.25; P =.89), but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin only group (HR, 0.75; 95% CI, 0.60-0.95; P =.02). Myopathy (creatine kinase >10 times the upper limit of normal associated with muscle symptoms) occurred in 9 patients (0.4%) receiving simvastatin 80 mg/d, in no patients receiving lower doses of simvastatin, and in 1 patient receiving placebo (P =.02). CONCLUSIONS: The trial did not achieve the prespecified end point. However, among patients with ACS, the early initiation of an aggressive simvastatin regimen resulted in a favorable trend toward reduction of major cardiovascular events.

Aged↗
PubMed2004

Clinically unrecognized Q-wave myocardial infarction in patients with diabetes mellitus, systemic hypertension, and nephropathy.

During the Irbesartan Diabetic Nephropathy Trial, 1,387 participants with type 2 diabetes mellitus, hypertension, and nephropathy underwent serial electrocardiograms for the identification of Q-wave myocardial infarction (MI). During a mean follow-up of 2.5 years, 14 of 99 first nonfatal MIs in this group were clinically unrecognized, accounting for 14% of all first nonfatal MIs.

Adult↗
PubMed2004

Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial.

CONTEXT: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibitor tirofiban with unfractionated heparin independently have shown superior efficacy over unfractionated heparin alone in patients with non-ST-elevation acute coronary syndromes (ACS). It is not clear if combining enoxaparin with glycoprotein IIb/IIIa inhibitors is as safe or as effective as the current standard combination of unfractionated heparin with glycoprotein IIb/IIIa inhibitors. OBJECTIVE: To assess efficacy and safety of the combination of enoxaparin and tirofiban compared with unfractionated heparin and tirofiban in patients with non-ST-elevation ACS. DESIGN, SETTING, AND PARTICIPANTS: A prospective, international, open-label, randomized, noninferiority trial of 1 mg/kg of enoxaparin every 12 hours (n = 2026) compared with weight-adjusted intravenous unfractionated heparin (n = 1961) in patients with non-ST-elevation ACS receiving tirofiban and aspirin. Phase A of the A to Z trial was conducted between December 1999 and May 2002. MAIN OUTCOME MEASURES: Death, recurrent myocardial infarction, or refractory ischemia at 7 days in the intent-to-treat population with boundaries set for superiority and noninferiority. Safety based on measures of bleeding using the Thrombolysis in Myocardial Infarction (TIMI) classification system. RESULTS: A total of 169 (8.4%) of 2018 patients randomized to enoxaparin experienced death, myocardial infarction, or refractory ischemia at 7 days compared with 184 (9.4%) of 1952 patients randomized to unfractionated heparin (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.71-1.08). This met the prespecified criterion for noninferiority. All components of the composite primary and secondary end points favored enoxaparin except death, which occurred in only 1% of patients (23 for enoxaparin and 17 for unfractionated heparin). Rates for any TIMI grade bleeding were low (3.0% for enoxaparin and 2.2% for unfractionated heparin; P =.13). Using a worst-case approach that combined 2 independent bleeding evaluations, use of enoxaparin was associated with 1 additional TIMI major bleeding episode for each 200 patients treated. CONCLUSIONS: In patients receiving tirofiban and aspirin, enoxaparin is a suitable alternative to unfractionated heparin for treatment of non-ST-elevation ACS. The 12% relative and 1% absolute reductions in the primary end point in favor of enoxaparin met criterion for noninferiority and are consistent with prior trials performed without the use of glycoprotein IIb/IIIa inhibitors.

Aged↗
PubMed2004

Effect of antecedent systemic hypertension on subsequent left ventricular dilation after acute myocardial infarction (from the Survival and Ventricular Enlargement trial).

Whether antecedent systemic hypertension influences the risk of subsequent left ventricular (LV) dilation in patients after an acute myocardial infarction with LV systolic dysfunction is unclear. We assessed echocardiographic evidence of ventricular remodeling from baseline (mean +/- SD 11 +/- 3 days) to 2 years after an acute myocardial infarction in 122 hypertensive (defined as a history of treated hypertension, baseline systolic blood pressure > or =140 or baseline diastolic blood pressure > or =90 mm Hg) and 334 nonhypertensive patients in the Survival and Ventricular Enlargement echocardiographic substudy. Compared with nonhypertensives, baseline heart size, defined as the sum of the average short- and long-axis LV cavity areas, was similar (70.1 +/- 11.9 vs 68.8 +/- 11.2 cm(2), p = 0.33 at end-diastole; 50.1 +/- 11.3 vs 48.8 +/- 10.8 cm(2), p = 0.31 at end-systole), but short-axis LV myocardial area (24.7 +/- 4.3 vs 25.7 +/- 5.0 cm(2), p = 0.043) and wall thickness (1.15 +/- 0.16 vs 1.21 +/- 0.17 cm, p = 0.004) at end-diastole were greater among hypertensives. The myocardial infarct segment lengths were similar in the 2 groups (p = 0.22). Although LV cavity areas increased significantly in the 2 groups from baseline to 2 years (p < or =0.001), the increase was significantly greater in hypertensives than in nonhypertensives (+5.6 +/- 11.5 vs +2.2 +/- 10.7 cm(2), p = 0.005 at end-diastole; +6.23 +/- 12.75 vs +2.94 +/- 11.4 cm(2), p = 0.012 at end-systole). There was no concomitant difference in the change in LV myocardial area or LV wall thickness between the 2 groups (p >0.30). After adjusting for known confounders, antecedent hypertension was associated with a doubling of the risk of LV dilation (50.8% vs 37.7%, odds ratio 2.09, 95% confidence interval 1.27 to 3.45, p = 0.004). This association was not modified by diabetes mellitus, myocardial infarct segment length, or captopril use (all p values for interaction >0.10). We conclude that antecedent hypertension is associated with subsequent LV dilation in patients after acute myocardial infarction with LV systolic dysfunction.

Antihypertensive Agents↗
PubMed2004

Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction.

OBJECTIVES: We assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI). BACKGROUND: In contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF. METHODS: The Survival And Ventricular Enlargement (SAVE) trial randomized 2231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI. RESULTS: Nondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome. CONCLUSIONS: In patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor.

Alcohol Drinking↗
PubMed2004

Angina pectoris prior to myocardial infarction protects against subsequent left ventricular remodeling.

OBJECTIVES: To investigate the hypothesis that prior angina pectoris confers protection from remodeling occurring after myocardial infarction (MI), we analyzed echocardiograms from the Healing and Early Afterload Reducing Therapy (HEART) trial. BACKGROUND: Ischemia occurring before MI has been shown to reduce infarct size in experimental models and to improve outcomes in patients. The extent to which ischemia occurring before MI influences subsequent changes in ventricular size and function is unclear. METHODS: We studied 283 patients enrolled in the HEART trial who had echocardiograms at days 1 and 90 after MI. Left ventricular (LV) dilation from days 1 to 90 was used as a measure of LV remodeling. We explored the relationship between symptomatic angina occurring before infarction and subsequent LV remodeling. RESULTS: In patients who reported angina (n = 111) during the three months preceding MI, LV volume change was -0.73 +/- 2.6 ml over the 90-day post-MI period, compared with 6.8 +/- 2.6 ml for patients (n = 172) without angina (p = 0.017). In contrast, there were no differences in changes in ejection fraction based on prior angina. Maximal creatine kinase was significantly lower in patients with prior angina (2,119 +/- 1,729 vs. 2,701 +/- 2,088, p = 0.016). In a multivariate model, prior angina remained protective for ventricular remodeling after adjusting for age, gender, baseline ejection fraction, Killip class, baseline end-diastolic volume, and drug treatment group (p = 0.042). However, the protective effect of pre-infarction angina appeared to be attenuated in diabetic patients. CONCLUSIONS: Ischemic symptoms occurring before MI may protect against LV remodeling. These protective effects may be secondary to recruitment of collaterals or ischemic preconditioning of the myocardium, and they appear to be attenuated in diabetic patients.

Aged↗
PubMed2004

Intensive versus moderate lipid lowering with statins after acute coronary syndromes.

BACKGROUND: Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear. METHODS: We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24). RESULTS: The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan-Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen. CONCLUSIONS: Among patients who have recently had an acute coronary syndrome, an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.

Angina, Unstable↗
PubMed2004

Antecedent hypertension and the effect of captopril on the risk of adverse cardiovascular outcomes after acute myocardial infarction with left ventricular systolic dysfunction: Insights from the Survival and Ventricular Enlargement Trial.

BACKGROUND: Hypertension is a well-established risk factor for myocardial infarction (MI), but its prognostic importance in survivors of an acute MI is less clear. METHODS: We used Cox proportional hazards models to examine the risk of any major cardiovascular event (cardiovascular death, heart failure, recurrent MI, or stroke)-combined or individual components-and all-cause death and evaluate the efficacy of captopril in 906 patients with hypertension and 1325 patients without hypertension in the Survival and Ventricular Enlargement (SAVE) clinical trial. All patients had survived an acute MI with resultant left ventricular (LV) systolic dysfunction, but without overt heart failure, and were randomized within 3 to 16 days after the index MI to receive either captopril or placebo. The mean (+/- SD) follow-up period was 42 +/- 10 months. RESULTS: After adjustment for known risk factors, medication use at enrollment, and baseline systolic blood pressure, patients with hypertension had a significant increase in the risk of experiencing a combined cardiovascular event (47.7% vs 31.3%; hazard ratio [HR], 1.49; 95% CI, 1.28-1.74), cardiovascular death (23.4% vs 15.9%; HR, 1.40; 95% CI, 1.12-1.74), heart failure (27.7% vs 15.5%; HR, 1.64; 95% CI, 1.34-2.02), and all-cause death (27.4 vs 19.3%; HR, 1.25; 95% CI, 1.02-1.53), and a similar but statistically non-significant increase in the risk of non-fatal or fatal recurrent MI (17.4% vs 10.9%; HR, 1.27; 95% CI, 0.98-1.65), and non-fatal or fatal stroke (5.0% vs 3.6%; HR, 1.31; 95% CI, 0.81-2.09). Captopril resulted in similar benefits for both patients with and patients without hypertension. The number of combined cardiovascular events prevented for every 100 patients treated with captopril was 7.0 (95% CI, 0.5-13.5) in patients with hypertension and 7.5 (95% CI, 2.6-12.5) in patients without hypertension. CONCLUSIONS: In survivors of an acute MI with LV systolic dysfunction, antecedent hypertension was associated with a greater risk of subsequent adverse cardiovascular events, not directly explained by elevated blood pressure levels. Captopril use was beneficial in both patients with and patients without hypertension.

Adult↗
PubMed2004

Cardiac remodeling in systemic hypertension.

Experimental and clinical studies provide evidence that hypertension is causally related to adverse cardiac structural changes, such as LA enlargement, LV hypertrophy and myocardial fibrosis, and functional changes inclusive of LV systolic and diastolic dysfunction. These changes are induced by both hemodynamic and nonhemodynamic factors. There is accumulating evidence from several small and large clinical trials that various classes of antihypertensive therapy prevent and regress LVH and myocardial fibrosis. Prevention and reversal of LVH are associated with an improvement in cardiac function and with a decline in risk of adverse cardiovascular outcomes. Prevention of LVH should be a priority in subjects with hypertension. In patients with hypertensive heart disease, the components of therapy must comprise optimization of BP and regression of LVH. Future targets of therapy in hypertensive heart disease may include regression of myocardial fibrosis, normalization of LA size, and improvement in LV diastolic function.

Animals↗
PubMed2003

Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients. METHODS: Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. RESULTS: During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartan-and-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. CONCLUSIONS: Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival.

Aged↗
PubMed2003

Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study.

OBJECTIVES: We sought to determine the predictors of heart failure (HF) development in long-term survivors of myocardial infarction (MI). BACKGROUND: Modern strategies of acute MI care have resulted in an increasing proportion of survivors at heightened risk of future non-fatal events, including HF. METHODS: We assessed the risk of developing HF in 3860 stable MI patients without a previous history of HF, who were enrolled in the Cholesterol And Recurrent Events (CARE) trial a median of 10 months post MI. Baseline characteristics of patients who did or did not develop HF during the five years of observation were assessed. RESULTS: A total of 243 patients (6.3%) developed HF in a linear pattern at a rate of 1.3%/year. Heart failure development markedly increased the risk of death (hazard ratio 10.2, 95% confidence interval 7.7 to 13.5). Fifty-seven patients (23.5%) who developed HF had a recurrent MI between enrollment and the onset of HF, increasing the risk fivefold. The most important predictors of HF were age and left ventricular ejection fraction. Other predictors included diabetes, history of hypertension, previous MI, and baseline heart rate. Moderate exercise three or more times per week was independently associated with a 30% lower risk of HF. CONCLUSIONS: Heart failure post MI occurs in a time-dependent fashion, which is usually not a direct consequence of a detectable interim MI. Patients who experience late-onset HF have a 10-fold increased risk of death compared with other MI survivors. Baseline characteristics can risk stratify patients at high risk of subsequent HF.

Age Factors↗
PubMed2003

Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial.

CONTEXT: Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis. OBJECTIVE: To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001. INTERVENTION: The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868). MAIN OUTCOME MEASURES: The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued. RESULTS: After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, -5% to 17%], P =.23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo. CONCLUSION: Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.

Anti-Bacterial Agents↗