Question of the Week #483

BACKGROUND:

Beta-blockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome.

METHODS:

In a multicenter, double blind, and randomized parallel group trial, we assigned 1511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II-IV), previous admission for a cardiovascular reason, an ejection fraction of less than 0.35, and to have been treated optimally with diuretics and angiotensin-converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality and the composite endpoint of all-cause mortality or all-cause admission. Analysis was done by intention to treat.

FINDINGS:

The mean study duration was 58 months (SD 6). The mean ejection fraction was 0.26 (0.07) and the mean age 62 years (11). The all-cause mortality was 34% (512 of 1511) for carvedilol and 40% (600 of 1518) for metoprolol (hazard ratio 0.83 [95% CI 0.74-0.93], p=0.0017). The reduction of all-cause mortality was consistent across predefined subgroups. Incidence of side effects and drug withdrawals did not differ by much between the two study groups.

 

  1. To which of the following patients are the results of this clinical trial applicable?
    1. A 62-year-old male with primarily diastolic congestive heart failure.
    2. A 75-year-old female with systolic dysfunction and an EF of 45%.
    3. A 56-year-old male with NYHA class I systolic heart failure.
    4. A newly diagnosed 66-year-old male who has yet to begin treatment for his NYHA class II systolic heart failure.
    5. A 68-year-old male with NYHA class II systolic heart failure and EF 30%.

 

Question of the Week #482

RESEARCH ABSTRACT QUESTION #1

BACKGROUND:

Aldosterone blockade reduces mortality and morbidity among patients with severe heart failure. We conducted a double blind, placebo-controlled study evaluating the effect of eplerenone, a selective aldosterone blocker, on morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.

METHODS:

Patients were randomly assigned to eplerenone (25 mg per day initially, titrated to a maximum of 50 mg per day; 3319 patients) or placebo (3313 patients) in addition to optimal medical therapy. The study continued until 1012 deaths occurred. The primary end points were death from any cause and death from cardiovascular causes or hospitalization for heart failure, acute myocardial infarction, stroke, or ventricular arrhythmia.

RESULTS:

During a mean follow-up of 16 months, there were 478 deaths in the eplerenone group and 554 deaths in the placebo group (relative risk, 0.85; 95 percent confidence interval, 0.75 to 0.96; P=0.008). Of these deaths, 407 in the eplerenone group and 483 in the placebo group were attributed to cardiovascular causes (relative risk, 0.83; 95 percent confidence interval, 0.72 to 0.94; P=0.005). The rate of the other primary end point, death from cardiovascular causes or hospitalization for cardiovascular events, was reduced by eplerenone (relative risk, 0.87; 95 percent confidence interval, 0.79 to 0.95; P=0.002), as was the secondary end point of death from any cause or any hospitalization (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.98; P=0.02). There was also a reduction in the rate of sudden death from cardiac causes (relative risk, 0.79; 95 percent confidence interval, 0.64 to 0.97; P=0.03). The rate of serious hyperkalemia was 5.5 percent in the eplerenone group and 3.9 percent in the placebo group (P=0.002), whereas the rate of hypokalemia was 8.4 percent in the eplerenone group and 13.1 percent in the placebo group (P<0.001).

  1. Which of the following statements represents the most accurate interpretation of the results from the aforementioned clinical trial?
    1. There was no significant difference in the incidence of hyperkalemia between trial arms.
    2. There was no significant difference in the rate of sudden cardiac death between trial arms.
    3. Epleranone, when added to optimal medical therapy, decreases all cause mortality in patients with left ventricular dysfunction following myocardial infarction.
    4. The rate of hypokalemia was not significantly different between trial arms.
    5. The most common causes of death seen in enrolled patients over the course of this trial were non-cardiac in nature.
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