Race and the Response to Carvedilol
Source: Yancy CW, et al. N Engl J Med. 2001;344:1358-1365.
The best study showed a poor response to the beta-blocker bucindolol in black individuals.1 Also, the SOLVD studies showed lack of efficacy of the angiotensin-converting enzyme inhibitor enalapril in blacks with reduced left ventricular (LV) function, with or without overt heart failure.2 Thus, the report of Yancy and colleagues for the US Carvedilol Heart Failure Study Group is of interest. Of the 1094 patients with symptomatic heart failure and LV ejection fraction (EF) < 35% despite maximal therapy with conventional therapy, 217 (20%) were black. The end points of LVEF, clinical status, and major cardiac events were retrospectively compared in this randomized, placebo-controlled trial between the blacks and nonblacks. The combined end point of death or hospitalization for any reason was reduced 48% in blacks and 30% in nonblacks (P = NS) by carvedilol vs. placebo. Clinical progression of heart failure was also significantly reduced by carvedilol in both groups (relative risk [RR] in blacks 0.46 and 0.49 in nonblacks). LVEF increased in both groups on carvedilol (10% in blacks, 8% in nonblacks; P < 0.001 for both). During the 2-week open-label carvedilol therapy period, the number of blacks who discontinued therapy was similar to nonblacks (5% vs 7%, respectively) as was withdrawal for adverse events throughout the study. Yancy et al concluded that the response to carvedilol added to conventional therapy in patients with symptomatic heart failure due to systolic dysfunction is of similar magnitude in blacks and nonblacks.
Comment by Michael H. Crawford, MD
The results of this analysis of the Carvedilol Study Group pooled data is encouraging for the treatment of heart failure in blacks, since they are known to have a higher incidence of heart failure compared to nonblacks, and have more rapid progression of heart failure once diagnosed. The reason heart failure is more common in blacks may be due to their higher incidence of hypertension and diabetes, or environmental factors such as restricted access to health care. Thus, heart failure in blacks is a major public health problem.
The major criticism of this study is that it was not a prospective, randomized trial of response in different racial groups. In fact, the nonblack group included those of European, Asian, and Native American descent. So the results could be just due to vagaries of patient selection. However, the blacks in this study had similar characteristics to the blacks in other heart failure trials, namely a higher incidence of hypertension and less ischemic heart disease.
Why blacks did better on carvedilol than the results reported for bucindolol may be due to the alpha-blocking properties of carvedilol. Interestingly, labetolol, a combined alpha-beta-blocker, has been shown to be superior to propranolol in blacks with hypertension.3 Also, alpha blockade may improve insulin sensitivity and serum lipids in patients on a beta-blocker, which may be especially important in blacks with vascular disease. Whatever the mechanism, until further data are forthcoming, blacks with heart failure who are treated with beta-blockers should probably receive carvedilol.
References
1. BEST Investigators. N Engl J Med. 2001;344:1659-1667.
2. Exner DV, et al. N Engl J Med. 2001;344:1351-1357.
3. Flammenbaum W, et al. J Clin Hypertens. 1985;1:56-69.
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