Race-based Therapy for Hypertension: Possible Benefits and Potential Pitfalls

Keith C. Ferdinand; Daphne P. Ferdinand


Expert Rev Cardiovasc Ther. 2008;10(6):1357-1366. 

In This Article

Race/Ethnicity in Cardiovascular Outcome Trials

This section is included after discussion of pathophysiology, clinical efficacy and safety trials due to the fact that cardiovascular outcome data are very limited, other than a few major trials which enrolled significant proportions of African-Americans and Hispanics.[36,37] The participation of various racial/ethnic groups, other than White/European populations, have been inconsistent and the data often inadequate or not measured. The ALLHAT trial, however, of 33,357 participants included subgroups consisting of 47% women, 35% Black, 19% Hispanic and 36% with diabetes. There were nearly identical distributions of baseline factors in the chlorthalidone, amlodipine and lisinopril treatment groups. This National Heart, Lung, and Blood Institute trial proactively enrolled a significant number of Blacks, considering the large burden of hypertension-related disease in this population.[44] Overall, the primary end point (fatal CHD and nonfatal myocardial infarction) was similar in Blacks versus the general study population. Blood pressure decreased in non-Blacks receiving lisinopril similarly to those receiving chlorthalidone. However, BP-reduction with lisinopril was significantly lower in Blacks compared with diuretic patients. At 2 years, Blacks demonstrated 5/2 mmHg greater BP reduction on average with chlorthalidone versus lisinopril, and 4/1 mmHg greater reduction at 4 years with chlorthalidone and amlodipine. Blood pressure was similar in Blacks and Whites (138/80 vs 140/80 mmHg).[44] However, in Blacks versus Whites, there was a 40% increase in the risk of stroke with lisinopril versus chlorthalidone, 1.4 (1.17-1.68). Amlodipine and chlorthalidone for Blacks had no significant difference in stroke. Perhaps much of the difference related to lisinopril and stroke may have been driven by a 4-5 mmHg higher systolic BP in the Black lisinopril-based group than in the chlorthalidone-based therapy. Furthermore, doxazosin, an α-1 blocking agent, produced less BP-lowering in Blacks and was withdrawn prematurely from ALLHAT because of evidence of less protection from CVD in the general cohort compared with chlorthalidone.[36]

The AASK included 1,094 self-identified African-Americans aged 18-70 years, with hypertension, and decreased glomerular filtration rates of 20-65 ml/min/1.73 m2.[42] Patients with hypertensive nephropathy were randomized to therapy based on ramipril, metoprolol succinate or amlodipine. In AASK, with patients with significant proteinuria, the rate of renal function decline was slowed with ramipril. Thus, African-Americans patients with hypertensive nephropathy, should have treatment with an ACEI, especially if proteinuria is present.[42] Despite improvement in renal function, patients demonstrated lower mean systolic and diastolic BP from baseline to 3 month follow-up, respectively, with amlodipine (150/96 to 133/81 mmHg) than with ramipril (151/96 to 135/82 mmHg).[42]

A systematic review was published by Park and Taylor in 2007 to determine racial and ethnic minorities in clinical antihypertensive trials of drug therapy and differences between groups in large outcomes antihypertensive trials.[59] The two authors independently assessed studies for inclusion and quality after searching major data bases via online review. A total of 28 trials met the criteria for inclusion, with eight that had CVD outcomes evidence. For Blacks and Hispanics, three trials (ALLHAT, INVEST and the Valsartan Long-term Use Evaluation) showed similar primary outcomes.[36,37,60,61,62] On the other hand, one trial, the Protection Against Recurrent Stroke Study, compared Asians with non-Asians and demonstrated that ACEIs versus placebo equally protected from stroke for White, with Asians having significantly greater BP reductions.[59] In addition, three studies with CCBs with Asian populations (Japanese Multicenter Investigation of Cardiac Disease, Felodipine Event Reduction Study and National Intervention Cooperative Study in Elderly Hypertensives) demonstrated effectiveness with CCBs for decreasing CVD.[63,64,65]


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