Calcium Antagonists in Blacks (CAB) Clinical Trial - Guest Editorial
A Perspective on the Calcium Antagonists in Blacks (CAB) Trial
W. Dallas Hall, MD, MACP
Emeritus Professor of Medicine
Emory University School of Medicine
Atlanta, Georgia
Calcium channel antagonists (CCAs) are very effective antihypertensive drugs when used in hypertensive blacks. This statement was borne out by the 10-center CAB trial where once-daily monotherapy with each of the three tested dihydropyridine CCAs produced excellent average reductions in the office visit blood pressure (BP) of 163 hypertensive blacks, ranging from 19/12 to 22/14 mm Hg. The eight-week decrease in BP (either at the office visit or by computerized 24-hour monitoring) did not differ significantly among the three drugs.
The adverse effect profile was also very similar among the three drugs. Particularly striking was the absence of pretibial or pedal edema (despite 67% women in the cohort) at the clinic visits, where edema was sought specifically by each investigative team. Although it is possible that dihydropyridine-induced edema is less common in blacks as compared to whites, it is more likely that edema was not detected because 1) the maximal daily doses were limited to 10 mg amlodipine or 60 mg nifedipine, 2) patients with edema at baseline were excluded, and 3) clinic visits occurred in the morning hours in order to obtain trough levels of BP. Edema was self-reported by 14.3%, 10.5% and 8.5% of patients receiving amlodipine besylate, nifedipine coat core (CC) or nifedipine gastrointestinal therapeutic system (GITS), respectively (P=NS).
The absolute reductions in BP were not placebo-corrected, but they were comparable to or greater than the 15/15 mm Hg reduction using monotherapy with 120-360 mg daily of a sustained-release preparation of diltiazem used in 90 black men in the Veterans Affairs Cooperative Study.1 We must not become complacent, however, about an excellent response to one particular class of antihypertensive drugs when only 55% of treated U.S. hypertensives are controlled. The proportions controlled are even worse in treated blacks: 47% of black men (vs 50% of white men) and 49% of black women (vs 60% of white women).2 For the majority of hypertensive blacks, two or more antihypertensive drugs will be necessary to control systolic BP to < 140 mm Hg and diastolic BP to less than 90 mm Hg. Data from the African American Study of Kidney Disease and Hypertension (AASK) pilot study indicated that an average of 2.5 drugs was required to attempt reduction of mean arterial BP to <92-107 mm Hg in hypertensive blacks with evidence of mild-to-moderate renal dysfunction.3
Cost was not assessed in the CAB trial, but has a recognized influence on compliance to antihypertensive therapy and control of blood pressure in blacks.4-6 Adalat CC costs substantially less than the other two drugs studied.
A major feature of the CAB trial was that it illustrated that a post-marketing Phase IV clinical trial can be as scientific as any pre-marketing Phase III study. CAB was a formally randomized, double-blind trial with a placebo lead-in period, pre-study investigator training, and rigorous criteria for measurement of BP, timing of visit windows, and other trial components. Data analysis was independent of both the investigators and the sponsor.
Another outstanding feature of the CAB trial was that it represented a joint clinical research collaboration between an industry sponsor and a nonprofit organization. Bayer Corporation funded the study and reviewed the results. They pre-agreed that the nonprofit organization could submit the results for publication regardless of the outcome. The International Society on Hypertension in Blacks, Inc. (ISHIB) was the nonprofit organization, with Kermit G. Payne as executive director and CAB project coordinator.
I and James W. Reed, MD served as the ISHIB CAB Project Co-Directors and were not investigators in the study. ISHIB and the Project Co-Directors wrote the protocol, selected 10 very experienced principal investigators (all ISHIB members) and study sites, designed and printed the case report forms, conducted the site monitoring visits, and selected the Data Analysis and Coordinating Center (Bowman Gray School of Medicine, John M. Flack, MD, MPH, Director).
The primary mission of ISHIB, to improve the quality of life and impact on morbidity and mortality among ethnic populations, blended well with the CAB study. Both ISHIB and the Bayer Corporation shared in this mission and should be congratulated on this important research contribution.
References
- Materson BJ, Reda DJ, Cushman WC, Massie BM, Fries ED, Kochar MS, et al, for the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. N Engl J Med. 1993; 328: 914-921.
- Burt VL, Cutler JA, Higgins M, Horan MJ, Labarthe D, Whelton P, et al. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population. Data from the Health Examination Surveys, 1960 to 1991. Hypertension. 1995; 26: 60-69.
- Lee JY, Greene PG, Douglas M, Grim C, Kirk KA, Kusek JW, et al, for the AASK Pilot Study Investigators. Appointment attendance, pill counts, and achievement of goal blood pressure in the African American Study of Kidney Disease and Hypertension Pilot Study. Control Clin Trials. 1996; 17 (4S): 34S - 39S.
- Shulman NB, Levinson RM, Dever GEA, Porter RS, Owen SL, Hall WD. Impact of cost problems on morbidity in a hypertensive population. Am J Prev Med. 1991; 7: 374-378.
- Ahluwalia JS, McNagny SE, Rask KJ. Correlates of controlled hypertension in indigent, inner-city hypertensive patients. J Gen Intern Med. 1997; 12: 7-14.
- Moser M. The cost of treating hypertension. Can we keep it under control without compromising the level of care? Am J Hypertens. 1998; 11 (8, Pt 2): 120S - 127S.
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