Race and Ethnicity in Trials of Antihypertensive Therapy to Prevent Cardiovascular Outcomes: A Systematic Review

Ina U. Park; Anne L. Taylor

doi:10.1370/afm.708

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Response to: Race and ethnicity in trials of antihypertensive therapy to prevent cardiovascular outcomes: A systematic review. Ina U Park, MD and Anne L. Taylor, MD.
Cynthia M Ripsin

Published on: 24 October 2007
All We Know Is What We Know
Keith C. Ferdinand

Published on: 30 September 2007

Published on: (24 October 2007)
Page navigation anchor for Response to: Race and ethnicity in trials of antihypertensive therapy to prevent cardiovascular outcomes: A systematic review. Ina U Park, MD and Anne L. Taylor, MD.
Response to: Race and ethnicity in trials of antihypertensive therapy to prevent cardiovascular outcomes: A systematic review. Ina U Park, MD and Anne L. Taylor, MD.
Cynthia M Ripsin, Galveston, Texas
In their thorough review, Park and Taylor confirm once again our inadequacy to definitively answer questions of treatment efficacy based upon race. Present efforts to recruit racial minorities need improvement so the excessive burden of cardiovascular disease in these subgroups can be reduced.
A vexing question raised again by this review is the role of ACE inhibitors in treating hypertension in blacks. The...
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In their thorough review, Park and Taylor confirm once again our inadequacy to definitively answer questions of treatment efficacy based upon race. Present efforts to recruit racial minorities need improvement so the excessive burden of cardiovascular disease in these subgroups can be reduced.
A vexing question raised again by this review is the role of ACE inhibitors in treating hypertension in blacks. The notion that they are ineffective was propelled forward by the United States Veterans Affairs Cooperative study published in 1993 that concluded ACE inhibitors are less effective for lowering blood pressure in black than white subjects, and helped lead to the under-utilization of ACE inhibitors in black patients (1). However, the drop-out rate was 59% so the final analyses included fewer than 50 subjects each in younger and older black subgroups on ACE inhibitors. Park and Taylor have thoroughly summarized and discussed current studies on this topic but the question remains unanswered. Treatment decisions still need to be made even in the face of uncertainty, however, and that is where the JNC VII Guidelines are helpful(2). Contrary to Park and Taylor’s statement that ACE inhibitors are not recommended as first-line therapy for blacks, treatment strategies in the guidelines are not based upon race. Although there is discussion in the text regarding race, the algorithm for the initial treatment of hypertension begins with a thiazide-type diuretic for all patients and lists ACE inhibitors, angiotensin receptor blockers, calcium channel blockers and beta blockers as other first-line considerations if diuretics are contraindicated or if other compelling indications are present (i.e. Heart failure, post-MI, diabetes, high risk for CVD, kidney disease, recurrent stroke). ACE inhibitors are a first-line consideration in every compelling indication listed. Most patients will require a second agent for blood pressure control even in the early stages and blacks are at higher risk of essentially all of the compelling indications, so an ACE inhibitor is often the agent of choice to add along with a thiazide diuretic even for initial management.
The chasm that exists between fully understanding the ramifications of the care we deliver and the need to deliver care in the face of unanswered questions grows smaller when analyses like the one conducted by Park and Taylor are published, but will always be with us to some extent. Successfully crossing that chasm for the benefit of our patients is one example of the art of medicine.
References 1. Barry J. Materson, Domenic J. Reda, William C. Cushman, 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.
2. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee.Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003 Dec; 42(6):1206-52.
Competing interests: None declared
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Competing Interests: None declared.
Published on: (30 September 2007)
Page navigation anchor for All We Know Is What We Know
All We Know Is What We Know
Keith C. Ferdinand, Atlanta, USA
“Race and Ethnicity in Trials of Antihypertensive Therapy to Prevent Cardiovascular Outcomes: A Systematic Review.”
The article by Park and Taylor make a significant contribution to the medical literature. As the US becomes an increasingly heterogeneous population, clinicians will be challenged to apply results from previous large randomized trials to patients of various races and ethnicities. By limiting the n...
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“Race and Ethnicity in Trials of Antihypertensive Therapy to Prevent Cardiovascular Outcomes: A Systematic Review.”
The article by Park and Taylor make a significant contribution to the medical literature. As the US becomes an increasingly heterogeneous population, clinicians will be challenged to apply results from previous large randomized trials to patients of various races and ethnicities. By limiting the number of randomized studies reviewed for this analysis, Park and Taylor have appropriately resisted the approach of including large numbers of dissimilar clinical studies and arriving at an unsubstantiated conclusion. Most clinicians and researchers recognize the serious limitations of racial and ethnic categories. Indeed when faced with compelling situations, appropriate blood pressure control and the utilization of evidence-based drug classes for co-morbid conditions such as heart failure, kidney disease, and coronary heart disease is more important than the patient’s race or ethnic status. It is encouraging that some of the major trials including ALLHAT, INVEST, and VALUE show similar primary outcomes for blacks and Hispanics vs. the general study cohort. Nevertheless, ALLHAT suggests some degree of cardiovascular benefit with diuretics in blacks. The LIFE trial actually raises more questions than it answers, since this was a post hoc analysis of an under- powered sample of 533 blacks in approximately 9000 subjects.
The data are less robust for Asians and there are almost no data for Native Americans. Nevertheless, it is comforting that those studies that did include Asians were beneficial with calcium channel blockers for preventing cardiovascular outcomes. For practicing clinicians, perhaps the best utilization of this systematic review is by considering the comments in the discussion section. Wisely, they note multiple potential confounders within groups and across studies with wide variation in baseline characteristics, which may affect or even explain blood pressure outcomes and control. For instance, African Americans have more obesity, salt sensitivity, decreased potassium intake, and possibly excess sodium intake. Furthermore, limited educational attainment and decreased socioeconomic status may not only affect patients in an ambulatory setting but may also impact how patients respond to medications such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers in clinical studies.
In science, “all we know is what we know” cardiovascular disease is the primary cause of death for all populations, majority and minority. In an increasingly diverse society clinicians will need more evidence based studies to confidentially apply pharmacologic therapy across subpopulations. Nevertheless, in the interim, clinicians must diagnose hypertension early, treat intensively, educate and motivate patients regarding lifestyle modification and assist with all patients in achieving and maintaining quality medical care.
1. Chobanian AV, Bakris GL, Black HR, et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252.
2. Wright JT, Jr., Dunn JK, Cutler JA, et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005;293(13):1595-1608.
3. Douglas JG, Bakris GL, Epstein M, et al; Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Management of high blood pressure in African Americans: consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003;163(5):525-41.
4. Lindholm LH, Ibsen H, Dahlof B, et al.; LIFE Study Group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):1004-1010.
5. Ferdinand, KC. “Cardiovascular Disease and African Americans: Why Determination of Race is Inadequate for Research and Practice”. J Natl Med Assoc. 2007 Jun;99(6):686-689
Competing interests: None declared
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Competing Interests: None declared.