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Systematic Review: Antihypertensive Drug Therapy in Black Patients

Lizzy M. Brewster, MD; Gert A. van Montfrans, MD, PhD; and Jos Kleijnen, MD, PhD
[+] Article and Author Information

From Academic Medical Center, Amsterdam, the Netherlands, and University of York, York, United Kingdom.


Note: Some analyses included in this paper are reported in a Cochrane Collaboration systematic review, which is to be published in the Cochrane Library. Cochrane Collaboration reviews are updated regularly to take account of new data from randomized, controlled trials.

Acknowledgments: The authors thank the Dutch Cochrane Centre and the Cochrane Heart and Hypertension groups for their ongoing support during this review and all contacted authors and trial investigators for their willingness to supply supplemental trial data.

Potential Financial Conflicts of Interest:Grants received: G.A. van Montfrans (Pfizer, Yamanouchi, Solvay Pharmaceuticals, Menarini Group).

Corresponding Author: Lizzy M. Brewster, MD, Department of Internal Medicine, Academic Medical Center, F4-253, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands; e-mail, l.m.brewster@amc.uva.nl.

Current Author Addresses: Dr. Brewster: Department of Internal Medicine, Academic Medical Center, F4-222, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.

Dr. van Montfrans: Department of Internal Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.

Dr. Kleijnen: Centre for Reviews and Dissemination, University of York, York YO10 5DD, United Kingdom.


Ann Intern Med. 2004;141(8):614-627. doi:10.7326/0003-4819-141-8-200410190-00009
Text Size: A A A

Background: Hypertension occurs more frequently and is generally more severe in black persons than in white persons, leading to excess morbidity and mortality.

Purpose: To systematically review the efficacy of different antihypertensive drugs in reducing blood pressure, morbidity, and mortality in hypertensive black adults.

Data Sources: The following databases were searched from their inception through November 2003: MEDLINE, EMBASE, LILACS (Literatura Latino-Americana y del Caribe en Ciencias de la Salud), African Index Medicus, and the Cochrane Library. PubMed was also searched from September 2003 through March 2004. Searches were conducted without language restriction.

Study Selection: Randomized, controlled trials of drugs versus placebo (blood pressure outcomes) or drugs versus placebo or other drugs (morbidity and mortality outcomes).

Data Extraction: 2 reviewers independently extracted data.

Data Synthesis: The efficacy of β-blockers in reducing systolic blood pressure and the efficacy of angiotensin-converting enzyme inhibitors in achieving diastolic blood pressure goals did not significantly differ from that of placebo (weighted mean difference for β-blockers, −3.53 mm Hg [95% CI, −7.51 to 0.45 mm Hg]; relative risk for angiotensin-converting enzyme inhibitors, 1.35 [CI, 0.81 to 2.26]). In the pooled analyses, other reviewed drugs (calcium-channel blockers, diuretics, central sympatholytics, α-blockers, and angiotensin II receptor blockers) were more effective than placebo in reducing blood pressure, but only calcium-channel blockers remained effective in all prespecified subgroups, including patients with a baseline diastolic blood pressure of 110 mm Hg or greater. Main morbidity and mortality outcomes did not differ significantly between treatment groups when drugs were combined to reach blood pressure goals. However, trial results indicated a greater occurrence of diabetes with diuretics and a higher risk for cardiovascular events with drug regimens that included angiotensin-converting enzyme inhibitors.

Limitations: This meta-analysis evaluated the blood pressure lowering–efficacy of monotherapy only.

Conclusions: Drugs differ in their efficacy for reducing blood pressure in black patients, but there is no solid evidence that efficacy for reducing morbidity and mortality outcomes differs once patients achieve the blood pressure goal.

Figures

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Figure 1.
Trial flow.

With results for black patients in Materson and colleagues' study (6,30), the Systolic Hypertension in the Elderly Program (SHEP ) (49 ; unpublished report), the African American Study of Kidney Disease and Hypertension (56,57) , and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (60,61) contained in 2 reports. TAIM = Trial of Antihypertensive Interventions and Management; TOMHS = Treatment of Mild Hypertension Study.

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Figure 2.
Systolic blood pressure (SBP)–lowering effect of different antihypertensive drugs in black patients.

Random-effects model. Squares are weighted mean differences in reduction of SBP (mm Hg). The size of the squares represents study weight, and horizontal lines represent 95% CIs. Arrowheads depict data outside the scale. Results for Materson and colleagues' study (6)and Weir and colleagues' study (46) are weighted means of older and younger people and patients receiving a high- and a low-salt diet, respectively. Black diamonds are pooled estimates. Results for calcium-channel blockers are not pooled because the size of the effect is heterogeneous. ABC = Association of Black Cardiologists; TAIM = Trial of Antihypertensive Interventions and Management; TOMHS = Treatment of Mild Hypertension Study; TROPHY = Treatment in Obese Patients with Hypertension.

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Figure 3.
Diastolic blood pressure (DBP)–lowering effect of different antihypertensive drugs in black patients.

Random-effects model. Squares are weighted mean differences in reduction of DBP (mm Hg). The size of the squares represents study weight, and horizontal lines represent 95% CIs. Results for Materson and colleagues' study (6) and Weir and colleagues' study (46) are weighted means of older and younger people and patients receiving a high- and a low-salt diet, respectively. Black diamonds are pooled estimates. Results for calcium-channel blockers are not pooled because the size of the effect is heterogeneous. ABC = Association of Black Cardiologists; TAIM = Trial of Antihypertensive Interventions and Management; TOMHS = Treatment of Mild Hypertension Study; TROPHY = Treatment in Obese Patients with Hypertension.

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ACE inhibition in black patients
Posted on November 29, 2004
Jay S Kaufman
Department of Epidemiology, UNC School of Public Health
Conflict of Interest: None Declared

We read with interest the review article by Brewster and colleagues in which they summarized effects on blood pressure and blood pressure control of single antihypertensive agents reported in clinical studies that enrolled black patients in both the Americas and Africa. They highlight the observation that for ACE inhibitors the summary effect on diastolic control (as a binary outcome) did not differ significantly from placebo. However they also found that for these agents, changes in both systolic (-7.43 mmHg) and diastolic pressure (-3.35 mmHg) were each significantly greater than for placebo. The finding that the effect of ACE inhibition was non-significant in relation to placebo was based on only three studies, two of which enrolled participants with baseline DBP greater than or equal to 110 mmHg. Moreover, these two studies apparently used "per protocol analysis" (as opposed to intention-to-treat), and when only intention-to- treat analyses were considered the effect of ACE inhibition on DBP control was significantly greater than for placebo (RR = 1.74, 95% CI: 1.04, 2.92).

An additional concern is that participants on multiple antihypertensive medications with poorly controlled blood pressure were allowed in these trials and subsequently treated with a single drug regimen, a scenario that likely attenuated the in-trial response.

Blood pressure response distributions to ACE inhibitors overlap considerably between black and white populations. (1,2) That some antihypertensive therapies have reliably distinct effects in comparable black and white populations is an unlikely premise, and is also challenging because of the even greater social and genetic heterogeneity in black populations. For example, most of the genetic variability in the human species occurs within African-origin populations (3), and most genetic and social heterogeneity is within racial groups, not between them. The most sensible null hypothesis from which to work in any study of drug effects is that of homogeneity of effects across continental populations. When there is evidence of significant effect measure heterogeneity, then this null hypothesis may be rejected and the search for biological or social explanations may commence. However this present meta-analysis should not be over-interpreted as providing evidence for such differential treatment effects that merit differential prescribing patterns by race.

Jay S. Kaufman, Ph.D. John M. Flack, M.D., M.P.H

1. Mokwe E, Ohmit SE, Nasser SA, Shafi T, Saunders E, Crook E, Dudley A, Flack JM. Determinants of blood pressure response to quinapril in black and white hypertensive patients: the Quinapril Titration Interval Management Evaluation trial. Hypertension. 2004 Jun;43(6):1202-7.

2. Sehgal AR. Overlap between whites and blacks in response to antihypertensive drugs. Hypertension. 2004 Mar;43(3):566-72.

3. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D. The structure of haplotype blocks in the human genome. Science. 2002 Jun 21;296(5576):2225-9.

Conflict of Interest:

None declared

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