We systematically reviewed randomized controlled trials (RCTs) that consider the effect of initial dual antihypertensive combination treatment on blood pressure (BP), morbidity, or mortality in hypertensive African ancestry adults, using the methodology of the Cochrane Collaboration. Main outcomes were difference in means (continuous data) and risk ratio (dichotomous data).We retrieved 1728 reports yielding 13 RCTs of 4 weeks to 3 years duration (median 8 weeks) in 3843 patients. Systolic BP was significantly higher on β-adrenergic blocker vs. other combinations, 3.80 [0.82;6.78] mmHg, but comparable for other combinations. Hypokalemia and hyperglycemia occurred with calcium channel blocker (CCB) + diuretics > diuretics + angiotensin converting enzyme inhibitor (ACEI)/angiotensin-II-type-1-receptor antagonist (ARB) > CCB + ACEI/ARB. An RCT including high-risk patients reported combined morbidity/mortality for hydrochlorothiazide (mg) 25 + benazepril 40 vs. amlodipine 10 + benazepril 40 of respectively 8.9% vs. 6.6% (n = 1414, risk ratio 1.35 [0.94;1.94]; all patients, N = 11 506, 1.23 [1.11;1.37]).We conclude that limited evidence supports CCB + ACEI rather than HCT + ACEI as first-line initial combination therapy in African ancestry patients with hypertension.PROSPERO:CRD42021238529Graphical Abstract:http://links.lww.com/HJH/B835

Background Initial antihypertensive combination therapy is considered the standard of care in most patients with hypertension. However, while monotherapy with calcium channel blockers (CAB) or Diuretics is known to have greater blood pressure lowering efficacy than other drugs in African ancestry (AA) patients, it is unclear which initial combination therapy is most effective. Therefore, we systematically reviewed the existing evidence on different initial dual combination therapies in these patients. Methods We searched for published and unpublished randomized controlled trials (RCTs) in AA adults with uncomplicated, primary hypertension, which compared two or more initial dual combination drug therapies, and reported blood pressure, morbidity, or mortality outcomes. Searches were conducted without language restriction in electronic databases including PubMed, Embase, CENTRAL, preprint servers, and clinical trial registers, from their inception through March 31, 2021. In addition, we conducted hand search, and contacted authors and pharmaceutical companies for missing information. Trial quality was assessed using the Jadad score. Results We retrieved 1728 reports yielding 10 RCTs (Jadad score 1 to 4, median 3) conducted on 4 continents. Trials' treatment duration was 4 to 156 (median 10) weeks, using combinations of 6 classes of drugs in 23 treatment arms, and providing data on blood pressure (n=10 trials) and morbidity/mortality (n=1 trial) in 3715 patients (34.2% men) aged 18 to 79 years. Initial combination therapy with Diuretics+CAB (vs Diuretics+ACE-inhibitors (ACEI) or Angiotensin II type 1 receptor antagonists (ARB); 4 comparisons) resulted in comparable systolic (SBP) (n=467; −0.10 [−0.23 to −0.03] mm Hg), and diastolic blood pressure (DBP) (n=408; −0.03 [−0.19 to 0.12]). Adverse effects included more hypokalaemia and hyperglycaemia with Diuretics+CAB than Diuretic+ACEI/ARB. No morbidity or mortality outcomes were available. Initial combination therapy with CAB+ACEI/ARB (vs Diuretics+ACEI/ARB; 7 comparisons) also resulted in comparable blood pressures (n=2266; SBP: −0.49 [95% CI, −0.87 to −0.12] and DBP −0.55 [−0.97 to −0.14]); but CAB+ACEI/ARB showed less adverse effects (hypokalaemia, hyperglycaemia), and a trend toward reduced cardiovascular disease and mortality (n=1414; mean follow up 3 y; Amlodipine/Benazepril vs HCT/Benazepril, combined cardiovascular disease and mortality (6.6 vs 8.9%, P=0.10), without significant differences in Stroke (2.2 vs 2.1%, P=0.97), or heart failure (1.7 vs 2.2%, P=0.50). Conclusion In relatively young AA patients with uncomplicated hypertension, initial dual combination therapy including CAB, Diuretics, or Diuretics+CAB results in comparable blood pressures, but adverse metabolic effects are lower without a diuretic. Knowledge gaps include data on biomarkers to replace race/ancestry, data by sex and in the elderly, and end point data, including on Diuretic/CAB and CAB/ARB combinations. FUNDunding Acknowledgement Type of funding sources: None.