Initial combination therapy for hypertension in patients of African ancestry: a systematic review and meta-analysis

Abstract

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

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

“…BP associations with CV risk have also been broadly consistent across ethnic groupings [1051]. Based on systematic reviews [1052] in people of SSA ancestry, CCB and diuretic monotherapies appear to be more effective than BB and ACEi monotherapies, with combination therapy between major drug classes allowing a substantial group of patients (50-70%) to reach BP control [1052,1053]. This is similar to the results of the ALLHAT trial in the USA, which included 33% African Americans [566,1054] and found that BP control at 4 years was 63, 60 and 54% with chlorthalidone, amlodipine, and lisinopril-based therapy, respectively.…”

“…However, 24, 28 and 41% of patients of the corresponding groups received 3 drugs, including the BB atenolol. A recent systematic review and meta-analysis [1052] indicated that, in hypertensive adults of African ancestry, BP reduction was similar across initially administered dual combination therapy containing an RAS inhibitor with a CCB, or a diuretic while with a BB in combination therapy, SBP showed a 3.8 mmHg higher SBP compared with other combinations [1048,1052]. An RCT with African patients from seven SSA countries has also shown an effective BP reduction (ABPM) using a CCB in combination with either a Thiazide or an ACEi [1055].…”

Arterial Hypertension in Women: State of the Art and Knowledge Gaps

“…16,26,[68][69][70][71][72] Sex-neutral clinical practice guidelines [1][2][3] insufficiently acknowledge that clinical studies are often underpowered for women, such that "evidence creating" results could only be obtained for men or for both sexes together. Data particularly lack for specific subgroups, for example, pregnant women, women with gynecological disorders, women with a history of adverse pregnancy outcomes, women of color, and peri and postmenopausal women 16,26,[69][70][71] In addition, the higher cardiovascular risk with gynecological conditions and adverse pregnancy outcomes is absent from recommendations for history taking or currently used risk assessment tools, which tend to underestimate cardiovascular risk in women. [1][2][3]16,23,68 Moreover, women, especially women of color, less often receive the current, sex-neutral cardiovascular guideline-recommended care.…”

“…71 Metformin and RAS blockers have also been proposed for women with fibroids or a history of adverse pregnancy outcomes. 16,70,78 However, RAS blocker monotherapy might be less effective in women of African ancestry, 69 and these drugs are fetotoxic. [1][2][3] Finally, women tend to experience more adverse effects of antihypertensive drugs, probably due to understudied sex differences in pharmacokinetic or pharmacodynamic properties.…”

“…There is a general paucity of data on specific antihypertensive drug therapy over the lifespan of women, regarding treatment thresholds, treatment goals, choice of drugs, and efficacy and adverse events. 16,26,68–72 Sex-neutral clinical practice guidelines 1–3 insufficiently acknowledge that clinical studies are often underpowered for women, such that “evidence creating” results could only be obtained for men or for both sexes together. Data particularly lack for specific subgroups, for example, pregnant women, women with gynecological disorders, women with a history of adverse pregnancy outcomes, women of color, and peri and postmenopausal women 16,26,69–71 In addition, the higher cardiovascular risk with gynecological conditions and adverse pregnancy outcomes is absent from recommendations for history taking or currently used risk assessment tools, which tend to underestimate cardiovascular risk in women.…”