CREOLE: Amlodipine with Either Perindopril or Hydrochlorothiazide Is Better Than Perindopril and Hydrochlorothiazide in Reducing Blood Pressure In Black Patients in Sub-Saharan Africa

A trial led by Dr. Dike Ojji published in the New England Journal of Medicine showed that in black patients in sub-Saharan Africa, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering blood pressure at 6 months.

With increased blood pressure being the single largest contributor to the global burden of disease, there is a need to adequately manage this chronic condition. Results from multiple studies have shown that patients would typically need at least 2 anti-hypertensive medications to adequately control their hypertension (HTN). Currently, data indicates that the use of diuretics or calcium-channel blockers is more effective as monotherapy than other drug classes in black patients. However, the choice of which two antihypertensive medications should be used in black patients is not known and differs across guidelines in the United States and Europe, reflecting a lack of sufficient data in this population.

In this randomized, single-blind, three-group trial conducted in sub-Saharan Africa, black patients with a systolic blood pressure of 150-179 mm Hg while not on medication or a systolic blood pressure of 140-159 mm Hg while on monotherapy were randomized in a 1:1:1 ratio to receive a daily regimen of 5mg of amlodipine plus 12.5mg of hydrochlorothiazide, 5mg of amlodipine and 4mg of perindopril, or 4mg of perindopril and 12.5mg of hydrochlorothiazide for 2 months. Doses were then doubled for 4 months. The primary endpoint assessed was the change in the 24-hour ambulatory systolic blood pressure from baseline and 6 months. Secondary endpoints included the change in ambulatory diastolic blood pressure.

A total of 728 patients were randomized to one of the three study groups (244 to amlodipine + hydrochlorothiazide, 243 to amlodipine plus perindopril, and 241 to perindopril plus hydrochlorothiazide). The mean age at baseline was 51 and 63% of were women. Of the patients randomized, 95.9% completed the trial. A total of 621 patients (85.3%) had ambulatory blood pressure monitoring done at baseline and at 6 months. The primary analysis included the 621 patients who had ambulatory blood pressure monitoring at the two-time points. At baseline, the mean ambulatory systolic blood pressure was highest in the group that received amlodipine and perindopril (147.6±16.5 mm Hg, as compared to 145.6±14.6 mm Hg in the group that received amlodipine plus hydrochlorothiazide and 146.0±15.7 mm Hg in the group that received perindopril plus hydrochlorothiazide).

The investigators found that those receiving amlodipine plus hydrochlorothiazide and those receiving amlodipine plus perindopril had a lower 24 hour systolic BP measurement as compared to those receiving perindopril plus hydrochlorothiazide (between-group difference in change from baseline for amlodipine plus hydrochlorothiazide vs perindopril plus hydrochlorothiazide: −3.14 mm Hg; 95% CI −5.90 to −0.38, p=0.03; between-group difference in change from baseline for amlodipine plus perindopril vs perindopril plus hydrochlorothiazide: −3.00 mm Hg, 95% CI −5.8 to −0.20, p=0.04). However, there was no significant difference in the change in systolic BP in the group receiving amlodipine plus hydrochlorothiazide and the group receiving amlodipine plus perindopril (−0.14 mm Hg, 95% CI −2.90 to 2.61, p=0.92). However, there was no significant difference in the three treatment regimens with regards to ambulatory diastolic blood pressure (a secondary efficacy outcome) (Amlodipine plus hydrochlorothiazide versus perindopril plus hydrochlorothiazide: -1.05 mm Hg, 95% CI -2.67 to 0.55; amlodipine plus hydrochlorothiazide versus amlodipine plus perindopril: -0.41 mm Hg, 95% CI -2.01 to 1.18); amlodipine plus perindopril versus perindopril plus hydrochlorothiazide -0.64, 95% CI -2.27 to 0.98).

The investigators found that a two-drug combination of amlodipine with either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide in black patients in sub-Saharan Africa. The findings of this study suggest that amlodipine could be critical in adequately controlling blood pressure in this population. The findings here contrast with the current US recommendations that suggest using either a calcium channel blocker or diuretic with a different drug class. The findings also contrast with current European guidelines that recommend combining calcium channel blockers with either diuretics or ACE inhibitors or combining an ACE inhibitor with a diuretic. The findings of this trial address a serious knowledge gap and could potentially lead to a change in the current guidelines.