Trial Pinpoints Effective BP Combos for Black Africans

NEW ORLEANS — Black sub-Saharan African patients with hypertension appeared to benefit from combining amlodipine with either perindopril or hydrochlorothiazide (HCTZ), a researcher said here.

Among the participants in the randomized CREOLE trial, mean blood pressure reductions at 6 months were 3.00 mm Hg greater (P=0.04) with perindopril plus amlodipine, and 3.14 mm Hg greater (P=0.03) with HCTZ plus amlodipine, when compared to perindopril plus HCTZ, reported Dike Ojji, MD, of the University of Abuja in Nigeria, at the American College of Cardiology annual meeting.

At baseline, the patients’ average 24-hour ambulatory systolic blood pressure (ASBP) was 146.7 mm Hg, but at 6 month follow up, the patients’ average 24-hour systolic blood pressure was 128.0 mm Hg. Taking amlodipine with either perindopril or HCTZ reduced ASBP by 17.1 mm Hg and 18.1 mm Hg, respectively.

Results of the study, which involved 621 patients in six countries (Nigeria, Cameroon, Uganda, Kenya, Mozambique, and South Africa), were also published in the New England Journal of Medicine.

Although there are numerous anti-hypertensive combination treatments, “the best combination for the black African population has not been identified and guideline recommendations are not consistent,” Ojji said here.

There is a high burden of hypertension and its related complications among this population. Patients usually require ≥2 antihypertensive agents to achieve current blood pressure guidelines. There are no randomized controlled trials comparing the 2-drug combination therapies as it relates to efficacy among this population, he noted.

Taking into account that amlodipine/perindopril and amlodipine/HCTZ had similar effects on blood pressure, “drug choice may be further influenced by side effect considerations – particularly cough and angioedema versus hypokalemia,” Ojji highlighted.

“Pending trial evidence comparing the effects of these combinations on cardiovascular outcomes, these unique data may be useful to influence antihypertensive drug selection for black patients, at least those from [sub-Saharan Africa],” he continued.

For example, amlodipine/HCTZ commonly leads to hypokalemia. So these patients should have their potassium levels monitored regularly and should be encouraged to eat foods high in potassium, he emphasized.

Africa is seeing a hypertension epidemic, said panel discussant Eileen Handberg, PhD, of the University of Florida in Gainesville, who credited Ojji and colleagues with putting together a representative sample for the trial. “When I first saw it I wondered if it would only be in one country, so I was very impressed that you were able to mobilize the trial across the other countries,” she said during a press conference.

“What I found interesting was the incidence of the large number of women you were able to enroll and the lack of treatment coming into it. So it alludes to the issue across the continent in terms of hypertension, so now we have 2 therapies. And it’s always with therapies about risk, benefit, and side effects, and so I think you have good data if you go on to do a mortality trial,” Handberg continued.

Handberg pointed out that having these side effect profiles “will certainly guide future trials as you look at how this is going to impact cardiovascular endpoints.”

“I think it is a great move forward, and I think we know cardiovascular disease is worldwide, and having a better understanding of exactly how it expresses itself is very important,” she continued.

Ojji’s group randomized patients 1:1:1 to the three drug combinations. Mean patient age was 51 and 63% were women.

Inclusion criteria were: female or male patients ages 30 to 79 years that also have either a sitting office systolic blood pressure (SBP) ≥150 and <180 mm Hg without antihypertensive treatment, or a sitting office SBP ≥140 and <160 mm Hg when taking one antihypertensive agent.

Exclusion criteria were: pregnancy, history of stroke, chronic kidney disease, or coronary heart disease, suspected or known secondary hypertension, a history showing intolerance to any of the study drugs, and other concomitant illness, mental or physical impairment that could interfere with conducting the investigation effectively.

Patients were assigned to take a daily regimen of 5 mg of amlodipine with 4 mg of perindopril; 4 mg of perindopril plus 12.5 mg of HCTZ; or 5 mg of amlodipine plus 12.5 mg of HCTZ for 2 months. Doses were then doubled for the remainder of the study period.

Participants’ 24-hour ASBP was measured at baseline and at the end of the 6-month study period. ASBP in the study involved having a small device attached to the body continuously for 24 to 48 hours to measure blood pressure at 15- to 30-minute intervals. Ambulatory monitoring gives a more accurate reading compared to a single measurement during a doctor’s visit, considering that blood pressure levels fluctuate throughout the day and night.

Patients were monitored over the phone in between follow-up visits every two months. They brought their prescriptions to their follow-up appointments, and clinic staff counted the pills to gauge adherence.

Adverse events numbered 39 each for the amlodipine/perindopril and amlodipine/HCTZ groups, and 28 patients in the perindopril-HCTZ group. As expected, hypokalemia was most common with amlodipine/HCTZ but only in 13 patients.

Limitations of the trial included its open-label design, and it is uncertain whether the findings from the study can be extrapolated to patients outside of sub-Saharan African, to black patients with diabetes, or “whether the results necessarily pertain to the use of other agents in the same drug classes or to the use of thiazide-like rather than thiazide diuretics,” Ojji and colleagues noted.