This article is more than 5 years old. Information may no longer be current.
Combination therapy with amlodipine effective in sub-Saharan black adults
NEW ORLEANS — A combination of amlodipine and one of hydrochlorothiazide or perindopril showed efficacy in treating hypertension in black adults in sub-Saharan Africa compared with a hydrochlorothiazide-perindopril, according to findings presented at the American College of Cardiology Scientific Session.
Dike B. Ojji, MD, PhD, and colleagues sought to compare the efficacy of the combinations on mean 24-hour ambulatory systolic BP.
“Although there are many possible antihypertensive combination therapies, the best combination for the black African population has not been identified and guideline recommendations are inconsistent,” Ojji, of the department of medicine, Faculty of Clinical Sciences at the University of Abuja in Nigeria, said during the presentation. “This is in spite of a high burden of hypertension and its complication in this population.”
The researchers performed a randomized, single-blind, three-group trial in six sub-Saharan African countries on patients with uncontrolled hypertension.
Patients received, over a 2-month span, a daily regimen of 5 mg of amlodipine plus 12.5 mg of hydrochlorothiazide, 5 mg of amlodipine plus 4 mg of perindopril or 4 mg of perindopril plus 12.5 mg of hydrochlorothiazide. Doses were doubled for an additional 4 months.
The primary endpoint was change in 24-hour ambulatory systolic BP between baseline and 6 months.
Ojji and colleagues identified 621 patients who were monitored for 24-hour BP monitoring at baseline and at 6 months (mean age, 51 years; 63% women).
Patients who took the combination of amlodipine plus hydrochlorothiazide and amlodipine plus perindopril had a lower 24 ambulatory systolic BP compared with patients using perindopril and hydrochlorothiazide (between-group difference in change from baseline = –3.14 mm Hg; 95% CI, –5.9 to –0.38; P = .03; and –3 mm Hg; 95% CI, –5.8 to –0.2; P = .04, respectively), the researchers wrote.
Ojji and colleagues found no difference between the amlodipine plus hydrochlorothiazide regimen group and the amlodipine plus perindopril group (between group difference = –0.14 mm Hg; 95% CI, –2.9 to 2.61).
“Pending trial evidence comparing the effects of these combinations on cardiovascular outcomes, these may be useful to influence antihypertensive drug selection for black patients, at least in sub-Saharan Africa,” Ojji said during the presentation. – by Earl Holland Jr.
Reference:
Ojji DB, et al. Late-Breaking Clinical Trials IV. Presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.
Disclosure: Ojji reports no relevant financial disclosures.
Perspective
Back to Top
I think the biggest take home is that amlodipine seems to be a powerful drug in an African population.
There was a portion of patients with diabetes, but whether withholding an ACE inhibitor is something we should do in diabetics from a renal protection standpoint is an issue.
I was incredibly impressed by the cohort consisting of more than 60% women because we rarely see a study with that ratio.
It’s a study that was done in sub-Saharan Africa, so there are questions about whether the results apply to the black population in the United States or elsewhere, because there are different issues and different risk factors, and lifestyles may be different in one country vs. another.
We tend to use these drugs, right now, in our black population for the reasons stated in the study, particularly the side effects of ACE inhibitors. These are of grave concern in the African-American population because these patients get more angioedema due to ACE inhibitors.
Using a diuretic is certainly beneficial. A lot of the studies previously used chlorthalidone.
In the real world, many physicians don’t use chlorthalidone. They extrapolate that chlorthalidone is the same as hydrochlorothiazide.
I’m not 100% sure that this entirely applies to us, but there’s certainly things we are doing that are confirmed in this study, which reaffirms that this type of calcium channel blocker is beneficial in an African-American population and using that drug first to treat hypertension is powerful.
Perspective
Back to Top
The findings of the CREOLE study showed that several combination drug approaches to BP management can be successfully deployed and managed in African patients. Moreover, it did show differences in efficacy between the three groups both by office readings and by ambulatory BP monitoring.
The findings support what was found in the ACCOMPLISH trial showing that a calcium channel blocker plus an ACE inhibitor was better than the calcium channel blocker plus hydrochlorothiazide for BP control in the confines of the study.
ACCOMPLISH ensured equal control and demonstrated better outcomes with a calcium channel blocker plus an ACE inhibitor in those who were at a lower BMI level.
It is also a help to the WHO initiative, in conjunction with the CDC and the AHA, working on global normalization of BP through usage of generic combination therapies.
This is a short-term study that demonstrated superior efficacy at 6 months of the two arms over the ACE inhibitor plus hydrochlorothiazide arm.
Outcomes will ultimately be the important thing here.
Having to check for metabolic side effects reduces some of the attractiveness of diuretics and the cosmetic issues with lower leg edema on amlodipine are important to some patients.
A remaining question is, will these patients continue to adhere to the regimen for the years necessary to see benefit?
Perspective
Back to Top
Patients of African descent often have resistant and difficult to control primary hypertension.
In the CREOLE study, findings reinforced what our current ACC/American Heart Association guidelines state regarding management of hypertension. The study used amlodipine as a primary agent for the management of hypertension.
Inclusion criteria into the study showed BP readings greater than 140 mm Hg systolic.
Researchers used combination therapy, which is also recommended in the guideline of two agents as initial therapy.
It showed equal efficacy of amlodipine plus hydrochlorothiazide or amlodipine plus perindopril in lowering BP more effectively than perindopril and hydrochlorothiazide.
This again reinforces the guidelines stating that ACE inhibitors or angiotensin receptor blockers are not as efficacious in patients of African descent.
The findings also reinforce the role of initiating multiple agents early in the treatment course in this subset population.
Perspective
Back to Top
CREOLE shows us the superiority of a two-drug regimen for high blood pressure in Africa with either amlodipine plus hydrochlorothiazide or amlodipine plus perindopril that may be extrapolated for use for difficult to treat hypertension in an African-American population as well.
Similar to the barbershop study last year, this may be helpful in reducing hypertension, MI and stroke in an American population.