By Will Boggs, MD
NEW YORK (Reuters Health) May 03 - For older patients with high-risk stage 2 hypertension and coronary artery disease (CAD), benazepril is best given with amlodipine rather than hydrochlorothiazide, researchers say.
The conclusions are drawn from a post hoc analysis of data from the randomized ACCOMPLISH trial, by Dr. George Bakris from The University of Chicago and colleagues.
"For CAD there is a stronger mechanistic reason to use amlodipine with an ACE (angiotensin converting enzyme) inhibitor than a diuretic because of its vascular effects on nitric oxide and improvement of vascular flow as an opposed to a thiazide diuretic that does not possess these effects," Dr. Bakris told Reuters Health in an email. "Thus, in these patients, unless needed for volume maintenance, diuretics should be third line."
Dr. Bakris and colleagues compared data on the effects of benazepril plus amlodipine or hydrochlorothiazide in 5,314 patients with and 6,192 patients without CAD.
The average follow-up was 36 months, according to a report online April 15 in the American Journal of Cardiology.
Among patients with CAD, rates of cardiovascular events were 16% with hydrochlorothiazide and 13% with amlodipine, a hazard reduction of 18% (p=0.0016).
The difference between the treatment arms was driven by a 34% lower fatal and nonfatal event rate in the amlodipine group compared to the thiazide group (p=0.0052).
Results were similar for patients without CAD: amlodipine was associated with a 19% lower event rate (p=0.026).
Overall, the composite secondary endpoint of cardiovascular mortality, myocardial infarction, and stroke occurred in significantly fewer amlodipine patients than thiazide patients (5.74% vs 8%; p=0.033). All-cause mortality was 23% lower in the amlodipine arm (p=0.042).
In patients without CAD, however, rates of cardiovascular mortality, myocardial infarction, and stroke did not differ significantly between the two treatments.
The rates of new-onset diabetes and chronic kidney disease progression did not differ between the two treatment arms in patients with CAD.
Both the primary endpoint and the secondary endpoint events were higher in the group of patients with CAD.
"Physicians should understand that single pill combinations as initial therapy are fully endorsed by guidelines around the world and in most patients with CAD, single pill combos are needed," Dr. Bakris concluded. "Given the vascular and now outcome benefits, a single pill combination of amlodipine-benazepril would be preferred over an ACE inhibitor-thiazide diuretic."
"I believe it should be the combination of choice," Dr. Dan Hackam from University of Western Ontario in London, who has published widely on hypertension and its treatment, told Reuters Health.
"If CAD patients are close to blood pressure targets (around 130/80-140/90), it might be wise to start with a single medication, such as an ACE inhibitor or calcium channel blocker, rather than both at once," Dr. Hackam said in an email. "Subsequently, if blood pressure is still high, the second agent could be added."
Dr. Brent M. Egan from the Medical University of South Carolina in Charleston, who has also extensive experience in hypertension, agreed. He told Reuters Health by email, "For hypertensive patients who require combination antihypertensive therapy beyond medications indicated for compelling indications, the combination of a renin-angiotensin system blocker with a calcium channel blocker, e.g., amlodipine, is an excellent choice."
"As physicians, we make decisions based on available information," Dr. Egan cautioned. "For example, we do not know if results would have been different in ACCOMPLISH if the ACE inhibitor had been paired with chlorthalidone or indapamide. The recommendation is based on data we have in a secondary data analysis. Grade B/C and not A."
Am J Cardiol 2013.
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