SAN FRANCISCO — For left ventricular mass to be reduced in patients with hypertension, getting the blood pressure to goal is what matters, not which antihypertensives you use, according to a phase III study.
The findings challenge conventional wisdom that credits renin angiotensin-aldosterone system inhibitors with being the most effective antihypertensives for left ventricular hypertrophy (LVH) regression, followed by calcium channel blockers, then beta-blockers, then diuretics.
“It turns out that's not the case,” Dr. Alan B. Miller said at the annual meeting of the American Society of Hypertension. “It probably doesn't matter what drug you use. If you get to the blood pressure goal, good things happen—in this case, left ventricular regression, and I suspect clinical outcomes will follow,” said Dr. Miller, professor of cardiology at the University of Florida, Jacksonville.
The multicenter, double-blind study included 287 patients with class 1 or class 2 hypertension and documented left ventricular hypertrophy who were being treated with 20 mg/day of the ACE inhibitor lisinopril. Patients were randomized to adjunctive therapy with up to 80 mg/day of the nonselective beta-blocker/alpha-1 blocker carvedilol CR (Coreg), up to 100 mg/day of the beta-blocker atenolol, or up to 40 mg/day of lisinopril without beta-blockade. Some patients also required concomitant hydrochlorothiazide or hydrochlorothiazide plus amlodipine to control hypertension.
During 12 months of treatment, 73% of the carvedilol/lisinopril group, 67% of the atenolol/lisinopril group, and 79% of the high-dose lisinopril group reached recommended blood pressure goals (less than 130/80 mm Hg for the 25% of patients who had diabetes, or less than 140/90 mm Hg for other patients).
Follow-up echocardiography or cardiac MRI showed left ventricular mass regressed by a mean 6.3 g/m
The CLEVER results support the idea that “if you lower blood pressure enough, you'll regress left ventricular hypertrophy regardless of what you use,” said session moderator Dr. Marvin Moser of Yale University, New Haven, Conn.
Rates of side effects were low, as might be expected with these established medications, Dr. Miller said. Cough was somewhat more common (17%) in the high-dose lisinopril group than in the atenolol (5%) or carvedilol (9%) groups. Fatigue was more common with atenolol (17%) than in the other two groups (7% each). Headaches were reported by 12%-15% of patients.
Dr. Miller has been a consultant and speaker for GlaxoSmithKline, which markets Coreg and funded the study, and has been a speaker for AstraZeneca and received research funds from Merck. Dr. Moser reported having no conflicts of interest.
'If you get to the blood pressure goal, good things happen—in this case, left ventricular regression.' DR. MILLER