SAN FRANCISCO — Combining a calcium channel blocker and a lipid-lowering drug to treat 847 patients with both hypertension and hyperlipidemia reduced cardiovascular events more than either drug alone or placebo because of improvements in small artery elasticity, said Jay N. Cohn, M.D.
Preliminary results previously reported from the Efficacy and Safety of Atorvastatin Plus Amlodipine Versus Either Agent Alone in Patients with Concomitant Dyslipidemia and Hypertension (AVALON) trial showed a significantly lower rate of cardiovascular events with the combination therapy than with monotherapy or placebo, he said at the annual meeting of the American Society of Hypertension.
New data provide an explanation for the additive effects of the combined therapy. A nested substudy of 667 patients within the AVALON trial sequentially measured arterial wall compliance during treatment and found physiologic changes consistent with significantly greater improvements in small-artery compliance and better endothelial function in the combination therapy group, said Dr. Cohn, professor of medicine and director of the Rasmussen Center for Prevention of Cardiovascular Disease at the University of Minnesota, Minneapolis.
Pfizer Inc., which makes both amlodipine and atorvastatin, funded the study. Two of the investigators were Pfizer employees. Dr. Cohn is a consultant to and holds stock in Hypertension Diagnostics Inc., which makes the CV Profiler device that measured arterial compliance.
The CV Profiler uses a transducer placed over the radial artery of a patient at rest to measure pulse waves. A computer analysis of the waveforms assesses arterial stiffness. Separate short-term epidemiologic data suggest that lower small-artery elasticity increases the risk of heart attack, stroke, and other cardiovascular events, he said.
Dr. Cohn extrapolated from the current and previous data to suggest that reduced nitric oxide activity causes small-artery stiffness and that the combination of amlodipine and atorvastatin improves nitric oxide bioactivity. “I'm a firm believer that it's more than blood pressure which is playing a role in arterial health,” he said.
The results add to findings from a 10,000-patient substudy within the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showing that amlodipine plus atorvastatin therapy in older hypertensive patients with normal lipid levels reduced the rate of cardiovascular events, compared with monotherapy or placebo (Drugs 2004;2[64 suppl. 2]:43-60).