Comparison of short-acting versus extended-release nifedipine: Effects on hemodynamics and sympathetic activity in patients with stable coronary artery disease

Abstract

We investigated the impact of short-acting and extended release nifedipine on sympathetic activity using radiotracer methodology in patients with stable coronary artery disease in order to more accurately document the response of the sympathetic nervous system to different formulations of this dihydropyridine calcium channel antagonist. Participants were randomized to placebo, short-acting or extended release nifedipine for 7–10 days. On the final day, systemic blood pressure, cardiac filling pressures, cardiac output, plasma norepinephrine (NE) and total body NE spillover were measured at baseline (time 0) and repeated at intervals for 6 hours. There were no differences in baseline measures between groups. Following the morning dose of study medication there were no changes in hemodynamics or sympathetic activity in the placebo group. However, there was a significant fall in blood pressure and a significant increase in total body NE spillover in both nifedipine groups. Importantly, the increase in sympathetic activity in response to short-acting nifedipine began earlier (30 minutes) and was much greater than that observed in the extended release group, which occurred later (270 minutes). These findings confirm that sustained therapy with nifedipine is associated with activation of the sympathetic nervous system which is dependent on the pharmacokinetics of the formulation.