Abstract
Fast-absorbed and short-acting dihydropyridines (e.g., nifedipine capsules) cause intermittent hemodynamic effects associated with sympathetic hyperactivity. In contrast, long-acting dihydropyridines, such as nifedipine GITS and amlodipine, provide, during chronic treatment, stable hemodynamic effects with little or no activation of the sympathetic nervous system. This markedly different pattern of hemodynamic changes may explain why the short-acting drugs cause little to no regression of left ventricular hypertrophy, may make angina worse, and may negatively affect cardiac outcome, whereas the long-acting drugs decrease LV mass as anticipated from the fall in blood pressure and, at least in stable coronary artery disease, produce an outcome comparable with beta-blockers. In hypertension, beta-blocker treatment appears to be associated with a short fall in positive outcome, perhaps in part related to increased rates of sudden death. Such an adverse outcome may also be due to sympathetic hyperactivity, possibly during treatment via cardiac alpha-receptors, but also during the common short periods of noncompliance due to actual increased sympathetic responses. For both drug classes, we suggest that long-acting agents be considered, providing therapeutic coverage well beyond the normal dosing interval.