Regression of cardiac hypertrophy by 1,4 dihydropyridines in hypertensive patients.
BACKGROUND
Left ventricular hypertrophy (LVH) represents an important intermediate end-point for, for example, the progression to heart failure. The persistence or progression of LVH despite antihypertensive therapy probably reflects the persistence or activation of mechanisms that negatively affect the cardiovascular system and, consequently, long-term outcome.
Long-term treatment with rapid-onset (and usually short-acting) dihydropyridine calcium antagonists is significantly less effective than angiotensin converting enzyme (ACE) inhibition in reducing left ventricular mass (LVM) in hypertensive patients. Both intermittent, and probably only partial, blood pressure control and an increase in sympathetic activity resulting from rapid decreases in blood pressure following dosing with such calcium antagonists may contribute to this relative ineffectiveness. In contrast, more recent studies have demonstrated that the longer acting dihydropyridines can reduce LVM as effectively as ACE inhibitors.
Among the 1,4-dihydropyridines, drugs such as amlodipine and nifedipine in the gastrointestinal therapeutic system (GITS) maintain good blood pressure control over the full 24-h dosing period and do not cause dose-related increases in sympathetic activity. In contrast, extended-release felodipine has been shown to provide only intermittent blood pressure control, still leading to sympathetic activation. Notably, during short periods of noncompliance, blood pressure control is maintained with intrinsically long-acting agents such as amlodipine but not with slow-release formulations of short-acting agents such as nifedipine GITS.


CONCLUSIONS
It is possible that the rate of onset and duration of action of various dihydropyridines may be pivotal factors in determining their effects on cardiovascular outcomes. Thus, the least beneficial dihydropyridines may be rapid-onset, short-acting agents, such as nifedipine capsules, and the most beneficial may be the slow-onset, long-acting agents such as amlodipine.
Leenen
F H
FH
Division of Cardiology, University of Ottawa Heart Institute, Ontario, Canada.
D000959:Antihypertensive Agents / Q000627:therapeutic use; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology*; D004095:Dihydropyridines / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D012074:Remission Induction; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D004095:Dihydropyridines