Effects of antihypertensive drugs on vascular remodeling: do they predict outcome in response to antihypertensive therapy?
Remodeling of large and small arteries in hypertension contributes to elevation of blood pressure, and may participate in the complications of hypertension. Large arteries exhibit increased lumen size, thickened media with increased collagen deposition, and decreased compliance, which contributes to raised systolic blood pressure and pulse pressure. In small (resistance) arteries smooth muscle cells are restructured around a smaller lumen, without true hypertrophy, particularly in milder forms of hypertension, whereas in severe forms and in secondary hypertension hypertrophic remodeling has been reported. Endothelial dysfunction occurs in many patients, with prevalence similar to that of left ventricular hypertrophy. Treatment with angiotensin-converting enzyme inhibitors, angiotensin receptor subtype 1 antagonists and long-acting calcium channel blockers has corrected changes in large and small arteries in hypertensive patients. Treatment with beta-blockers did not modify either structure or function of small arteries. Improved outcomes were reported in clinical trials with drugs that exert vascular protective effects, such as angiotensin-converting enzyme inhibitors and angiotensin receptor subtype 1 antagonists, as well as with those that do not appear to improve vascular structure or function. Recent trials suggest that these different drugs may provide similar benefits essentially through blood pressure lowering, although some minor differences between drugs have been noted. For example, the alpha-blocker doxasozin has been associated with worse outcomes (heart failure) than have diuretics. That hard end-point clinical trials have not demonstrated any advantages of agents with vasculoprotective properties may relate in part to the relatively short duration of some of these multicenter trials (3-5 years). Another contributing factor may be the low number of events with each drug class in the longer trials. Thus, current evidence does not support the rational expectation that vasculoprotective antihypertensive agents will be associated with better outcomes in hypertensive patients, possibly because of limitations of these trials.
Schiffrin
E L
EL
Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montréal, Québec, Canada. schiffe@ircm.qc.ca
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001808:Blood Vessels / Q000187:drug effects; D002986:Clinical Trials as Topic; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D011379:Prognosis
D000959:Antihypertensive Agents