CARVEDILOL - A REAPPRAISAL OF ITS PHARMACOLOGICAL PROPERTIES AND THERAPEUTIC USE IN CARDIOVASCULAR DISORDERS

Carvedilol competitively blocks beta 1, beta 2 and alpha 1 receptors. The drug lacks sympathomimetic activity and has vasodilating propertie s that are exerted primarily through alpha(1)-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosi s, arrhythmia and cell damage caused by oxidising free radicals, and t he drug has no adverse effects on plasma lipid profiles. Recent data h ave confirmed the antihypertensive efficacy of carvedilol in patients with mild to moderate essential hypertension. Carvedilol has similar e fficacy to other beta-blocking agents, calcium antagonist, ACE inhibit ors and hydrochlorothiazide. Carvedilol also improves exercise toleran ce and ischaemic symptoms in patients with stable angina pectoris. Sig nificant reductions in serious cardiac events after acute myocardial i nfarction and infrequency and severity of ischaemic events in patients with unstable angina have also been demonstrated. Interest in the use of carvedilol in patients with congestive heart failure (CHF) has cul minated in the publication of a cumulative analysis of data from 1094 patients with mild to severe CHF who participated in the US Carvedilol Heart Failure Study Program (4 trials). After a median follow-up of 6 .5 months, a significant overall reduction in mortality relative to pl acebo (3.2 vs 7.8%) was revealed in patients who had received carvedil ol 6.25 to 50 mg twice daily (plus diuretics and ACE inhibitors). All- cause mortality, risk of hospitalisation for cardiovascular reasons an d hospitialisation costs were also reduced significantly (by 65, 28% a nd 62%, respectively) in these trials. In addition, the Australia and New Zealand Heart Failure Research Collaborative Group showed a 26% re duction in the combined risk of death or hospitalisation with carvedil ol 12.5 to 50 mg/day relative to placebo after a mean 19-month follow- up period in 415 patients with CHF (relarive risk 0.74). Adverse event s with carvedilol appear to be less frequent than with other beta-bloc king agents, are dosage-related and are usually seen early in therapy. Events most commonly reported are related to the vasodilating (postur al hypotension, dizziness and headaches) and the beta-blocking (dyspno ea, bronchospasm, bradycardia, malaise and asthenia) properties of the drug. Carvedilol appears to data to have little effect on the inciden ce of worsening heart failure. Concomitant administration of carvedilo l with some medications requires monitoring. Carvedilol is therefore l ikely to have a beneficial role in the management of controlled CHF, b ut further clinical studies are required to show the place of beta-adr enoceptor blocking therapy in general in this indication, and the posi tion of carvedilol relative to other similar agents. Carvedilol is als o confirmed as effective in the management of mild to moderate hyperte nsion and ischaemic heart disease.