Survivors Of Acute Infarction Research Articles

Antiarrhythmic drugs

Pharmacologic therapy of cardiac arrhythmias remains in a state of considerable flux. New findings from relevant experimental models, controlled clinical trials, and meta-analyses of randomized clinical trials need to be integrated into appropriate algorithms for the control of ventricular and supraventricular tachyarrhythmias. The Cardiac Arrhythmia Suppression Trial I drew attention to the fact that certain sodium-channel blockers (class Ic agents) were powerful premature ventricular contraction suppressants but produced an excess mortality in survivors of acute infarction, raising the issue whether the premature ventricular contraction hypothesis was valid. Its validity is further challenged by the results of the Cardiac Arrhythmia Suppression Trial II with moricizine, which also increased mortality although it differs electrophysiologically from class Ic agents. From meta-analytic studies, it has become clear that most, if not all, sodium-channel blockers increase mortality given the appropriate clinical milieu. In contrast, controlled and uncontrolled clinical trials have indicated that in different subsets of patients, β-blockers reduce sudden death and total cardiac mortality. Data also suggest that a reduction in sudden death might be effected by amiodarone and possibly by sotalol, both of which act by lengthening repolarization and refractoriness, properties modified by, sympathetic modulation. The role of sympathetic modulation may now be determined with studies involving pure class III agents. Preliminary data from the Electrophysiologic Study versus Electrocardiographic Monitoring trial in manifest ventricular tachycardia and aborted sudden death indicated that the two techniques were statistically indistinguishable in predicting drug responses and that sotalol was significantly-superior to class I agents in reducing arrhythmia recurrence in responders. The emerging data again emphasize the need for a major reorientation in our approach to antiarrhythmic therapy, taking cognizance of sudden death and mortality as endpoints and not merely surrogate endpoints and risk markers for guiding treatment. Such a reorientation of antiarrhythmic therapy with drugs should shift attention away from the concept of delaying conduction to that of prolonging refractoriness, with a focus on β-blockers and class III agents that have antiadrenergic properties, such as sotalol and amiodarone.

Sotalol

Sotalol is a beta-adrenoceptor blocking agent devoid of intrinsic sympathomimetic activity, membrane stabilising actions and cardioselectivity. It lengthens repolarisation and the effective refractory period in all cardiac tissues independently of its antiadrenergic properties. Combining Class II and Class III antiarrhythmic properties, sotalol can be given either intravenously or orally and its pharmacokinetic properties permit long dosing (once or twice daily) intervals. Controlled and uncontrolled studies have established the efficacy of sotalol in mild-to-moderate essential hypertension and in angina of effort. Sotalol reduces anginal frequency and glyceryl trinitrate (nitroglycerin) consumption and increases exercise capacity during treadmill stress tests. In addition, although there is evidence that the drug reduces reinfarction rate in survivors of acute infarction, the data for reduction in sudden death rates in these patients are not as compelling as for other beta-blockers. However, comparative and additional long term studies are required before an accurate assessment of the use of sotalol in these disorders can be made. When used in the treatment of mild-to-moderate hypertension sotalol is more effective than placebo and comparable to other beta-blockers in reducing elevated blood pressures. In addition, a synergistic antihypertensive response is achieved when sotalol is combined with hydrochlorothiazide. Still, additional well-controlled comparative studies are required before the value of sotalol relative to other drug treatment regimens in the management of hypertension can be made. In preliminary studies sotalol appeared effective in most forms of supraventricular tachyarrhythmias with its effects being similar to those of other beta-blockers. However, preliminary data indicate that sotalol is likely to be more effective than than conventional beta-blockers in converting atrial flutter and fibrillation to sinus rhythm and maintaining stability post-conversion. Sotalol also appears to be a promising agent in the control of ventricular arrhythmias. In suppressing premature ventricular contractions it is at least as effective as procainamide. In ventricular tachycardia and fibrillation, intravenous sotalol (1.5 mg/kg), prevents reinduction by programmed electrical stimulation in 40 to 50% of cases if double stimuli are used. Both prevention of reinducible arrhythmia and the suppression of spontaneous arrhythmias on Holter recordings are predictive of a long term favourable clinical outcome. In patients with reduced ejection fractions, sotalol depresses ventricular function less than conventional beta-blockers.(ABSTRACT TRUNCATED AT 400 WORDS)