Infarct size reduction: A review of the clinical trials

The most important finding to emerge from this review of experimental and clinical studies is that the earlier therapy is begun after the onset of symptoms of acute MI, the greater the potential for reduction of infarct size and possibly mortality. It is difficult to define a precise time after which therapy would not have an effect, since the clinical trials for each drug group vary significantly in respect to time of therapy initiation. In experimental studies, major salvage of ischemic myocardium occurs when the drug is given within two hours of coronary artery occlusion. If drug therapy is begun four to six hours postocclusion, then only minor or no reductions in infarct size will occur. The ability of any drug or intervention to reduce infarct size in humans would be optimized if therapy were begun less than four hours of onset of symptoms. With the realization of the wavefront phenomenon and the potential salvage of myocardium at risk with reperfusion, the introduction of reperfusion in the clinical setting with thrombolytic agents or other procedures becomes highly desirable. Clot-selective thrombolytic agents, such as tissue plasminogen activator, diminish adverse effects and high costs of intracoronary thrombolytic therapy or PTCA. Consequently, it is probable that the initial procedure of choice would be the use of clot-selective thrombolytic therapy. Thrombolytic therapy only lyses thrombi and does not affect the underlying causes of the coronary artery occlusion. Therefore, therapy to reduce the chances of reinfarction and death must also be initiated. Percutaneous transluminal coronary angioplasty, in selected patients, should reduce the reocclusion rate. Beta-adrenoceptor blocking agents appear to be an excellent therapy for reducing mortality when administered chronically; these agents reduce myocardial oxygen consumption and reverse the imbalance between oxygen supply and oxygen demand caused by activation of the sympathetic nervous system and actions of catecholamines. Since thrombus formation has occurred at least once in patients who survive an MI, it is probable that the conditions for thrombus formation still exist. Therefore, institution of antiplatelet aggregating drugs, such as aspirin, would seem to be an appropriate prophylactic regimen. Beta blockers and possibly nitroglycerin have desirable effects when thrombolysis is unavailable. The efficacy of calcium-channel blocking agents on reduction of infarct size appears to be limited, although in the setting of stable and unstable angina postinfarction, these agents can play an important role. There appears to be no evidence that nitroprusside or anti-inflammatory agents is useful in patients with uncomplicated MI. The potential adverse effects of reperfusion become more important with the increasing use of coronary reperfusion to salvage ischemic myocardium. Therefore, combining thrombolytic therapy with free radical scavenging agents to attenuate the effects of oxygen radicals produced with reperfusion may be the optimal treatment to reduce infarct size.