What Should the Study Design Be to Test New Antiarrhythmic Drugs in Patients with Acute Myocardial Infarction, Digitalis Toxicity and Other Acute Problems

Abstract

In the setting of acute myocardial infarction the largest single use of antiarrhythmic drug therapy is for the prevention of ventricular fibrillation. In this setting drug efficacy cannot be judged in a single patient and can only be inferred from well controlled clinical trials. Traditionally lidocaine has been the most widely utilized drug for this indication. We can learn about the potential flaws to be avoided in antiarrhythmic drug trials by examining the previously performed clinical trials of lidocaine in acute myocardial infarction. Table 1 summarizes some of the larger series evaluating lidocaine efficacy in this setting. None of these studies were able to show a beneficial effect of lidocaine in preventing ventricular fibrillation until the study of Lie et al. The pitfalls of all of these studies (except that of Lie and coworkers) may be listed as follows:

• 1. Most studies were based on the assumption that warning arrhythmias identified patients at risk of ventricular fibrillation and therefore the endpoint of therapy was suppression of warning arrhythmias. They permitted placebo treated or control patients to crossover to lidocaine therapy once warning arrhythmias occurred.

• 2. There was inadequate knowledge of the pharmacokinetics of lidocaine. This resulted in several problems:

  • a. No initial loading bolus.

  • b. Inadequate maintenance infusion rate.

  • c. Failure to achieve or document therapeutic lidocaine plasma concentrations.

• 3. In many instances there was delay in patient arrival at the hospital or in institution of drug therapy so that the period of highest risk of ventricular fibrillation had passed.