Use of Compliance Measures in an Analysis of the Effect of Diltiazem on Mortality and Reinfarction After Myocardial Infarction

Abstract

A clinical trial efficacy analysis based on actual drug usage is described. The influence of diltiazem therapy on mortality and reinfarction in the multicenter diltiazem post-infarction trial (MDPIT) is analyzed using records for drug discontinuation and reinitiation; the results are then compared with the previously published “intention to treat” analysis. As expected, previously reported beneficial effects of diltiazem therapy in patients without pulmonary congestion and previously reported harmful effects in patients with pulmonary congestion are strengthened for patients while on study medication; both effects are weakened for those not on study medication. It is also shown that for patients assigned to placebo, being on or off study medication is a powerful prognostic indicator of subsequent outcome events, especially among patients with pulmonary congestion. Analysis of discontinuation rates suggested that patients assigned to diltiazem therapy were likely to discontinue trial medication earlier than were patients assigned to placebo, especially for those patients with pulmonary congestion.

KEY WORDS:

• Clinical trial
• Efficacy analysis
• Proportional hazards
• Survival analysis
• Time-dependent covariates