ADHERENCE AND ARRHYTHMIC MORTALITY IN THE CARDIAC-ARRHYTHMIA SUPPRESSION TRIAL (CAST)

Patient adherence to therapy is essential to assess treatment efficacy , particularly in clinical trials. Active treatment usually is expecte d to benefit patients. The healthy adherer effect, the association or greater adherence to all health-promoting behaviors, including medicat ion and overall concern for health, explains the improved survival of more adherent patients in both active and placebo medication groups of several clinical trials. The Cardiac Arrhythmia Suppression Trial (CA ST), a placebo-controlled double-blind clinical trial of post-myocardi al infarction (MI) patients with asymptomatic ventricular arrhythmias, in which active medication (encainide or flecainide) led to increased mortality, provided an opportunity to examine the relationship of adh erence to survival from a different perspective. We consider whether a dherence to active treatment was related to arrhythmic mortality and w hether a healthy adherer effect might counteract the effect of treatme nt on mortality among patients taking active medication. Adherence (av erage pill count) at the first follow-up visit did not differ in the a ctive treatment (92.2%, standard deviation (SD) = 11.97, n = 574) and placebo (90.8%, SD = 13.66, n = 579) groups. In a Cox proportional haz ard regression model, medication adherence Predicted arrhythmic mortal ity among the active (P < 0.0062) but not the placebo medication group . The effect of adherence on arrhythmic mortality was significant beyo nd the effects of ejection fraction, race, spouse, smoking status, diu retic medication, and history of MI. A 10% increase in adherence led t o more than a threefold increase of risk of arrhythmic death. The desi gn of the CAST, which included a titration phase, may have tended to s elect relatively adherent patients since only those whose arrhythmias were suppressed with active medication were randomized into the trial. The data do not support a strong healthy adherer effect in the CAST. There was no evidence in this study that a healthy adherer effect coun terbalanced the effect of the active medication.