Mortality and Adherence to Pharmacotherapy After Acute Myocardial Infarction

Abstract

To the Editor: In their study of adherence to evidencebased pharmacotherapy and long-term mortality after acute myocardial infarction (AMI), Dr Rasmussen and colleagues suggest that the relationship between high adherence and lower mortality is due to an active drug effect rather than to a “healthy adherer” effect. Adherence to placebo has also been associated with lower mortality, suggesting that other factors may also be important. One of these factors may be depression, since depression is associated with poor adherence and with increased mortality after MI. If depression rather than drug effect were the causative agent, then the relationship of adherence to mortality should exist whether or not the drug is active. Rasmussen et al conclude that they are not observing a healthy adherer effect because high adherence to -blockers and statins was associated with improved survival, whereas high adherence to calcium channel blockers (CCBs) was not. The authors use adherence to CCBs as a control since CCBs have no proven survival advantages after an MI. However, immediaterelease nifedipine is contraindicated (class III) in the treatment of ST-elevation myocardial infarction (STEMI), and diltiazem and verapamil are contraindicated in STEMI with left ventricular systolic dysfunction and heart failure. In nonSTEMI, immediate-release dihydropyridine CCBs are contraindicated (class III) in the absence of a -blocker, and extended-release nondihydropyridine CCBs have a class IIb recommendation. If CCBs are harmful, the lack of a relationship between adherence and mortality could potentially represent the healthy adherer effect counterbalancing the harmful effect of CCBs. Rasmussen et al do not report specifically on depression, but the patients in their study with low adherence had a significantly greater prevalence of psychiatric illness than those with high adherence. While depression is associated with poor adherence and both are associated with increased mortality, how depression and adherence may interact to influence mortality has not been studied. Adherence may mediate the relationship between depression and mortality. Alternatively, there may be an interaction such that patients with both depression and poor adherence have higher mortality than patients with either alone. An analysis that attempted to delineate the relationship between depression, adherence, and mortality would be of great interest, as it could inform clinicians and researchers where to focus their efforts to achieve the most benefit in the treatment of depression, improvement of adherence, or both. Kapil Parakh, MD, MPH kparakh1@jhmi.edu David E. Bush, MD Roy C. Ziegelstein, MD Department of Medicine Johns Hopkins University School of Medicine Baltimore, Md Brett D. Thombs, PhD Department of Psychiatry McGill University Montreal, Quebec James A. Fauerbach, PhD Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine