No 'Healthy Adherer Effect' Found In Post-MI Patients

TORONTO, Jan. 9 -- Heart attack survivors who conscientiously take prescribed statins or beta-blockers live longer than those who don't, but that's not so for compliant patients on calcium channel inhibitors, according to researchers here reported.

The observational study suggested the so-called "healthy adherer effect" was not a factor for post-MI patients taking calcium channel blockers. It also confirmed that statins and beta-blockers work in the "real world" as well as in clinical trials, said David A. Alter, M.D., Ph.D., of the Institute for Clinical Evaluative Sciences.

Poor adherence to statins was associated with a 25% increased mortality risk, while poor adherence to beta-blockers increased the risk of dying by 13%, Dr. Alter and colleagues reported in the Jan. 10 issue of the Journal of the American Medical Association.

If the healthy adherer effect was involved in the observed mortality benefits for statins and beta blockers, there should have been some mortality benefit seen among adherent patients on calcium channel inhibitors as well, the authors reasoned.

But adherence to calcium channel inhibitors-"considered a control given the absence of clinical trial-proven survival benefits"-was not significantly linked to mortality risk, they found.

"Although it is known that adherence to evidence-based pharmacotherapy predicts better survival, no population outcome study has attempted to differentiate whether these associations are attributable to the drug's biological responsiveness (drug effect) or to the adoption of healthier lifestyles that often accompany adherent behavior (healthy adherer effect)," the authors wrote.

The population-based, longitudinal study included more than 30,000 patients 65 and older who had survived an acute myocardial infarction between 1990 and 2003. All were on one of the three drugs.

Patients were subdivided into three adherence groups: high (an 80% compliance rate or more), intermediate (40% to 80% compliance), or low (less than 40% compliance). Patients were followed for a median of 2.4 years.

Among statin users, low adherers were significantly more likely to die than high adherers (hazard ratio=1.25; 95% confidence interval=1.09 to 1.42; P=.002). Intermediate compliance was also riskier (HR=1.12; 95% CI=1.01 to 1.25; P=.03).

There was a similar though less significant trend among patients on beta-blockers. The hazard ratio for low adherers was 1.13 (95% CI=1.03 to 1.25; P=.008). For intermediate adherence, the ratio was 1.01 (95% CI=0.93 to 1.09; P=.84). Beta blockers may be less effective than statins in long-term, post-myocardial infarction patients, the authors noted.

The mortality analyses were adjusted for potential confounders such as illness severity, co-morbidities, and social and demographic variables.

"Ours was the first study to our knowledge to demonstrate the existence of drug class-specific adherence-mortality gradients among real-world populations, a finding consistent with the biological responsiveness related to the pharmacologic classes themselves," the authors said.

The study "underscores the need to optimize adherent patient behavior patterns to maximize the survival gains of evidence-based therapies in real-world populations," the authors concluded.

A chief limitation of the study is that it measured adherence indirectly by checking whether patient prescriptions had been filled rather than using a more direct method such as counting pills, the authors said.

In addition, the study did not take lifestyle factors such as diet, smoking, or exercise into account, they said.