New research suggests that the pharmacological effects of taking medications such as statins and beta-blockers as prescribed following a heart attack is associated with living longer, according to a study in the January 10 issue of JAMA.
Clinical trials have demonstrated that selected medications reduce the risk of cardiovascular death. However, their projected survival impact in the real world is less known, in part because of variations in drug adherence, according to background information in the article. Although it is known that adherence to evidence-based medications 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 behaviors (healthy adherer effect).
Jeppe N. Rasmussen, M.D., of the University of Toronto, and colleagues examined the relationship between drug adherence and death following acute myocardial infarction (AMI; heart attack). To help evaluate whether this relationship was more attributable to drug effects rather than to healthy adherer effects, the researchers examined 3 medication classes, 2 of which are associated with proven mortality benefits (statins and beta-blockers); the third medication class (calcium channel blockers) was examined as a control given the absence of documented post-heart attack survival advantages. The study included 31,455 elderly heart attack survivors between 1999 and 2003 in Ontario. All patients filled a prescription for statins, beta-blockers, or calcium channel blockers. Patient adherence was subdivided into 3 categories: high (proportion of days covered, 80 percent or greater), intermediate (proportion of days covered, 40 percent - 79 percent), and low (proportion of days covered, less than 40 percent).
Among patients who used statins, mortality was greatest for low adherers (deaths in 261/1,071; 24 percent), intermediary for intermediate adherers (deaths in 472/2,407; 20 percent), and lower for high adherers (2,310/14,345; 16 percent).
The researchers found that after adjustment for baseline patient characteristics, compared with those with high levels of adherence to statins, the adjusted risk of death was 12 percent higher among patients with intermediate adherence and was 25 percent higher among patients with poor adherence. A similar but less pronounced dose-response-type adherence-mortality association was observed for beta-blockers. There was no relationship between calcium channel blocker adherence and mortality.
"Our study has important clinical and policy implications. The graded dose-response-type relationship underscores the importance of drug adherence when projecting the survival benefits of evidence-based therapies in the population. Moreover, the long-term prognostic importance associated with shorter-term adherence patterns (as measured within the first year of AMI discharge) may have clinical applications for integration into cardiovascular prognostic indexes-indexes that might then be used to better delineate high-risk vulnerable populations who may benefit from more intensive secondary prevention initiatives. Finally, given their associated effects on survival, the inclusion of adherence data will have important cost-effective implications and should be considered routinely in pharmacoeconomic analyses," the authors write.
"In conclusion, the differential class effects of drug adherence on long-term survival following MI suggest that adherence-related mortality benefits associated with evidence-based pharmacotherapies are mediated by drug effects more so than by generic healthy adherer behavioral attributes. The beneficial biological effects associated with higher drug adherence on survival underscores the need to optimize adherent patient behavior patterns to maximize the survival gains of evidence-based therapies in real-world populations, which may be enhanced through the implementation of pharmacy or other preventive care programs," the researchers conclude.
Materials provided by JAMA and Archives Journals. Note: Content may be edited for style and length.
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