Rasmussen Jeppe N, Chong Alice, Alter David A
Institute of Clinical Evaluative Sciences, Toronto, Ontario, Canada.
JAMA. 2007 Jan 10;297(2):177-86. doi: 10.1001/jama.297.2.177.
The extent to which drug adherence may affect survival remains unclear, in part because mortality differences may be attributable to "healthy adherer" behavioral attributes more so than to pharmacological benefits.
To explore the relationship between drug adherence and mortality in survivors of acute myocardial infarction (AMI).
DESIGN, SETTING, AND PARTICIPANTS: Population-based, observational, longitudinal study of 31 455 elderly AMI survivors between 1999 and 2003 in Ontario. All patients filled a prescription for statins, beta-blockers, or calcium channel blockers, with the latter drug considered a control given the absence of clinical trial-proven survival benefits.
Patient adherence was subdivided a priori into 3 categories--high (proportion of days covered, > or =80%), intermediate (proportion of days covered, 40%-79%), and low (proportion of days covered, <40%)--and compared with long-term mortality (median of 2.4 years of follow-up) using multivariable survival models (and propensity analyses) adjusted for sociodemographic factors, illness severity, comorbidities, and concomitant use of evidence-based therapies.
Among statin users, compared with their high-adherence counterparts, the risk of mortality was greatest for low adherers (deaths in 261/1071 (24%) vs 2310/14,345 (16%); adjusted hazard ratio, 1.25; 95% confidence interval, 1.09-1.42; P = .001) and was intermediary for intermediate adherers (deaths in 472/2407 (20%); adjusted hazard ratio, 1.12; 95% confidence interval, 1.01-1.25; P = .03). A similar but less pronounced dose-response-type adherence-mortality association was observed for beta-blockers. Mortality was not associated with adherence to calcium channel blockers. Moreover, sensitivity analyses demonstrated no relationships between drug adherence and cancer-related admissions, outcomes for which biological plausibility do not exist.
The long-term survival advantages associated with improved drug adherence after AMI appear to be class-specific, suggesting that adherence outcome benefits are mediated by drug effects and do not merely reflect an epiphenomenon of "healthy adherer" behavioral attributes.
药物依从性对生存率的影响程度尚不清楚，部分原因是死亡率差异可能更多归因于“健康依从者”的行为特征，而非药理益处。
探讨急性心肌梗死（AMI）幸存者中药物依从性与死亡率之间的关系。
设计、地点和参与者：基于人群的观察性纵向研究，研究对象为1999年至2003年安大略省的31455名老年AMI幸存者。所有患者均开具了他汀类药物、β受体阻滞剂或钙通道阻滞剂的处方，鉴于后者缺乏经临床试验证实的生存益处，将其视为对照药物。
患者依从性预先分为3类——高（覆盖天数比例≥80%）、中（覆盖天数比例40%-79%）和低（覆盖天数比例<40%）——并使用多变量生存模型（和倾向分析），在对社会人口学因素、疾病严重程度、合并症和循证疗法的同时使用情况进行调整后，与长期死亡率（中位随访2.4年）进行比较。
在他汀类药物使用者中，与高依从性者相比，低依从性者的死亡风险最高（261/1071例死亡（24%） vs 2310/14345例死亡（16%）；调整后的风险比为1.25；95%置信区间为1.09-1.42；P = 0.001），中等依从性者的死亡风险处于中间水平（472/2407例死亡（20%）；调整后的风险比为1.12；95%置信区间为1.01-1.25；P = 0.03）。β受体阻滞剂也观察到类似但不太明显的剂量反应型依从性-死亡率关联。死亡率与钙通道阻滞剂的依从性无关。此外，敏感性分析表明药物依从性与癌症相关入院之间无关联，对于这些结果不存在生物学合理性。
AMI后改善药物依从性带来的长期生存优势似乎具有药物类别特异性，这表明依从性的结果益处是由药物效应介导的，而不仅仅反映“健康依从者”行为特征的附带现象。
