Obias-Manno D, Friedmann E, Brooks M M, Thomas S A, Haakenson C, Morris M, Wimbush F, Somelofski C, Goldner F
Washington Hospital Center, Washington, DC, USA.
Ann Epidemiol. 1996 Mar;6(2):93-101. doi: 10.1016/1047-2797(95)00134-4.
Patient adherence to therapy is essential to assess treatment efficacy, particularly in clinical trials. Active treatment usually is expected to benefit patients. The healthy adherer effect, the association or greater adherence to all health-promoting behaviors, including medication 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 (CAST), a placebo-controlled double-blind clinical trial of post-myocardial 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 adherence to survival from a different perspective. We consider whether adherence to active treatment was related to arrhythmic mortality and whether a healthy adherer effect might counteract the effect of treatment on mortality among patients taking active medication. Adherence (average pill count) at the first follow-up visit did not differ in the active treatment (92.2%, standard deviation (SD) = 11.97, n = 574) and placebo (90.8%, SD = 13.66, n = 579) groups. In a Cox proportional hazard regression model, medication adherence predicted arrhythmic mortality among the active (P < 0.0062) but not the placebo medication group. The effect of adherence on arrhythmic mortality was significant beyond the effects of ejection fraction, race, spouse, smoking status, diuretic medication, and history of MI. A 10% increase in adherence led to more than a threefold increase of risk of arrhythmic death. The design of the CAST, which included a titration phase, may have tended to select 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 counterbalanced the effect of the active medication.
患者对治疗的依从性对于评估治疗效果至关重要，尤其是在临床试验中。积极治疗通常预期会使患者受益。健康依从者效应，即对包括药物治疗和对健康的整体关注在内的所有促进健康行为的关联或更高依从性，解释了在多项临床试验的积极治疗组和安慰剂治疗组中，依从性更高的患者生存率更高的现象。心律失常抑制试验（CAST）是一项针对无症状室性心律失常的心肌梗死（MI）后患者的安慰剂对照双盲临床试验，其中积极药物治疗（恩卡尼或氟卡尼）导致死亡率增加，该试验提供了一个从不同角度研究依从性与生存率关系的机会。我们考虑对积极治疗的依从性是否与心律失常死亡率相关，以及健康依从者效应是否可能抵消积极药物治疗对患者死亡率的影响。在首次随访时，积极治疗组（92.2%，标准差（SD）=11.97，n = 574）和安慰剂组（90.8%，SD = 13.66，n = 579）的依从性（平均药丸计数）没有差异。在Cox比例风险回归模型中，药物依从性可预测积极治疗组中心律失常死亡率（P < 0.0062），但不能预测安慰剂治疗组。依从性对心律失常死亡率的影响在射血分数、种族、配偶、吸烟状况、利尿剂使用和心肌梗死病史的影响之外仍然显著。依从性增加10%会导致心律失常死亡风险增加三倍以上。CAST的设计包括一个滴定阶段，可能倾向于选择相对依从的患者，因为只有那些心律失常被积极药物抑制的患者才被随机纳入试验。数据不支持CAST中有强大的健康依从者效应。本研究中没有证据表明健康依从者效应抵消了积极药物的作用。
