Granger Bradi B, Swedberg Karl, Ekman Inger, Granger Christopher B, Olofsson Bertil, McMurray John J V, Yusuf Salim, Michelson Eric L, Pfeffer Marc A
Duke University Medical Center and Duke University School of Nursing, Durham, NC, USA.
Lancet. 2005 Dec 10;366(9502):2005-11. doi: 10.1016/S0140-6736(05)67760-4.
Chronic heart failure (CHF) is an important cause of hospital admission and death. Poor adherence to medication is common in some chronic illnesses and might reduce the population effectiveness of proven treatments. Because little is known about adherence in patients with CHF and about the consequences of non-adherence, we assessed the association between adherence and clinical outcome in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme.
CHARM was a double-blind, randomised, controlled clinical trial, comparing the effects of the angiotensin receptor blocker candesartan with placebo in 7599 patients with CHF. Median follow-up was 38 months. The proportion of time patients took more than 80% of their study medication was defined as good adherence and 80% or less as poor adherence. We used a Cox proportional hazards regression model, with adherence as a time-dependent covariate in the model, to examine the association between adherence and mortality in the candesartan and placebo groups.
We excluded 187 patients because of missing information on adherence. In the time-dependent Cox regression model, after adjustment for predictive factors (demographics, physiological and severity-of-illness variables, smoking history, and number of concomitant medications), good adherence was associated with lower all-cause mortality in all patients (hazard ratio [HR] 0.65, 95% CI 0.57-0.75, p<0.0001). The adjusted HR for good adherence was similar in the candesartan (0.66, 0.55-0.81, p<0.0001) and placebo (0.64, 0.53-0.78, p<0.0001) groups.
Good adherence to medication is associated with a lower risk of death than poor adherence in patients with CHF, irrespective of assigned treatment. This finding suggests that adherence is a marker for adherence to effective treatments other than study medications, or to other adherence behaviours that affect outcome. Understanding these factors could provide an opportunity for new interventions, including those aimed at improving adherence.
慢性心力衰竭（CHF）是住院和死亡的重要原因。在一些慢性疾病中，药物依从性差很常见，这可能会降低已证实治疗方法的人群有效性。由于对CHF患者的依从性以及不依从的后果了解甚少，我们在CHARM（坎地沙坦治疗心力衰竭：死亡率和发病率降低评估）项目中评估了依从性与临床结局之间的关联。
CHARM是一项双盲、随机、对照临床试验，比较血管紧张素受体阻滞剂坎地沙坦与安慰剂对7599例CHF患者的疗效。中位随访时间为38个月。患者服用超过80%研究药物的时间比例被定义为依从性良好，80%或更低为依从性差。我们使用Cox比例风险回归模型，将依从性作为模型中的时间依赖性协变量，来检验坎地沙坦组和安慰剂组中依从性与死亡率之间的关联。
由于依从性信息缺失，我们排除了187例患者。在时间依赖性Cox回归模型中，在对预测因素（人口统计学、生理和疾病严重程度变量、吸烟史以及合并用药数量）进行调整后，依从性良好与所有患者全因死亡率较低相关（风险比[HR]0.65，95%CI 0.57 - 0.7 / 0.75，p<0.0001）。坎地沙坦组（0.66，0.55 - 0.81，p<0.0001）和安慰剂组（0.64，0.53 - 0.78，p<0.0001）中依从性良好的调整后HR相似。
CHF患者中，与依从性差相比，依从性良好与死亡风险较低相关，与分配的治疗无关。这一发现表明，依从性是除研究药物外对有效治疗依从性的一个标志，或者是对影响结局的其他依从行为的标志。了解这些因素可能为新的干预措施提供机会，包括旨在提高依从性的措施。
