Diabetes Research Centre, University of Leicester, Leicester, United Kingdom.
Outcomes Research, Outcomes Insights, Inc, Westlake Village, California.
JAMA Netw Open. 2018 Dec 7;1(8):e185554. doi: 10.1001/jamanetworkopen.2018.5554.
Both adherence and treatment intensity can alter the effectiveness of lipid-lowering therapy in routine clinical practice.
To evaluate the association of adherence and treatment intensity with cardiovascular outcomes in patients with documented cardiovascular disease (CVD), type 2 diabetes without CVD or chronic kidney disease (CKD), and CKD without CVD.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using the Clinical Practice Research Datalink from January 2010 through February 2016. United Kingdom primary care was the setting. Participants were newly treated patients who received their first statin and/or ezetimibe prescription between January 1, 2010, and December 31, 2013, plus an additional prescription for statins and/or ezetimibe during the following year.
Adherence was assessed annually using the proportion of days covered, with adherent defined as a proportion of days covered of 80% or higher. Treatment intensity was classified according to guidelines based on the expected percentage of low-density lipoprotein cholesterol (LDL-C) reduction as low (<30% reduction), moderate (30% to <50% reduction), or high (≥50% reduction). Adherence and treatment intensity were multiplied to create a combined measure, reflecting treatment intensity after accounting for adherence.
Composite end point of cardiovascular death or hospitalization for myocardial infarction, unstable angina, ischemic stroke, heart failure, or revascularization. Hazard ratios (HRs) were estimated against patients not treated for 1 year or longer.
Among a total of 29 797 newly treated patients, there were 16 701, 12 422, and 674 patients with documented CVD, type 2 diabetes without CVD or CKD, and CKD without CVD, respectively; mean (SD) ages were 68.3 (13.2), 59.3 (12.4), and 67.3 (15.1) years, and male proportions were 60.6%, 55.0%, and 47.0%. In the documented CVD cohort, patients receiving high-intensity therapy were more likely to be adherent over time (84.1% in year 1 and 72.3% in year 6) than patients receiving low-intensity therapy (57.4% in year 1 and 48.4% in year 6). Using a combined measure of adherence and treatment intensity, a graded association was observed with both LDL-C reduction and CVD outcomes: each 10% increase in the combined measure was associated with a 10% lower risk (HR, 0.90; 95% CI, 0.86-0.94). Adherent patients receiving a high-intensity regimen had the lowest risk (HR, 0.60; 95% CI, 0.54-0.68) vs patients untreated for 1 year or longer. Findings in the other 2 cohorts were similar.
Results of this study demonstrate that the lowest cardiovascular risk was observed among adherent patients receiving high-intensity therapy, and the highest cardiovascular risk was observed among nonadherent patients receiving low-intensity therapy. Strategies that improve adherence and greater use of intensive therapies could substantially improve cardiovascular risk.
在常规临床实践中，依从性和治疗强度均可改变降脂治疗的效果。
评估在有记录的心血管疾病（CVD）、无 CVD 或慢性肾脏病（CKD）的 2 型糖尿病以及无 CVD 的 CKD 患者中，依从性和治疗强度与心血管结局的相关性。
设计、环境和参与者：这是一项回顾性队列研究，使用了 2010 年 1 月至 2016 年 2 月间的临床实践研究数据链接。英国初级保健是该研究的背景。参与者为新接受他汀类药物和/或依折麦布处方的患者，这些患者在 2010 年 1 月 1 日至 2013 年 12 月 31 日之间首次接受他汀类药物和/或依折麦布处方，随后在次年又接受了他汀类药物和/或依折麦布的处方。
每年使用比例覆盖天数评估依从性，将比例覆盖天数达到 80%或更高定义为依从性。根据预期 LDL-C 降低百分比（<30%、30%-<50%和≥50%）的指南将治疗强度分为低、中、高三级。将依从性和治疗强度相乘，得出一个综合指标，反映了在考虑到依从性后治疗的强度。
心血管死亡或因心肌梗死、不稳定型心绞痛、缺血性卒、心力衰竭或血运重建而住院的复合终点。对未治疗 1 年或更长时间的患者进行了风险比（HR）估计。
在总共 29797 名新接受治疗的患者中，分别有 16701 名、12422 名和 674 名患者有记录的 CVD、无 CVD 或 CKD 的 2 型糖尿病和无 CVD 的 CKD；平均（SD）年龄分别为 68.3（13.2）岁、59.3（12.4）岁和 67.3（15.1）岁，男性比例分别为 60.6%、55.0%和 47.0%。在有记录的 CVD 队列中，接受高强度治疗的患者随着时间的推移更有可能保持依从性（第 1 年为 84.1%，第 6 年为 72.3%），而接受低强度治疗的患者则不然（第 1 年为 57.4%，第 6 年为 48.4%）。使用依从性和治疗强度的综合指标，观察到 LDL-C 降低与 CVD 结局之间存在分级关联：综合指标每增加 10%，风险就会降低 10%（HR，0.90；95%CI，0.86-0.94）。与未治疗 1 年或更长时间的患者相比，依从性高且接受高强度治疗方案的患者风险最低（HR，0.60；95%CI，0.54-0.68）。在其他 2 个队列中的发现类似。
这项研究的结果表明，依从性高且接受高强度治疗的患者心血管风险最低，而不依从且接受低强度治疗的患者心血管风险最高。提高依从性和更多使用强化治疗的策略可以显著降低心血管风险。
