Korhonen Maarit Jaana, Ruokoniemi Päivi, Ilomäki Jenni, Meretoja Atte, Helin-Salmivaara Arja, Huupponen Risto
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Division of Pharmaceutical Outcomes and Policy, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):161-9. doi: 10.1002/pds.3936. Epub 2015 Dec 21.
We aimed to quantify for the first time the relationship between statin adherence and ischemic stroke (IS) in patients with diabetes.
Using Finnish health registers, we assembled a cohort of 52 868 statin initiators with diabetes in 1995-2006. We conducted a nested case-control analysis matching cases with IS with up to four controls for age, sex, date of statin initiation and follow-up duration. Adjusted rate ratios for IS were estimated with conditional logistic regression. Additional potential confounders were considered with inverse probability weighting and the role of unmeasured confounding using external adjustment. Statin adherence was measured as the proportion of days covered (PDC).
Among 1703 cases and 6799 controls, good adherence to statins (PDC ≥ 80%) was associated with a 23% decreased incidence of IS (95%CI 14-32%) compared with poor adherence (PDC < 80%). This association remained broadly unchanged when stratified by sex, age, history of atherosclerotic cardiovascular disease or IS. There was a dose-response relationship between adherence level and the risk of IS (RR 0.63 [0.53-0.75] for PDC ≥ 80% versus PDC < 20%, P for trend <0.0001). Among patients with good adherence, those initiating with low intensity statin therapy had a 15% lower incidence (95%CI 2-27%) and those initiating with moderate intensity therapy a 29% lower incidence (16-41%) of IS compared with those with poor adherence who initiated with low intensity therapy. Our sensitivity analyses supported the robustness of the results.
In diabetes, poor statin adherence may considerably increase the risk of IS both in primary and secondary prevention of IS.
我们旨在首次量化糖尿病患者中他汀类药物依从性与缺血性卒中(IS)之间的关系。
利用芬兰健康登记系统,我们纳入了1995年至2006年间开始使用他汀类药物的52868例糖尿病患者队列。我们进行了一项巢式病例对照分析,将IS患者与年龄、性别、他汀类药物起始日期和随访时间匹配的多达4名对照进行匹配。使用条件逻辑回归估计IS的调整率比。通过逆概率加权考虑其他潜在混杂因素,并使用外部调整评估未测量混杂因素的作用。他汀类药物依从性通过覆盖天数比例(PDC)来衡量。
在1703例病例和6799例对照中,与依从性差(PDC<80%)相比,他汀类药物依从性良好(PDC≥80%)与IS发病率降低23%相关(95%CI 14-32%)。按性别、年龄、动脉粥样硬化性心血管疾病或IS病史分层时,这种关联大致保持不变。依从性水平与IS风险之间存在剂量反应关系(PDC≥80%与PDC<20%相比,RR 0.63[0.53-0.75],趋势P<0.0001)。在依从性良好的患者中,与起始低强度他汀类药物治疗且依从性差的患者相比,起始低强度他汀类药物治疗的患者IS发病率降低15%(95%CI 2-27%),起始中等强度治疗的患者IS发病率降低29%(16-41%)。我们的敏感性分析支持了结果的稳健性。
在糖尿病患者中,他汀类药物依从性差可能会显著增加IS一级和二级预防中的发病风险。