Molokhia Mariam, McKeigue Paul, Curcin Vasa, Majeed Azeem
Department of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.
PLoS One. 2008 Jun 25;3(6):e2522. doi: 10.1371/journal.pone.0002522.
Statins are widely used as a cholesterol lowering medication, reduce cardiovascular mortality and morbidity in high risk patients; and only rarely cause serious adverse drug reactions (ADRs). UK primary care databases of morbidity and prescription data, which now cover several million people, have potential for more powerful analytical approaches to study ADRs including adjusting for confounders and examining temporal effects.
Case-crossover design in detecting statin associated myopathy ADR in 93, 831 patients, using two independent primary care databases (1991-2006). We analysed risk by drug class, by disease code and cumulative year, exploring different cut-off exposure times and confounding by temporality.
Using a 12 and 26 week exposure period, large risk ratios (RR) are associated with all classes of statins and fibrates for myopathy: RR 10.6 (9.8-11.4) and 19.9 (17.6-22.6) respectively. At 26 weeks, the largest risks are with fluvastatin RR 33.3 (95% CI 16.8-66.0) and ciprofibrate (with previous statin use) RR 40.5 (95% CI 13.4-122.0). AT 12 weeks the differences between cerivastatin and atorvastatin RR for myopathy were found to be significant, RR 2.05 (95% CI 1.2-3.5), and for rosuvastatin and fluvastatin RR 3.0 (95% CI 1.6-5.7). After 12 months of statin initiation, the relative risk for myopathy for all statins and fibrates increased to 25.7 (95% CI 21.8-30.3). Furthermore, this signal was detected within 2 years of first events being recorded. Our data suggests an annual incidence of statin induced myopathy or myalgia of around 11.4 for 16, 591 patients or 689 per million per year.
There may be differential risks associated with some classes of statin and fibrate. Myopathy related to statin or fibrate use may persist after a long exposure time (12 months or more). These methods could be applied for early detection of harmful drug side effects, using similar primary care diagnostic and prescribing data.
他汀类药物作为一种降胆固醇药物被广泛使用，可降低高危患者的心血管死亡率和发病率，且很少引起严重药物不良反应（ADR）。英国涵盖数百万人的初级医疗发病率和处方数据库，有潜力采用更强大的分析方法来研究药物不良反应，包括对混杂因素进行调整和研究时间效应。
采用病例交叉设计，利用两个独立的初级医疗数据库（1991 - 2006年），对93831例患者检测他汀类药物相关的肌病不良反应。我们按药物类别、疾病编码和累积年份分析风险，探索不同的暴露时间截断点以及时间混杂因素。
采用12周和26周的暴露期，所有类别的他汀类药物和贝特类药物与肌病相关的风险比（RR）都很高：分别为RR 10.6（9.8 - 11.4）和19.9（17.6 - 22.6）。在26周时，风险最高的是氟伐他汀RR 33.3（95%可信区间16.8 - 66.0）和环丙贝特（曾使用他汀类药物）RR 40.5（95%可信区间13.4 - 122.0）。在12周时，发现西立伐他汀和阿托伐他汀与肌病相关的RR差异显著，RR 2.05（95%可信区间1.2 - 3.5），瑞舒伐他汀和氟伐他汀的RR为3.0（95%可信区间1.6 - 5.7）。他汀类药物开始使用12个月后，所有他汀类药物和贝特类药物导致肌病的相对风险增加到25.7（95%可信区间21.8 - 30.3）。此外，在首次记录事件的2年内检测到了这种信号。我们的数据表明，16591例患者中他汀类药物诱发的肌病或肌痛年发病率约为11.4，即每年每百万中有689例。
某些类别的他汀类药物和贝特类药物可能存在不同的风险。与他汀类药物或贝特类药物使用相关的肌病在长时间暴露（12个月或更长时间）后可能持续存在。利用类似的初级医疗诊断和处方数据，这些方法可用于早期发现有害药物副作用。
