Safety and Effectiveness of Statins for Primary Prevention in Adults With Type 1 Diabetes: An Emulation

Abstract

Background: There is no consensus for using statins for primary prevention of cardiovascular disease (CVD) and all-cause mortality in adults with type 1 diabetes mellitus (T1DM), because no randomized controlled trial has exclusively investigated statins in this population. Objectives: In this study, the authors sought to evaluate the long-term risks and benefits of statins for primary prevention in adults with T1DM. Methods: We performed a sequential target trial emulation comparing statin initiation vs noninitiation using UK primary care data from the IQVIA Medical Research Data database. Persons aged 25 to 84 years with a diagnosis record of T1DM with prescription of insulin from January 2005 to December 2016 were included if they had baseline low-density lipoprotein-cholesterol (LDL-C) ≥2.6 mmol/L (100 mg/dL) or non-high-density lipoprotein cholesterol ≥3.4 mmol/L (130 mg/dL). Persons with preexisting coronary artery disease, myocardial infarction, stroke, heart failure, myopathy, liver disease, rheumatic heart disease, schizophrenia or cancer were excluded. Main outcome measures were all-cause mortality, major CVD and adverse events (myopathy and liver dysfunction). We estimated 10-year absolute risk differences (RDs) for the observational analogues of the intention-to-treat (ITT) and per-protocol (PP) effects. Results: We included 4,176 statin initiator (mean age of 45 years, 33.1% <40 years, 40.6% female) and 16,704 noninitiator person-trials with median follow-up of 6 years. Compared with noninitiation, statins were associated with reductions in all-cause mortality (RDITT: −1.66% [95% CI: −2.79% to −0.45%]; RDPP: −3.48% [95% CI: −4.68% to −2.07%]) and major CVD (RDITT: −1.63% [95% CI: −2.57% to −0.53%]; RDPP: −2.69% [95% CI: −4.00% to −1.22%]). Some analyses suggested a slight association with increased risk of liver dysfunction but no association with myopathy. In subgroup analyses, absolute risk reductions were generally larger in women, persons ≥40 years of age, persons with baseline LDL-C ≥3.4 mmol/L (130 mg/dL), and persons with a higher predicted cardiovascular risk. Conclusions: Among adults with T1DM, statin initiation for primary prevention was associated with reductions in all-cause mortality and major CVD with a very low risk of adverse effects. The differences in absolute risk reductions can help guide personalized statin treatment decisions in T1DM.