Effectiveness and Safety of Statins in Type 2 Diabetes According to Baseline Cardiovascular Risk

Background: Whether statins benefit patients with type 2 diabetes mellitus (T2DM) with low predicted 10-year cardiovascular risk is uncertain. Objective: To evaluate the effectiveness and safety of statin initiation for primary prevention among adults with T2DM stratified by predicted 10-year risk for cardiovascular disease (CVD). Design: Cohort study using target trial emulation. Setting: U.K. primary care using the IQVIA Medical Research Data database. Participants: Persons aged 25 to 84 years with a diagnosis of T2DM between 2005 and 2016 and no history of coronary artery disease, myocardial infarction, stroke, heart failure, myopathy, liver disease, rheumatic heart disease, schizophrenia, or cancer. Intervention: Statin initiation versus noninitiation, with estimation of the observational analogues of the intention-to-treat effect. Statin initiators were propensity score–matched to noninitiators in a 1:4 ratio within 4 QRISK3 strata of 10-year predicted cardiovascular risk: low (<10%), intermediate (10% to 19%), high (20% to 29%), and very high (≥30%). Measurements: Absolute risk differences (RDs) and risk ratios (RRs) at 10 years of follow-up for all-cause mortality and major CVD, as well as myopathy and liver dysfunction. Results: Statin initiation was associated with reductions in all-cause mortality and major CVD across QRISK3 strata. In the low-risk stratum, RDs and RRs were −0.53% (95% CI, −0.90% to −0.08%) and 0.80 (95% CI, 0.67 to 0.97), respectively, for all-cause mortality and −0.83% (95% CI, −1.28% to −0.34%) and 0.78 (95% CI, 0.66 to 0.91), respectively, for major CVD. A small increased risk for myopathy was observed in the moderate-risk stratum only, and there was no associated increased risk for liver dysfunction in any stratum. Limitations: Unmeasured confounding and underascertainment of some hospitalization outcomes. Conclusion: Statin use in T2DM for primary prevention was associated with reductions in all-cause mortality and major CVD across the full spectrum of predicted cardiovascular risk. Primary Funding Source: National Natural Science Foundation of China.