Absolute risk reductions with statin therapy increased steadily as baseline cardiovascular risk rose in adults with type 2 diabetes, according to a recent study.

Statin initiation for primary prevention in adults with type 2 diabetes was associated with lower risks of all-cause mortality and major cardiovascular disease across all categories of baseline predicted cardiovascular risk, including patients with a 10-year cardiovascular risk below 10%. In the lowest-risk group, statin initiation was associated with a 10-year absolute risk reduction (ARR) of 0.53 percentage points for all-cause mortality and 0.83 percentage points for major cardiovascular disease (CVD), corresponding to risk ratios of 0.80 and 0.78, respectively. ARRs increased with higher baseline risk, reaching 4.30 percentage points for all-cause mortality and 4.57 percentage points for major CVD among patients with a predicted 10-year risk of 30% or higher. Across QRISK3 risk strata, analyses showed no increase in liver dysfunction and low absolute rates of statin-associated myopathy, with small risk increases observed only in selected strata.

These findings were derived from a population-based target trial emulation study using the IQVIA Medical Research Data UK database, which includes longitudinal primary care electronic health records. Researchers identified adults aged 25 to 84 years with type 2 diabetes diagnosed between 2005 and 2016 who had no prior history of CVD or major statin contraindications. The observational study, published in Annals of Internal Medicine, compared statin initiation with noninitiation for primary prevention and applied a target trial framework to reduce biases common to observational research, including immortal time and selection bias.

Participants were stratified by baseline 10-year cardiovascular risk using the QRISK3 algorithm into 4 prespecified categories: less than 10%, 10% to 19%, 20% to 29%, and 30% or higher. Within each stratum, statin initiators were propensity score–matched to noninitiators in a one-to-four ratio using demographic variables, comorbid conditions, medication use, and clinical measures. Follow-up extended up to 10 years, with outcomes assessed using inverse probability–weighted pooled logistic regression models to estimate observational analogues of intention-to-treat effects.

The primary outcomes were all-cause mortality and major CVD, defined as a composite of myocardial infarction, stroke, and heart failure. Median follow-up was 75 to 81 months, depending on treatment group. Per-protocol analyses showed larger ARRs than intention-to-treat analyses across QRISK3 strata, consistent with greater estimated benefit among patients who remained on statin therapy. Among patients with baseline predicted risk below 10%, reductions in mortality and cardiovascular events were observed primarily in those with elevated low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol levels.

The researchers noted several limitations. Residual confounding could not be excluded because of the observational design, particularly from unmeasured lifestyle factors such as diet and physical activity. Some outcomes, including statin-associated muscle symptoms and hospitalizations, may have been ascertained inadequately or misclassified in primary care records. The study population was drawn exclusively from the UK and was predominantly White patients, which may limit generalizability to other populations where QRISK3 has not been validated. Incomplete capture of treatment adherence and over-the-counter statin use may also have affected exposure classification.

In discussing the clinical implications, the researchers stated that “clinicians should consider the benefits of using statins in all adults with T2DM even when short-term predicted CVD risk is low,” noting that their findings suggest potential benefit beyond conventional risk thresholds for primary prevention.

The study was funded by the National Natural Science Foundation of China Excellent Young Scientists Fund. Full disclosures can be found in the published study.

Source: Annals of Internal Medicine