Impact of Statin Nonacceptance on Cardiovascular Outcomes in Patients With Diabetes.

Background: Many patients with diabetes do not accept statin therapy despite being at increased risk for cardiovascular events compared with the general population. The effects of delaying statin therapy are not well-understood.

Methods: This is a retrospective cohort study that followed adults with diabetes and no preexisting atherosclerotic cardiovascular disease at the Mass General Brigham integrated health system between 2000 and 2018. The exposure was immediate versus delayed statin acceptance by patients who were recommended statin therapy. The primary outcome was the composite incidence of myocardial infarction and ischemic stroke.

Results: Among the 7239 study patients, the median age was 55.0 years, and 52.0% were women. Within this cohort, 1280 (17.7%) delayed statin therapy by a mean±SD of 2.7±3.1 years. Patients who delayed statin therapy had higher mean low-density lipoprotein cholesterol levels while they were not prescribed a statin (126.4 versus 99.2 mg/dL, P<0.001). The cumulative 10-year rate of myocardial infarctions and ischemic strokes was 6.4% for patients who initiated statins immediately versus 8.5% for patients who delayed statin therapy (P=0.001). In a multivariable analysis adjusted for demographic characteristics and comorbidities, statin nonacceptance was an independent risk factor for myocardial infarction and ischemic stroke (hazard ratio [HR], 1.49 [95% CI, 1.16-1.90]; P=0.002). Mediation analysis showed that greater low-density lipoprotein cholesterol exposure induced a higher incidence of adverse cardiovascular events (HR, 1.62 [95% CI, 1.46-1.80]; P<0.001).

Conclusions: Among patients with diabetes, patients who delayed statin therapy had a significantly higher cardiovascular risk; this relationship was mediated by higher low-density lipoprotein cholesterol levels. These findings underscore the importance of timely lipid-lowering for this high-risk patient population and can help guide decision-making by patients and clinicians.