In patients with diabetes and without obstructive coronary artery disease (CAD), statin use — but not aspirin use — reduced the risk for major adverse cardiovascular events (MACE) as assessed by coronary angiography (CAG), according to research results published in the European Heart Journal Cardiovascular Pharmacotherapy.

Although statins are the first-line choice of lipid-lowering drugs, lipid-lowering therapies or aspirin is not generally recommended for people with diabetes at low risk for cardiovascular events. However, the efficacy of aspirins and statins for patients with diabetes with angiographic absence of CAD has not been evaluated in a randomized setting, according to the researchers.

Using regional and national health care registries in Denmark, researchers conducted a cohort study to test their hypothesis that neither aspirin nor statin therapy would reduce the risk for MACE in patients with diabetes but without obstructive CAD.

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Adult patients with diabetes but without CAD or nonobstructive CAD who underwent CAG screening between 2003 and 2016 were included in the study cohort. They were stratified by aspirin or statin treatment with 4124 participants in each group. The primary study outcome was MACE, defined as myocardial infarction, ischemic stroke, or all-cause death. Separate evaluations were conducted for rates of cardiovascular death, all-cause death, or hospitalization for bleeding associated with aspirin therapy.

Within the 2 study cohorts, 60% of participants in 1 group were receiving aspirin, and 71% of the other group were receiving statin treatment. The median follow-up time was 4.9 years.

Patients who received aspirin treatment 6 months after CAG were more likely to be older and more were women compared with patients not treated with aspirin. These patients were also more likely to have hypertension and heart failure, and were treated more frequently with statins, noninsulin diabetes medication, and antihypertensive drugs.

Patients in the statin group were also older and more were women compared with nontreated patients. Treatment with statins was more frequently associated with hypertension, but less frequently associated with heart failure and renal disease, according to researchers.

Overall, the 10-year cumulative MACE incidence was similar in patients treated with aspirin and in nontreated patients (21.3% vs 21.8%). No difference was noted in 10-year MACE when the average treatment effects of aspirin were estimated (HRIPTW 1.01; 95% CI, 0.82-1.25). Results were similar for cardiovascular death and all-cause death, and hospitalizations for bleeding were not increased in the aspirin-treated group.

Statin treatment following CAG was associated with a 10-year reduced risk for MACE vs nontreated patients (24.6% vs 37.2%; HRIPTW 0.58; 95% CI, 0.48-0.70), driven by lower risk for myocardial infarction and death. Investigators found no significant effect of high intensity vs moderate intensity statin treatment.

Among a group of patients undergoing an elective procedure resulting from stable angina pectoris, aspirin did not reduce MACE. Investigators also noted a “more modest MACE reduction” associated with statin treatment compared with the main analysis, and a subgroup analysis of patients with type 2 diabetes “yielded similar results.”

Study limitations include a lack of access to low-density lipoprotein cholesterol values, potential residual confounding and confounding by indication leading to bias in the results, and the measurement of drug exposure by prescription redemption.

“Statins, but not aspirin, reduced cardiovascular risk as assessed by CAG in patients with diabetes and without obstructive CAD,” the researchers wrote. “However, aspirin did not increase hospitalizations for bleeding.”

“Unless proven otherwise by future randomized trials, our results suggest that statin treatment should be recommended to patients with diabetes, even with documented absence of CAD,” they concluded. “Continued aspirin treatment cannot be discouraged based on our results, but should be carefully weighed by patients in consultation with their physicians in the context of their individual risk profiles.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Olesen KKW, Heide-Jørgensen U, Thim T, et al. Statin but not aspirin treatment is associated with reduced cardiovascular risk in patients with diabetes without obstructive coronary artery disease. Eur Heart J Cardiovasc Pharmacother. Published online May 14, 2021. doi:10.1093/ehjcvp/pvab040

This article originally appeared on The Cardiology Advisor