Study Finds High Aspirin and Clopidogrel Resistance Rates in Stable Coronary Artery Disease Patients
A recent prospective study published in the Indian Heart Journal in March 2026 reveals striking antiplatelet resistance in stable coronary artery disease, with 30.5% of patients non-responsive to aspirin and 36.8% to clopidogrel. These high rates of drug resistance highlight a critical vulnerability in secondary cardiovascular prevention.
Antiplatelet therapy with aspirin and clopidogrel prevents ischemic events in CAD, yet response varies due to drug resistance; despite Western research, scarce South Asian data creates a clinical gap regarding resistance patterns in Indian patients. To address this, Dr. Nirmal Ghati and colleagues from the Department of Cardiology at All India Institute of Medical Sciences (AIIMS), New Delhi, evaluated antiplatelet resistance prevalence and predictors in stable CAD.
Therefore, the prospective study evaluated platelet reactivity using light transmittance platelet aggregometry in 151 stable coronary artery disease patients receiving aspirin and/or clopidogrel at AIIMS, New Delhi, excluding those with prior stroke, bleeding history, or abnormal platelet counts. Over a mean follow-up of 13.4 months, researchers tracked primary major adverse cardiovascular events alongside secondary clinical outcomes.
Key clinical findings of the study include:
- High Resistance Prevalence: Investigators observed complete aspirin resistance in 7.3% and semi-resistance in 23.2% (30.5% total), alongside complete clopidogrel resistance in 29.2% and semi-resistance in 7.6% (36.8% total), with dual resistance at 7.6%.
- Diabetic Link to Aspirin: Researchers identified diabetes mellitus as a significant univariate predictor of aspirin resistance (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1–4.4; p=0.03), with higher glycated hemoglobin levels in resistant subjects (7.3% vs. 6.7%; p=0.05).
- Familial Clopidogrel Risk: Authors determined that a positive family history of CAD independently predicted clopidogrel resistance on multivariable analysis (OR 5.9, 95% CI 1.4–25.8; p=0.02).
- Inter-Drug Non-Responsiveness: Analysis demonstrated that clopidogrel resistance independently predicted aspirin resistance on multivariable regression (OR 20.2, 95% CI 7.9–51.9; p<0.01).
- Hematologic Correlations: Evaluation revealed that lower hemoglobin (12.9 vs. 13.7 g/dL; p=0.03) and elevated erythrocyte sedimentation rate (22.8 vs. 19.3 mm/hr; p=0.04) were significantly associated with clopidogrel resistance in univariate testing.
The results suggest that while aspirin and clopidogrel resistance are common among stable CAD patients—affecting 30.5% on aspirin and 36.8% on clopidogrel—their impact on major adverse cardiovascular events (9.3% in aspirin-resistant vs. 9.5% in responders) remains statistically inconclusive due to low event rates.
Thus, the study concludes clinicians should recognize that clinical risk profiles like diabetes mellitus and a family history of coronary artery disease may signal antiplatelet non-responsiveness, highlighting the need for careful risk stratification and tailored antiplatelet therapy in high-risk patients.
Although limited by a single-center design, a modest sample size, and brief follow-up, these findings emphasize the need for larger, adequately powered prospective multicenter trials to establish the prognostic impact of antiplatelet resistance in South Asian populations.
Reference
Ghati N, Narang R, Pati HP, Mishra AK, Basha A. Prevalence and predictors of aspirin and clopidogrel resistance by light transmittance platelet aggregometry in stable coronary artery disease. Indian Heart Journal. 2026;78(2):179-186.
