Concomitant nitrates enhance clopidogrel response during dual anti-platelet therapy

• Published in: International journal of cardiology 2016-01, Vol.203, p.877-881
• Main Authors: Lee, Dong Hyun, Kim, Moo Hyun, Guo, Long Zhe, De Jin, Cai, Cho, Young Rak, Park, Kyungil, Park, Jong Sung, Park, Tae-Ho, Serebruany, Victor
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adverse events; Aged; Aged, 80 and over; Blood Platelets - drug effects; Cardiovascular; Clinical outcomes; Clopidogrel; Coronary Artery Disease - physiopathology; Coronary Artery Disease - surgery; Drug Therapy, Combination; Dual anti-platelet therapy; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nitrates; Nitrates - administration & dosage; Percutaneous Coronary Intervention; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Function Tests; Platelet reactivity; Prospective Studies; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Time Factors; Treatment Outcome; Young Adult
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2015.11.068

Abstract Background Despite advances in modern anti-platelet strategies, clopidogrel still remains the cornerstone of dual anti-platelet therapy (DAPT) in patients undergoing percutaneous coronary interventions (PCI). There is some inconclusive evidence that response after clopidogrel may be impacted by concomitant medications, potentially affecting clinical outcomes. Sustained released nitrates (SRN) are commonly used together with clopidogrel in post-PCI setting for mild vasodilatation and nitric oxide-induced platelet inhibition. Methods We prospectively enrolled 458 patients (64.5 ± 9.6 years old, and 73.4% males) following PCI undergoing DAPT with clopidogrel and aspirin. Platelet reactivity was assessed by the VerifyNow™ P2 Y12 assay at the maintenance outpatient setting. Results Concomitant SRN (n = 266) significantly (p = 0.008) enhanced platelet inhibition after DAPT (251.6 ± 80.9 PRU) when compared (232.1 ± 73.5 PRU) to the SRN-free (n = 192) patients. Multivariate logistic regression analysis with the cut-off value of 253 PRU for defining heightened platelet reactivity confirmed independent correlation of more potent platelet inhibition during DAPT and use of SRN (Relative risk = 1.675; Odds ratio [1.059–2.648]; p = 0.027). In contrast, statins, calcium-channel blockers, beta blockers, angiotensin receptor blockers, ACE-inhibitors, diuretics, and anti-diabetic agents did not significantly impact platelet inhibition following DAPT. Conclusion The synergic ability of SRN to enhance response during DAPT may have important clinical implications with regard to better cardiovascular protection, but extra bleeding risks, requiring further confirmation in a large randomized study.