Effect of Calcium Channel Blockers on Antiplatelet Activity of Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: Insights from the PTRG-DES Consortium

J Cardiovasc Pharmacol Ther. 2024 Jan-Dec:29:10742484241298150. doi: 10.1177/10742484241298150.

Abstract

Aims: Calcium channel blockers (CCBs) are frequently co-administered with clopidogrel in cardiovascular disease. Although an inhibitory drug interaction exists between them, comprehensive large-scale studies for its validation are lacking. We investigated interactions between CCBs and clopidogrel using a large-scale national registry of patients who underwent percutaneous coronary intervention (PCI). Methods and Results: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test consortium investigates the association between platelet function test and long-term prognosis during dual antiplatelet therapy including clopidogrel in patients using drug-eluting stents. We compared the ex vivo platelet reactivity using the VerifyNow P2Y12 test and clinical outcomes between CCB users and non-users. Between 2003 and 2018, 11 714 patients were enrolled and categorized into two groups according to CCB usage. A composite endpoint encompassing all-cause mortality, myocardial infarction, stent thrombosis, or stroke was defined as a major adverse cardiac and cerebrovascular event (MACCE). During the 5-year follow-up period, no significant differences were observed in P2Y12 reaction units (215.8 ± 84.7 vs 218.4 ± 76.7, P = .156), MACCEs, major bleeding, or high platelet reactivity rates, even after adjusting for propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). When limited to the high platelet reactivity cohort (≥252 PRU), the results remained consistent for MACCE [PSM-adjusted, HR: 0.923 (0.644-1.323), P-value .663; IPTW-adjusted, HR: 1.300 (0.822-2.056), P-value .262]. Conclusions: CCB and clopidogrel co-administration does not appear to significantly impact clopidogrel responsiveness or clinical outcomes. Despite these promising results, further investigation may be warranted. Clinical trial registration: Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028.

Keywords: calcium channel blockers; cardiovascular disease; clopidogrel; long-term prognosis; platelet function test.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Calcium Channel Blockers* / therapeutic use
  • Clopidogrel* / administration & dosage
  • Clopidogrel* / adverse effects
  • Clopidogrel* / therapeutic use
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy
  • Drug Interactions*
  • Drug-Eluting Stents
  • Dual Anti-Platelet Therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / mortality
  • Platelet Aggregation Inhibitors* / administration & dosage
  • Platelet Aggregation Inhibitors* / adverse effects
  • Platelet Aggregation Inhibitors* / pharmacology
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Platelet Function Tests*
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • Receptors, Purinergic P2Y12 / blood
  • Receptors, Purinergic P2Y12 / drug effects
  • Registries*
  • Republic of Korea
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Clopidogrel
  • Platelet Aggregation Inhibitors
  • Calcium Channel Blockers
  • Receptors, Purinergic P2Y12
  • Purinergic P2Y Receptor Antagonists
  • P2RY12 protein, human

Associated data

  • ClinicalTrials.gov/NCT04734028