Comparison of dual antiplatelet therapy prescribed as one-pill versus two-pill regimen

Summary

Fixed-dose combination (FDC) drugs can simplify the medication regimen and potentially improve adherence. However, evidence is lacking about the efficacy and safety of FDC drugs of clopidogrel plus aspirin. Individual data from the three independent MR-CAPCIS trials were pooled and analysed. In those trials, subjects who had been treated with either dual antiplatelet therapy (DAPT) or aspirin alone after drug-eluting stent (DES) implantation were randomly assigned to one-pill or to two-pill DAPT group. Platelet reactivity was measured with VerifyNow-P2Y12 and aspirin point-of-care assays at baseline and eight weeks after treatment. In the present study, primary efficacy endpoint was changes in platelet reactivity unit (PRU) between baseline and eight weeks. A total of 965 subjects were analysed. In prior clopidogrel and aspirin users, PRU was well maintained regardless of switching to either one-pill or two-pill DAPT (ΔPRU=0.4 vs 0.0, p=0.939). In prior aspirin users, PRU was decreased by 73.7 in one-pill DAPT and 77.5 in two-pill DAPT group, with no differences between them (p=0.499). The incidence of high on-treatment platelet reactivity at eight weeks, defined as PRU≥235 in Western people, was 34.8 % in one-pill DAPT group and 37.6 % in two-pill DAPT group (p=0.380), and that defined as PRU ≥275 in Oriental people was 17.7 vs 21.7 % (p=0.129). Independent predictors of high platelet reactivity on clopidogrel were female gender, increasing age, and diabetes. Study drugs were well tolerated. In conclusion, FDC one-pill DAPT showed similar efficacy to two-pill DAPT in terms of platelet reactivity in patients receiving DES in Korea.

Keywords

Aspirin - clopidogrel - dual antiplatelet therapy - fixed-dose combination

^* The first two authors contributed equally to this work.

• References

• 1 Garg S, Serruys PW. Coronary stents: current status. J Am Coll Cardiol 2010; 56 (10) S1-42.
• 2 Kang SH, Park KW, Kang DY. et al. Biodegradable-polymer drug-eluting stents vs bare metal stents vs durable-polymer drug-eluting stents: a systematic review and Bayesian approach network meta-analysis. Eur Heart J 2014; 35: 1147-1158.
• 3 Levine GN, Bates ER, Blankenship JC. et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011; 124: 2574-2609.
• 4 Authors/Task Force. Windecker S, Kolh P. et al. 2014 ESC/EACTS Guidelines on myocardial revascularisation: The Task Force on Myocardial Revascularisation of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35: 2541-2619.
• 5 Grines CL, Bonow RO, Casey Jr. DE. et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007; 115: 813-818.
• 6 Panjabi S, Lacey M, Bancroft T. et al. Treatment adherence, clinical outcomes, and economics of triple-drug therapy in hypertensive patients. J Am Soc Hypertens 2013; 07: 46-60.
• 7 Thygesen K, Alpert JS, Jaffe AS. et al. Third universal definition of myocardial infarction. Circulation 2012; 126: 2020-2035.
• 8 Price MJ, Endemann S, Gollapudi RR. et al. Prognostic significance of postclopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 2008; 29: 992-1000.
• 9 Marcucci R, Gori AM, Paniccia R. et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a pointof-care assay: a 12-month follow-up. Circulation 2009; 119: 237-242.
• 10 Park KW, Jeon KH, Kang SH. et al. Clinical outcomes of high on-treatment platelet reactivity in Koreans receiving elective percutaneous coronary intervention (from results of the CROSS VERIFY study). Am J Cardiol 2011; 108: 1556-1563.
• 11 Collet JP, Cuisset T, Range G. et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367: 2100-2109.
• 12 Nielsen HL, Kristensen SD, Thygesen SS. et al. Aspirin response evaluated by the VerifyNow Aspirin System and light transmission aggregometry. Thrombosis Res 2008; 123: 267-273.
• 13 Bangalore S, Kamalakkannan G, Parkar S. et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 2007; 120: 713-719.
• 14 Castellano JM, Sanz G, Penalvo JL. et al. A polypill strategy to improve adherence: results from FOCUS (Fixed-dose Combination Drug for Secondary Cardiovascular Prevention) Project. J Am Coll Cardiol 2014; 64: 2071-2082.
• 15 Pocock SJ, Abdalla M. The hope and the hazards of using compliance data in randomized controlled trials. Stat Med 1998; 17: 303-317.
• 16 Brar SS, ten Berg J, Marcucci R. et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol 2011; 58: 1945-1954.
• 17 Aradi D, Komocsi A, Price MJ. et al. Efficacy and safety of intensified antiplatelet therapy on the basis of platelet reactivity testing in patients after percutaneous coronary intervention: systematic review and meta-analysis. Intern J Cardiol 2013; 167: 2140-2148.
• 18 Bonello L, Tantry US, Marcucci R. et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56: 919-933.
• 19 Ko YG, Suh JW, Kim BH. et al. Comparison of 2 point-of-care platelet function tests, VerifyNow Assay and Multiple Electrode Platelet Aggregometry, for predicting early clinical outcomes in patients undergoing percutaneous coronary intervention. Am Heart J 2011; 161: 383-390.
• 20 Campo G, Parrinello G, Ferraresi P. et al. Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol 2011; 57: 2474-2483.
• 21 Cattaneo M. New P2Y(12) inhibitors. Circulation 2010; 121: 171-179.
• 22 Park KW, Park JJ, Jeon KH. et al. Clinical predictors of high posttreatment platelet reactivity to clopidogrel in Koreans. Cardiovasc Therapeutics 2012; 30: 5-11.