Fixed-dose combinations of antiplatelet drugs


Authors: R. Miklík;  M. Pavlušová
Authors‘ workplace: Interní kardiologická klinika LF MU a FN Brno
Published in: Kardiol Rev Int Med 2016, 18(2): 109-114

Overview

Fixed-dose combinations of several active substances in one tablet provide advantages in the treatment of diabetes, hypertension and chronic pain. This issue is much more challenging when considering drug combinations that interfere with haemostasis. Indications of antiplatelet drugs vary depending on the duration of therapy required, the degree of aggressiveness of treatment and on the presence of numerous modifying factors influencing drug effectiveness. Combinations of these drugs increase the risk of major bleeding complications. Two fixed-dose antiplatelet pharmaceutical products are currently available: aspirin + dipyridamole and aspirin + clopidogrel. This article discusses the benefits and pitfalls of these combinations and provides an overview and comparison of other antiaggregation drugs and their potential for fixed-dose preparations in the future.

Keywords:
antiplatelet therapy –  fixed-dose combination –  aspirin resistance –  P2Y12 receptor blockers


Sources

1. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326: 1419. doi: 10.1136/ bmj.326.7404.1419.

2. Gautam CS, Saha L. Fixed dose drug combinations (FDCs): rational or irrational: a view point. Br J Clin Pharmacol 2008; 65: 795– 796. doi: 10.1111/ j.1365-2125.2007.03089.x.

3. Becerra V, Gracia A, Desai K et al. Cost-effectiveness and public health benefit of secondary cardiovascular disease prevention from improved adherence using a polypill in the UK. BMJ Open 2015; 5: e007111. doi: 10.1136/ bmjopen-2014-007111.

4. Bangalore S, Kamalakkannan G, Parkar S et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007; 120: 713– 719. doi: 10.1016/ j.amjmed.2006.08.033.

5. Mathews R, Wang TY, Honeycutt E et al. Persistence with secondary prevention medications after acute myocardial infarction: insights from the TRANSLATE-ACS study. Am Heart J 2015; 170: 62– 69. doi: 10.1016/ j.ahj.2015.03.019.

6. AGGRENOX, POR CPS RDR 60X25MG/ 200MG. Státní ústav pro kontrolu léčiv. Dostupné z: http:/ / www.sukl.cz/ modules/ medication/ detail.php?kod=0057364&tab=texts.

7. European Stroke Organisation (ESO) Executive Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25: 457– 507. doi: 10.1159/ 000131083.

8. Halkes PH, van Gijn J, Kappelle LJ et al. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 2006; 367: 1665– 1673. doi: 10.1016/ S0140-6736(06)68734-5.

9. Diener HC, Cunha L, Forbes C et al. European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996; 143: 1– 13. doi: 10.1016/ S0022-510X(96)00308-5.

10. Diener HC, Sacco RL, Yusuf S et al. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-control­led study. Lancet Neurol 2008; 7: 875– 884. doi: 10.1016/ S1474-4422(08)70198-4.

11. Duoplavin SPC. Dostupné z: http:/ / www.ema.europa.eu/ docs/ cs_CZ/ document_library/ EPAR-Product_Information/ human/ 001143/ WC500087025.pdf.

12. Baigent C, Blackwell L, Collins R et al. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849– 1860. doi: 10.1016/ S0140-6736(09)60503-1.

13. Tournoij E, Peters RJ, Langenberg M et al. The prevalence of intolerance for low-dose acetylsalicyl­acid in the secondary prevention of atherothrombosis. Eur J Vasc Endovasc Surg 2009; 37: 597– 603. doi: 10.1016/ j.ejvs.2009.01.009.

14. Tendera M, Aboyans V, Bartelink ML et al. ESC Guide­lines on the dia­gnosis and treatment of peripheral artery diseases. Eur Heart J 2011; 32: 2851– 2906. doi: 10.1093/ eurheartj/ ehr211.

15. Wang ZY, Chen M, Zhu LL et al. Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination ther­apy. Ther Clin Risk Manag 2015; 11: 449– 467. doi: 10.2147/ TCRM.S80437.

16. Campbell CL, Steinhubl SR. Variability in response to aspirin: do we understand the clinical relevance? J Thromb Haemost 2005; 3: 665– 669. doi: 10.1111/ j.1538-7836.2005.01119.x.

17. Eikelboom JW, Hankey GJ. Failure of aspirin to prevent atherothrombosis: potential mechanisms and implications for clinical practice. Am J Cardiovasc Drugs 2004; 4: 57– 67.

18. Hankey GJ, Eikelboom JW. Aspirin resistance. Lancet 2006; 367: 606– 617. doi: 10.1016/  S0140-6736(06)68040-9.

19. Carney RM, Freedland KE, Eisen SA et al. Adherence to a prophylactic medication regimen in patients with symp­tomatic versus asymp­tomatic ischemic heart disease. Behav Med 1998; 24: 35– 39. doi: 10.1080/ 08964289809596379.

20. Larsen SB, Grove EL, Neergaard-Petersen S et al. Determinants of reduced antiplatelet effect of aspirin in patients with stable coronary artery disease. PloS One 2015; 10: e0126767. doi: 10.1371/ journal.pone.0126767.

21. Gum PA, Kottke-Marchant K, Welsh PA et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961– 965. doi: 10.1016/ S0735-1097(02)03014-0.

22. Součková L, Opatřilová R, Suk P et al. Impaired bio­availability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR). Eur J Clin Pharmacol 2013; 69: 309– 317. doi: 10.1007/ s00228-012-1360-0.

23. Osmancik P, Jirmar R, Hulikova K et al. A comparison of the VASP index between patients with hemodynamically complicated and uncomplicated acute myocardial infarction. Catheter Cardiovasc Interv 2010; 75: 158– 166. doi: 10.1002/ ccd.22248.

24. Motovska Z, Ondrakova M, Doktorova M et al. Severe left ventricular systolic dysfunction is independently associated with high on-clopidogrel platelet reactivity. Am J Cardiovasc Drugs 2014; 14: 313– 318. doi: 10.1007/ s40256-014-0074-3.

25. Angiolillo DJ, Fernández-Ortiz A, Bernardo E et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability. Eur Heart J 2004; 25: 1903– 1910. doi: 10.1016/ j.ehj.2004.07.036.

26. Patti G, Colonna G, Pasceri V et al. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study. Circulation 2005; 111: 2099– 2106. doi: 10.1161/ 01.CIR.0000161383.06692.D4.

27. Mega JL, Close SL, Wiviott SD et al. Cyto­chrome P450 genetic polymorphisms and the response to prasugrel relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 2009; 119: 2553– 2560. doi: 10.1161/ CIRCULATIONAHA.109.851949.

28. Aradi D, Storey RF, Komócsi A et al. Expert position paper on the role of platelet function test­ing in patients undergoing percutaneous coronary intervention. Eur Heart J 2014; 35: 209– 215. doi: 10.1093/ eurheartj/ eht375.

29. Bonaca MP, Bhatt DL, Cohen M et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372: 1791– 1800. doi: 10.1056/ NEJMoa1500857.

30. Mauri L, Kereiakes DJ, Yeh RW et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014; 371: 2155– 2166. doi: 10.1056/ NEJMoa1409312.

31. Udell JA, Bonaca MP, Collet JP et al. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J 2016; 37: 390– 399. doi: 10.1093/ eurheartj/ ehv443.

32. Wiley B, Fuster V. The concept of the polypill in the prevention of cardiovascular disease. Ann Glob Health 2014; 80: 24– 34. doi: 10.1016/ j.aogh.2013.12.008.

Labels
Paediatric cardiology Internal medicine Cardiac surgery Cardiology
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account