The art of delivering evidence-based dual antiplatelet therapy

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Applied Evidence

The art of delivering evidence-based dual antiplatelet therapy

J Fam Pract. 2018 December;67(12):758-766

By

William J. Curry, MD, MS

Charles E. Chambers, MD

Gwendolyn W. Curry, MD

Elizabeth W. Curry, MD

This review, which details 2 DAPT risk scoring systems and includes a treatment guide, can help ensure that you deliver the right treatment to the right patients.

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PRACTICE RECOMMENDATIONS

› Use a dual antiplatelet therapy (DAPT) risk calculator to encourage patient-centric decisions when presenting information to the health care team and the patient. B

› Consider the potential benefit of a shorter duration of DAPT for patients who 1) have prior bleeding complications or 2) are taking an oral anticoagulant, chronic corticosteroid, or nonsteroidal anti-inflammatory drug. B

› Continue aspirin use upon completion of DAPT or if a P2Y12 inhibitor is being held for surgery. A

› Reduce the risk of recurrent stroke in patients who have had a mild ischemic stroke or transient ischemic attack by providing DAPT for 21 to 28 days, followed by aspirin indefinitely—so long as treatment can begin within 24 hours of the event. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

References

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11. Wenaweser P, Dörffler-Melly J, Imboden K, et al. Stent thrombosis is associated with an impaired response to antiplatelet therapy. J Am Coll Cardiol. 2005;45:1748-1752.

12. Farid NA, Kurihara A, Wrighton SA. Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. J Clin Pharmacol. 2010;50:126-142.

13. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Euro Heart J. 2017;39:213-260.

14. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. J Am Coll Cardiol. 2016;68:1082-1115.

15. Jernberg T, Payne CD, Winters KJ, et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J. 2006;27:1166-1173.

16. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001-2015.

17. Debesh PP, Oestreich JH. Ticagrelor: pharmacokinetics, pharmacodynamics, clinical efficacy, and safety. Pharmacotherapy. 2014;34:1077-1090.

18. Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease. Circulation. 2014;130:1749-1767.

19. Benedetto U, Altman DG, Gerry S, et al. Impact of dual antiplatelet therapy after coronary artery bypass surgery on 1-year outcomes in the Arterial Revascularization Trial. Eur J Cardiothorac Surg. 2017;52:456-461.

20. Toyota T, Shiomi H, Morimoto T, et al. Short versus prolonged dual antiplatelet therapy (DAPT) duration after coronary stent implantation: a comparison between the DAPT study and 9 other trials evaluating DAPT duration. PLoS One. 2017;12:e0174502.

21. Costa F, van Klaveren D, James S, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017;389:1025-1034.

22. PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy (PRECISE-DAPT) WebCalculator. www.precisedaptscore.com/predapt/webcalculator.html. Accessed October 21, 2018.

23. Yeh RW, Secemsky EA, Kereiakes DJ, et al; DAPT Study Investigators. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016;315:1735-1749.

24. American College of Cardiology. DAPT Risk Calculator. http://tools.acc.org/DAPTriskapp/#!/content/calculator/. Accessed October 21, 2018.

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26. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377:1513-1524.

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29. Fleisher LA, Fleischmann KE, Auerbach AD, et al; American College of Cardiology; American Heart Association. 2014 ACC/AHA Guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;64:e77-e137.

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31. Wong KS, Chen C, Fu J, et al; CLAIR study investigators. Clopidogrel plus aspirin versus aspirin alone for reducing embolisation in patients with acute symptomatic cerebral or carotid artery stenosis (CLAIR study): a randomised, open-label, blinded-endpoint trial. Lancet Neurol. 2010:9:489-497.

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33. Diener HC, Bogousslavsky J, Brass LM, et al; MATCH investigators. Aspirin and clopidogrel compared to clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:331-337.

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In landmark clinical research published in 1996, aspirin (ASA) and the P2Y12 inhibitor ticlopidine used after coronary artery stent implantation was compared to intravenous anticoagulation—at the time, the postprocedure standard of care for preventing thrombosis. What investigators found was a marked reduction in cardiac and hemorrhagic events in patients who were treated with this novel dual antiplatelet therapy (DAPT).¹ Since publication of the results of that trial, the use of ASA plus a P2Y12 inhibitor has expanded to treating acute coronary syndrome (ACS) and stroke.

Over the past 2 decades, much research has been devoted to 1) determining the effectiveness of more potent P2Y12 inhibitors—which block chemoreceptors for adenosine diphosphate—to prevent stent thrombosis and 2) safer regimens to reduce hemorrhagic complications.

When does stent thrombosis occur?

The timing of stent thrombosis is defined as:

acute (within 24 hours of placement),
subacute (within 30 days),
late (within 1 year), or
very late (after 1 year).

Acute stent thrombosis is almost always related to technical issues surrounding stent implantation. Subacute thrombosis is almost always platelet activation within the stent with thrombus formation—the reason why antiplatelet therapy is beneficial and anticoagulation pathway inhibition is not beneficial.

The delay in healing caused by drug-eluting stents makes it necessary to administer dual antiplatelet therapy for a longer duration—an increase not needed with bare-metal stents.

Late stent complications can be caused by thrombosis, but also might be related to restenosis by 4 to 6 months—ie, tissue overgrowth as the stent becomes part of the body, not clot formation. In several studies, restenosis was a significant issue with balloon dilation alone, occurring in 33% of patients.² Bare-metal stents (BMS) have been shown to reduce the rate of restenosis to approximately 20%; drug-eluting stents (DES) have further decreased restenosis to approximately 5%, in various reports, by impairing endothelial healing, thus limiting tissue overgrowth that leads to restenosis.³ This delay in healing caused by DES makes it necessary to administer DAPT for a longer duration—an increase that is not needed with BMS.

^{© Myriam and Steve Oh}

DAPT has well-defined benefits

As drug-eluting stents were introduced and improved, trials studying optimal duration of DAPT showed that longer duration of treatment reduced stroke incidence and the long-term risk of myocardial infarction (MI) unrelated to stent thrombosis.⁴ Nuances in the treatment of ischemic coronary artery disease (CAD) and secondary prevention of stroke can be perplexing, as can be P2Y12inhibitor selection. Here, we review DAPT agents and discuss current evidence and evidence-based guidelines, thus providing a framework to better understand treatment options and recommendations.

What constitutes DAPT?

Many combinations of antiplatelet therapy are possible but, in the United States, DAPT denotes ASA 81 mg/d plus any of the 3 P2Y12inhibitors: clopidogrel, prasugrel, and ticagrelor. Stimulation of the platelet P2Y12receptor causes stimulation of the platelet glycoprotein IIb/IIIa receptor, which, in turn, enhances platelet degranulation, thromboxane production, and prolonged platelet aggregation. Blocking P2Y12receptors thus impairs the thrombotic processes.⁵

Continue to: ASA, as a component of DAPT...