dual antiplatelet therapy (DAPT)
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Pharmacology
- therapy with two antiplatelet agents generally clopidogrel & aspirin
- low-dose aspirin (75-100 mg/day) in all regimens[11]
- it seems persantine & aspirin would also qualify, though these two agents are less commonly associated with the term DPAT
- ticagrelor may be preferred to clopidogrel after acute coronary syndrome without stent[11] Adverse events:
- risk of hemorrhage* (resulting in emergency department visit) associated with dual antiplatelet therapy is less than that for warfarin (3.7 vs 1.2 per 1000 outpatient prescription visits)
- nuisance bleeding is common during the first year after MI, & adversely affects quality of life[2]
- DAPT for > 12 months associated with higher rate of bleeding- related mortality (RR=0.1.5), but lower rate of myocardial infarction (RR=0.75) than DAPT for < 12 months[14]
- all-cause mortality also higher with > 12 months DAPT (RR=1.2)
- long-term DAPT (> 12 months) associated with decreased risks for myocardial infarction & stent thrombosis but increased risks for noncardiac death &major bleeding relative to short-term DAPT (< 6 months)[19]
- 1-3 months of dual anti-platelet therapy sufficient after PCI with drug-eluting coronary stent[18]
- dual antiplatelet therapy increases risk of systemic bleeding after ischemic stroke ~5-6 events per 100 patient-years relative to monotherapy[15], but may not increase risk of intracerebral hemorrhage[15]
* proton pump inhibitor provides protection from GI bleeding without affecting adverse cardiovascular risk[11]
Indications
- following coronary stent (one year of therapy)
- 6-12 months for drug-eluting stent[11]
- > 1 month for bare metal stent
- following acute coronary syndrome or MI (STEMI, NSTEMI)
- patients with stable CAD undergoing CABG
- 12 months of therapy
Contraindications
- secondary prevention of cardiovascular events[6]
- patients with diabetes mellitus & coronary artery disease[20]
- chronic stable angina in the absence of revascularization[21]
Benefit/risk
- for 1 year following coronary stent
- no mortality benefit[5]
- number needed to treat (NNT) to prevent 1 non-fatal MI or 1 stroke = 27[5]
- number need to harm (major hemorrhage) = 117
- no benefit for secondary prevention of cardiovascular events[6]
- reduces risk of new stroke after TIA or ischemic stroke at cost of increased risk of bleeding vs aspirin alone[22]
Management
- duration of therapy is usually 6-12 months[10]
- 12 months of dual antiplatelet therapy after PCI with drug- eluting stent is the standard of care[7]
- 3-6 months of dual antiplatelet therapy is associated with less bleeding but no difference in ischemia or thrombosis relative to 12 months of therapy[7]
- > 6 months of dual antiplatelet therapy is associated with fewer MIs but more bleeding & more deaths relative to < 6 months of therapy, but absolute risk is low (0.03% for MI)[8]*
- 12 months of therapy does not decrease risk of myocardial infarction, cardiac death or stent thrombosis & increases risk of bleeding relative to 6 months of therapy with or without type 2 diabetes[13]
- 6 months of DAPT after drug-eluting stent for STEMI non-inferior to 12 months of DAPT[16]
- mortality benefit for prolonged dual antiplatelet therapy is unlikely[3]
- Dual Antiplatelet therapy score (DAPT score) may predict patients that might benefit from prolonged dual antiplatelet therapy
- elective non-cardiac surgery should be delayed at least 30 days after bare metal stent implantion & 6 months after drug-eluting stent implantation (i.e. after DAPT is complete)[11]
* calculator to predict risks of ischemic events vs bleeding for continued DAPT therapy beyond 1 year after coronary stent placement[9]
More general terms
Additional terms
References
- ↑ Shehab N et al National Estimates of Emergency Department Visits for Hemorrhage-Related Adverse Events From Clopidogrel Plus Aspirin and From Warfarin Arch Intern Med. 2010;170(21):1926-1933 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21098354 <Internet> http://archinte.ama-assn.org/cgi/content/abstract/170/21/1926
- ↑ 2.0 2.1 Amin AP et al. Nuisance bleeding with prolonged dual antiplatelet therapy after acute myocardial infarction and its impact on health status. J Am Coll Cardiol 2013 May 28; 61:2130 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23541975
Dauerman HL. The softer side of bleeding. J Am Coll Cardiol 2013 May 28; 61:2139. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23541969 - ↑ 3.0 3.1 Brett AS The Pros and Cons of Dual Antiplatelet Therapy. NEJM Journal Watch. Feb 26, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
Mauri L et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014 Dec 4; 371:2155. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25399658 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1409312
Colombo A and Chieffo A. Dual antiplatelet therapy after drug-eluting stents - How long to treat? N Engl J Med 2014 Dec 4; 371:2225. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25399657 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1413297
Gilard M et al. Six-month versus 24-month dual antiplatelet therapy after implantation of drug eluting stents in patients non-resistant to aspirin: ITALIC, a randomized multicenter trial. J Am Coll Cardiol. 2014 Nov 16. pii: S0735-1097(14)06970-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25461690
Gilard M et al. 6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: The randomized, multicenter ITALIC trial. J Am Coll Cardiol 2015 Mar 3; 65:777. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25461690 <Internet> http://www.sciencedirect.com/science/article/pii/S0735109714069708
Elmariah S et al. Extended duration dual antiplatelet therapy and mortality: A systematic review and meta-analysis. Lancet 2014 Nov 16 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25467565 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962052-3/abstract - ↑ Bonaca MP et al Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. N Engl J Med. March 14, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25773268 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1500857
Keaney JF Jr Balancing the Risks and Benefits of Dual Platelet Inhibition. N Engl J Med. March 14, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25773507 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1502137 - ↑ 5.0 5.1 5.2 The NNT: Clopidogrel Added To Aspirin During and After a Coronary Event or a Stent Procedure. http://www.thennt.com/nnt/clopidogrel-added-to-aspirin-during-and-after-a-coronary-event-or-stenting/
- ↑ 6.0 6.1 6.2 The NNT: Clopidogrel Added to Aspirin to Prevent a Second Heart Attack Or Stroke. http://www.thennt.com/nnt/clopidogrel-with-aspirin-for-prevention-after-prior-heart-attack-or-stroke/
Squizzato A, Keller T, Romualdi E, Middeldorp S Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD005158 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21249668
Bowry AD, Brookhart MA, Choudhry NK. Meta-analysis of the efficacy and safety of clopidogrel plus aspirin as compared to antiplatelet monotherapy for the prevention of vascular events. Am J Cardiol. 2008 Apr 1;101(7):960-6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18359315 - ↑ 7.0 7.1 7.2 Navarese EP et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: Meta-analysis of randomised controlled trials. BMJ 2015 Apr 16; 350:h1618. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25883067 <Internet> http://www.bmj.com/content/350/bmj.h1618
- ↑ 8.0 8.1 Spencer FA et al Longer Versus Shorter Duration Dual-Antiplatelet Therapy After Drug-Eluting Stent Placement: A Systematic Review and Meta- analysis. Ann Intern Med. May 26, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26005909 <Internet> http://annals.org/article.aspx?articleid=2297227
- ↑ 9.0 9.1 Yeh RW, Secemsky E, Kereiakes DJ Individualizing Treatment Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: An Analysis of the DAPT Study. American Heart Association. 2015 Annual Meeting. Nov 10. http://www.abstractsonline.com/pp8/#!/3795/presentation/47453
DAPT Score Calculator http://www.daptstudy.org/for-clinicians/score_calculator.htm - ↑ 10.0 10.1 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: A Report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/ AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. March 29, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27026020 <Internet> http://circ.ahajournals.org/content/early/2016/03/28/CIR.0000000000000404.full.pdf+html
Yeh RW, Secemsky EA, Kereiakes DJ et al Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA. Published online March 29, 2016. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27022822 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2508253 - ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 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: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Sep 6;68(10):1082-115 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27036918 Free full text
- ↑ Vaduganathan M et al. Proton-pump inhibitors reduce gastrointestinal events regardless of aspirin dose in patients requiring dual antiplatelet therapy. J Am Coll Cardiol 2016 Mar 16 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27012778
- ↑ 13.0 13.1 Gargiulo G, Windecker S, da Costa BR et al Short term versus long term dual antiplatelet therapy after implantation of drug eluting stent in patients with or without diabetes: systematic review and meta-analysis of individual participant data from randomised trials. BMJ 2016;355:i5483 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27811064 Free full text <Internet> http://www.bmj.com/content/355/bmj.i5483
Ball J Optimal duration of dual antiplatelet therapy after stent implantation in patients with or without diabetes. BMJ 2016;355:i5730 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27811234 <Internet> http://www.bmj.com/content/355/bmj.i5730 - ↑ 14.0 14.1 Palmerini T, Bacchi Reggiani L et al. Bleeding-related deaths in relation to the duration of dual- antiplatelet therapy after coronary stenting. J Am Coll Cardiol 2017 Apr 25; 69:2011. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28427576 <Internet> http://www.sciencedirect.com/science/article/pii/S0735109717306964
Rao SV, Harrington RA. Bleeding and mortality with dual antiplatelet therapy: The Rashomon effect. J Am Coll Cardiol 2017 Apr 25; 69:2023. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28427577 <Internet> http://www.sciencedirect.com/science/article/pii/S0735109717360187 - ↑ 15.0 15.1 15.2 Hilkens NA, Algra A, Kappelle LJ, et al. Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke. Neurology 2018 Feb 20; 90:e683 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29374102 Free PMC Article <Internet> http://n.neurology.org/content/90/8/e683
- ↑ 16.0 16.1 Kedhi E, Fabris E, van der Ent M et al Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial. BMJ 2018;363:k3793 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30279197 Free Article https://www.bmj.com/content/363/bmj.k3793
- ↑ 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: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Thorac Cardiovasc Surg. 2016 Nov;152(5):1243-1275. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27751237
- ↑ 18.0 18.1 Watanabe H, Domei R, Morimoto T et al Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial. JAMA. 2019;321(24):2414-2427. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31237644 https://jamanetwork.com/journals/jama/fullarticle/2736563
Hahn JH, Song YB, Oh JH et al Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention. The SMART-CHOICE Randomized Clinical Trial. JAMA. 2019;321(24):2428-2437 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31237645 https://jamanetwork.com/journals/jama/fullarticle/2736564
Ziada KM, Moliterno DJ. Dual Antiplatelet TherapyIs It Time to Cut the Cord With Aspirin? JAMA. 2019;321(24):2409-2411 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31237621 https://jamanetwork.com/journals/jama/fullarticle/2736537 - ↑ 19.0 19.1 Yin SHL, Xu P, Wang B et al Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent: systematic review and network meta-analysis. BMJ 2019;365:l2222 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31253632 Free Article https://www.bmj.com/content/365/bmj.l2222
- ↑ 20.0 20.1 Steg PG, Bhatt DL, Simon T et al. Ticagrelor in patients with stable coronary disease and diabetes. N Engl J Med 2019 Sep 1; PMID: https://www.ncbi.nlm.nih.gov/pubmed/31475798 https://www.nejm.org/doi/10.1056/NEJMoa1908077
- ↑ 21.0 21.1 Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
- ↑ 22.0 22.1 Gao Y, Chen W, Pan Y, et al. Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke. N Engl J Med. 2023 Dec 28;389(26):2413-2424. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38157499 https://www.nejm.org/doi/10.1056/NEJMoa2309137