Top

Published in:

01-03-2021 | Gastrointestinal Bleeding | Original Article

Comparison of effects of triple antithrombotic therapy and dual antiplatelet therapy on long-term outcomes of acute myocardial infarction

Authors: Mei-Tzu Wang, Cheng Chung Hung, Kun-Chang Lin, Guang-Yuan Mar, Shu-Hung Kuo, Cheng-Hung Chiang, Chin-Chang Cheng, Feng-You Kuo, Hsing-Li Liang, Wei-Chun Huang

Published in: Heart and Vessels | Issue 3/2021

Abstract

Warfarin is an alternate choice for patients who are not eligible for non-vitamin K oral anticoagulants after acute myocardial infarction (AMI). This study aimed to compare the long-term outcome of triple antithrombotic therapy (TAT) with that of dual antiplatelet therapy (DAPT) after AMI. This was a nationwide, propensity score-matched, case–control study of 186,112 first AMI patients, of whom 2,825 received TAT comprising aspirin, clopidogrel, and warfarin. Propensity score matching in a ratio of 1:4 by age, sex, comorbidities, and treatment was adopted, Finally, 2,813 AMI patients and 11,252 matched controls that were administered TAT and DAPT (aspirin and clopidogrel), respectively, were included in our analysis. The 12-year overall survival rate did not differ between both strategies (P = .3167). TAT was beneficial in old age (hazard ratio [HR] = 0.92), female sex (HR = 0.86), atrial fibrillation (AF) (HR = 0.80), hypertension (HR = 0.92), cerebrovascular accident (HR = 0.90), and in the absence of percutaneous coronary intervention (HR = 0.79). TAT reduced the rate of recurrent myocardial infarction (P = .0108) but did not affect the rate of stroke (P = .4867), gastrointestinal bleeding (P = .3889), or intracranial hemorrhage (ICH) (P = .3449). TAT reduces the incidence of recurrent myocardial infarction and does not increase the risk of major bleeding, while compared to DAPT.

Available only for authorised users

Montalescot G (2000) Value of antiplatelet therapy in preventing thrombotic events in generalized vascular disease. Clin Cardiol 23(Suppl 6):18–22

Ho WK, Hankey GJ, Eikelboom JW (2004) Prevention of coronary heart disease with aspirin and clopidogrel: efficacy, safety, costs and cost-effectiveness. Expert Opin Pharmacother 5:493–503PubMed

Faxon DP, Nesto RW (2006) Antiplatelet therapy in populations at high risk of atherothrombosis. J Natl Med Assoc 98:711–721PubMedPubMedCentral

American College of Emergency P, Society for Cardiovascular A, Interventions, O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX, Anderson JL, Jacobs AK, Halperin JL, Albert NM, Brindis RG, Creager MA, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Kushner FG, Ohman EM, Stevenson WG, Yancy CW (2013) 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 61:e78–140

Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimsky P (2018) 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 39:119–177PubMed

Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S, Baumgartner H, Gaemperli O, Achenbach S, Agewall S, Badimon L, Baigent C, Bueno H, Bugiardini R, Carerj S, Casselman F, Cuisset T, Erol C, Fitzsimons D, Halle M, Hamm C, Hildick-Smith D, Huber K, Iliodromitis E, James S, Lewis BS, Lip GY, Piepoli MF, Richter D, Rosemann T, Sechtem U, Steg PG, Vrints C, Luis Zamorano J, Management of Acute Coronary Syndromes in Patients Presenting without Persistent STSEotESoC (2016) 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European society of cardiology (ESC). Eur Heart J 37:267–315PubMed

Moulson N, LaHaye SA, Bertrand OF, MacHaalany J (2017) Prophylactic warfarin post anterior ST-elevation myocardial infarction: a systematic review and meta-analysis. Cardiovasc Revasc Med 18:559–564PubMed

Hess CN, Peterson ED, Peng SA, de Lemos JA, Fosbol EL, Thomas L, Bhatt DL, Saucedo JF, Wang TY (2015) Use and outcomes of triple therapy among older patients with acute myocardial infarction and atrial fibrillation. J Am Coll Cardiol 66:616–627PubMed

Bavishi C, Koulova A, Bangalore S, Sawant A, Chatterjee S, Ather S, Valencia J, Sarafoff N, Rubboli A, Airaksinen JK, Lip GY, Tamis-Holland JE (2016) Evaluation of the efficacy and safety of dual antiplatelet therapy with or without warfarin in patients with a clinical indication for DAPT and chronic anticoagulation: a meta-analysis of observational studies. Catheter Cardiovasc Interv 88:E12–22PubMed

10.

Kuo PL, Lin KC, Tang PL, Cheng CC, Huang WC, Chiang CH, Lin HC, Chuang TJ, Wann SR, Mar GY, Cheng JS, Liu CP (2016) Contribution of hepatitis B to long-term outcome among patients with acute myocardial infarction: a nationwide study. Medicine (Baltimore) 95:e2678

11.

Wang MT, Lin SC, Tang PL, Hung WT, Cheng CC, Yang JS, Chang HT, Liu CP, Mar GY, Huang WC (2017) The impact of DPP-4 inhibitors on long-term survival among diabetic patients after first acute myocardial infarction. Cardiovasc Diabetol 16:89PubMedPubMedCentral

12.

Wang MT, Liang HL, Hung CC, Tang PL, Lin KC, Chiang CH, Kuo FY, Yang JS, Liu CP, Mar GY, Huang WC (2019) Combination therapy with dipyridamole and clopidogrel for secondary stroke prevention in aspirin-intolerant patients after myocardial infarction: results of a nationwide case-control study. CNS Drugs 33:175–185PubMedPubMedCentral

13.

Liu ES, Chiang CH, Hung WT, Tang PL, Hung CC, Kuo SH, Liu CP, Chen YS, Mar GY, Huang WC (2019) Comparison of long-term mortality in patients with acute myocardial infarction associated with or without sepsis. Int J Infect Dis 79:169–178PubMed

14.

Wang MT, Tsai CK, Kuo SH, Huang WC, Lin KC, Hung WT, Cheng CC, Tang PL, Hung CC, Yang JS, Liang HL, Mar GY, Liu CP (2018) The dipyridamole added to dual antiplatelet therapy in cerebral infarction after first acute myocardial infarction: a nationwide Case-Control Study. Front Neurol 9:1003PubMedPubMedCentral

15.

Kuo SH, Hung WT, Tang PL, Huang WC, Yang JS, Lin HC, Mar GY, Chang HT, Liu CP (2018) Impact of hepatitis C virus infection on long-term mortality after acute myocardial infarction: a nationwide population-based, propensity-matched cohort study in Taiwan. BMJ Open 8:e017412PubMedPubMedCentral

16.

Hsieh CY, Su CC, Shao SC, Sung SF, Lin SJ, Kao Yang YH, Lai EC (2019) Taiwan's National Health Insurance Research Database: past and future. Clin Epidemiol 11:349–358PubMedPubMedCentral

17.

Cheng CL, Lee CH, Chen PS, Li YH, Lin SJ, Yang YH (2014) Validation of acute myocardial infarction cases in the national health insurance research database in taiwan. J Epidemiol 24:500–507PubMedPubMedCentral

18.

Cheng CL, Chien HC, Lee CH, Lin SJ, Yang YH (2015) Validity of in-hospital mortality data among patients with acute myocardial infarction or stroke in National Health Insurance Research Database in Taiwan. Int J Cardiol 201:96–101PubMed

19.

Schulman S, Kearon C (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3:692–694PubMed

20.

Kang EY, Lien R, Wang NK, Lai CC, Chen KJ, Hwang YS, Lin CM, Wu WC, Hsu KH (2018) Retinopathy of prematurity trends in Taiwan: a 10-year nationwide population study. Invest Ophthalmol Vis Sci 59:3599–3607PubMed

21.

Konstantino Y, Iakobishvili Z, Porter A, Sandach A, Zahger D, Hod H, Hammerman H, Gottlieb S, Behar S, Hasdai D (2006) Aspirin, warfarin and a thienopyridine for acute coronary syndromes. Cardiology 105:80–85PubMed

22.

Hermosillo AJ, Spinler SA (2008) Aspirin, clopidogrel, and warfarin: is the combination appropriate and effective or inappropriate and too dangerous? Ann Pharmacother 42:790–805PubMed

23.

Porter A, Konstantino Y, Iakobishvili Z, Shachar L, Battler A, Hasdai D (2006) Short-term triple therapy with aspirin, warfarin, and a thienopyridine among patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 68:56–61PubMed

24.

Rubboli A, Saia F, Sciahbasi A, Bacchi-Reggiani ML, Steffanon L, Briguori C, Calabro P, Palmieri C, Rizzi A, Imperadore F, Sangiorgi GM, Valgimigli M, Carosio G, Steffenino G, Galvani M, Di Pasquale G, La Vecchia L, Maggioni AP, Bolognese L (2014) Outcome of patients on oral anticoagulation undergoing coronary artery stenting: data from discharge to 12 months in the Warfarin and coronary stenting (WAR-STENT) Registry. J Invasive Cardiol 26:563–569PubMed

25.

Nikolsky E, Mehran R, Dangas GD, Yu J, Parise H, Xu K, Pocock SJ, Stone GW (2012) Outcomes of patients treated with triple antithrombotic therapy after primary percutaneous coronary intervention for ST-elevation myocardial infarction (from the Harmonizing outcomes with revascularization and stents in acute myocardial infarction [HORIZONS-AMI] trial). Am J Cardiol 109:831–838PubMed

26.

Lamberts M, Gislason GH, Olesen JB, Kristensen SL, Schjerning Olsen AM, Mikkelsen A, Christensen CB, Lip GY, Kober L, Torp-Pedersen C, Hansen ML (2013) Oral anticoagulation and antiplatelets in atrial fibrillation patients after myocardial infarction and coronary intervention. J Am Coll Cardiol 62:981–989PubMed

27.

Nelson JA, Vavalle JP, May CH, Zhang A, Newby LK, Shaw LK, Al-Khatib SM, Alexander JH, Granger CB, Lopes RD (2014) Warfarin use and long-term outcomes in patients with acute myocardial infarction and atrial fibrillation. J Thromb Thrombolysis 37:331–337PubMed

28.

Lopes RD, Elliott LE, White HD, Hochman JS, Van de Werf F, Ardissino D, Nielsen TT, Weaver WD, Widimsky P, Armstrong PW, Granger CB (2009) Antithrombotic therapy and outcomes of patients with atrial fibrillation following primary percutaneous coronary intervention: results from the APEX-AMI trial. Eur Heart J 30:2019–2028PubMedPubMedCentral

29.

Ozturk M, Ipekci A, Kiyak SK, Akdeniz YS, Aydin Y, Ikizceli I, Sogut O (2019) Bleeding complications in warfarin-treated patients admitted to the emergency department. J Clin Med Res 11:106–113PubMedPubMedCentral

30.

Lindh JD, Holm L, Dahl ML, Alfredsson L, Rane A (2008) Incidence and predictors of severe bleeding during warfarin treatment. J Thromb Thrombolysis 25:151–159PubMed

31.

Kawai H, Watanabe E, Yamamoto M, Harigaya H, Sano K, Takatsu H, Muramatsu T, Naruse H, Sobue Y, Motoyama S, Sarai M, Takahashi H, Arakawa T, Kan S, Sugiura A, Murohara T, Ozaki Y (2015) Major bleeding complications related to combined antithrombotic therapy in atrial fibrillation patients 12 months after coronary artery stenting. J Cardiol 65:197–202PubMed

32.

Bogacki P, Kablak-Ziembicka A, Bryniarski K, Wrotniak L, Ostrowska-Kaim E, Zmudka K, Przewlocki T (2016) Triple anticoagulation therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention—real life assessment. Postepy Kardiol Interwencyjnej 12:303–313PubMedPubMedCentral

33.

Kang DO, Yu CW, Kim HD, Cho JY, Joo HJ, Choi RK, Park JS, Lee HJ, Kim JS, Park JH, Hong SJ, Lim DS (2015) Triple antithrombotic therapy versus dual antiplatelet therapy in patients with atrial fibrillation undergoing drug-eluting stent implantation. Coron Artery Dis 26:372–380PubMed

34.

Stenestrand U, Lindback J, Wallentin L (2005) Anticoagulation therapy in atrial fibrillation in combination with acute myocardial infarction influences long-term outcome: a prospective cohort study from the Register of information and knowledge about Swedish heart intensive care admissions (RIKS-HIA). Circulation 112:3225–3231PubMed

35.

Gwyn JCV, Thomas MR, Kirchhof P (2017) Triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a viewpoint. Eur Heart J Cardiovasc Pharmacother 3:157–162PubMed

36.

Lopes RD, Pieper KS, Horton JR, Al-Khatib SM, Newby LK, Mehta RH, Van de Werf F, Armstrong PW, Mahaffey KW, Harrington RA, Ohman EM, White HD, Wallentin L, Granger CB (2008) Short- and long-term outcomes following atrial fibrillation in patients with acute coronary syndromes with or without ST-segment elevation. Heart 94:867–873PubMed

37.

Dries DL, Rosenberg YD, Waclawiw MA, Domanski MJ (1997) Ejection fraction and risk of thromboembolic events in patients with systolic dysfunction and sinus rhythm: evidence for gender differences in the studies of left ventricular dysfunction trials. J Am Coll Cardiol 29:1074–1080PubMed

38.

Freudenberger RS, Hellkamp AS, Halperin JL, Poole J, Anderson J, Johnson G, Mark DB, Lee KL, Bardy GH (2007) Risk of thromboembolism in heart failure: an analysis from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Circulation 115:2637–2641PubMed

39.

Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P (2012) 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 33:2719–2747PubMed

40.

Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimsky P (2017) 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 39(2):119–177

41.

Anand SS, Yusuf S (2003) Oral anticoagulants in patients with coronary artery disease. J Am Coll Cardiol 41:62s–69sPubMed

42.

Verheugt FW (2001) Warfarin for ischemic heart disease. Cardiol Rev 9:325–328PubMed

43.

Berger PB, Bhatt DL, Fuster V, Steg PG, Fox KA, Shao M, Brennan DM, Hacke W, Montalescot G, Steinhubl SR, Topol EJ (2010) Bleeding complications with dual antiplatelet therapy among patients with stable vascular disease or risk factors for vascular disease: results from the Clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance (CHARISMA) trial. Circulation 121:2575–2583PubMed

44.

Hilkens NA, Algra A, Kappelle LJ, Bath PM, Csiba L, Rothwell PM, Greving JP (2018) Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke. Neurology 90:e683–e689PubMedPubMedCentral

45.

Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann-Roth EM, Richardt G, Alt E, Schmitt C, Ulm K (1996) A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 334:1084–1089PubMed

46.

Alfredsson J, Roe MT (2015) Risks and benefits of triple oral anti-thrombotic therapies after acute coronary syndromes and percutaneous coronary intervention. Drug Saf 38:481–491PubMed

47.

Schwalm JD, Ahmad M, Salehian O, Eikelboom JW, Natarajan MK (2010) Warfarin after anterior myocardial infarction in current era of dual antiplatelet therapy: a randomized feasibility trial. J Thromb Thrombolysis 30:127–132PubMed

48.

Barbieri L, Verdoia M, Schaffer A, Suryapranata H, De Luca G (2016) Risk and benefits of triple therapy in patients undergoing coronary stent implantation requiring oral anticoagulation: a meta-analysis of 16 studies. Cardiovasc Drugs Ther 30:611–622PubMed

49.

Moser M, Olivier CB, Bode C (2014) Triple antithrombotic therapy in cardiac patients: more questions than answers. Eur Heart J 35:216–223PubMed

50.

Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, Adriaenssens T, Vrolix M, Heestermans AA, Vis MM, Tijsen JG, van 't Hof AW, ten Berg JM, (2013) Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 381:1107–1115PubMed

51.

Fiedler KA, Maeng M, Mehilli J, Schulz-Schupke S, Byrne RA, Sibbing D, Hoppmann P, Schneider S, Fusaro M, Ott I, Kristensen SD, Ibrahim T, Massberg S, Schunkert H, Laugwitz KL, Kastrati A, Sarafoff N (2015) Duration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent implantation: the ISAR-TRIPLE Trial. J Am Coll Cardiol 65:1619–1629PubMed

52.

Lopes RD, Rao M, Simon DN, Thomas L, Ansell J, Fonarow GC, Gersh BJ, Go AS, Hylek EM, Kowey P, Piccini JP, Singer DE, Chang P, Peterson ED, Mahaffey KW (2016) Triple vs dual antithrombotic therapy in patients with atrial fibrillation and coronary artery disease. Am J Med 129:592–599.e591PubMed

53.

Mennuni MG, Halperin JL, Bansilal S, Schoos MM, Theodoropoulos KN, Meelu OA, Sartori S, Giacoppo D, Bernelli C, Moreno PR, Krishnan P, Baber U, Lucarelli C, Dangas GD, Sharma SK, Kini AS, Tamburino C, Chieffo A, Colombo A, Presbitero P, Mehran R (2015) Balancing the risk of bleeding and stroke in patients with atrial fibrillation after percutaneous coronary intervention (from the AVIATOR Registry). Am J Cardiol 116:37–42PubMed

54.

Peterson BE, Bhatt DL (2018) Management of anticoagulation in patients with atrial fibrillation undergoing PCI: double or triple therapy? Curr Cardiol Rep 20:110PubMedPubMedCentral

55.

Wadell D, Jensen J, Englund E, Sjalander A (2018) Triple therapy after PCI—Warfarin treatment quality and bleeding risk. PLoS ONE 13:e0209187PubMedPubMedCentral

56.

Golwala HB, Cannon CP, Steg PG, Doros G, Qamar A, Ellis SG, Oldgren J, Ten Berg JM, Kimura T, Hohnloser SH, Lip GYH, Bhatt DL (1735a) Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials. Eur Heart J 39:1726–1735aPubMedPubMedCentral

57.

Syn NL, Wong AL, Lee SC, Teoh HL, Yip JWL, Seet RC, Yeo WT, Kristanto W, Bee PC, Poon LM, Marban P, Wu TS, Winther MD, Brunham LR, Soong R, Tai BC, Goh BC (2018) Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: a randomized controlled trial. BMC Med 16:104PubMedPubMedCentral

Title: Comparison of effects of triple antithrombotic therapy and dual antiplatelet therapy on long-term outcomes of acute myocardial infarction
Authors: Mei-Tzu Wang
Cheng Chung Hung
Kun-Chang Lin
Guang-Yuan Mar
Shu-Hung Kuo
Cheng-Hung Chiang
Chin-Chang Cheng
Feng-You Kuo
Hsing-Li Liang
Wei-Chun Huang
Publication date: 01-03-2021
Publisher: Springer Japan
Keywords: Gastrointestinal Bleeding
Clopidogrel
Myocardial Infarction
Atrial Fibrillation
Warfarin
Published in: Heart and Vessels / Issue 3/2021
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-020-01708-8

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

At a glance: The STEP trials

Springer Medicine

Comparison of effects of triple antithrombotic therapy and dual antiplatelet therapy on long-term outcomes of acute myocardial infarction

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2021

Impact of high-dose statin on cardiovascular outcomes in real-world patients with ST-elevation acute myocardial infarction

Efficacy of three-dimensional road mapping by fusion of computed tomography angiography and fluoroscopy in endovascular treatment of aorto-iliac chronic total occlusion

Implication of urine aquaporin-2 levels following cardiac surgery

Safety, effectiveness and mid-term follow-up in 136 consecutive patients with moderate to severely calcified lesions undergoing phoenix atherectomy

Trajectory of renal function change and kidney injury after percutaneous coronary intervention in patients with stable coronary artery disease

Fibroblast growth factor 23 (FGF23) level is associated with ultrafiltration rate in patients on hemodialysis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page