Long-Term Use of Antiplatelet Therapy in Real-World Patients with Acute Myocardial Infarction: Insights from the PIPER Study

Abstract

The aim of this study was to assess long-term drug adherence and prognosis in real-world patients discharged on dual-antiplatelet therapy (DAPT) after acute myocardial infarction (AMI). A retrospective cohort analysis using administrative databases kept by eight local health units was performed. DAPT exposure (defined as ≥ 2 prescriptions), adherence, and the occurrence of major adverse events (MACE) were analyzed during a 36-month follow-up. The analysis included 11,101 patients who were discharged alive with a primary diagnosis of AMI. Of these, 5,919 patients (53.31%) were discharged on DAPT without a diagnosis of cancer or anemia, without transient DAPT discontinuation, and represented the study population. DAPT discontinuation occurred in 2,200 patients (37.2%) and in 1,995 (33.7%) after the first 6 and 12 months, respectively, whereas 423 patients (7.1%) were still on DAPT after 36 months. Patients who maintained DAPT up to 12 months had a significantly lower overall mortality, compared with patients who discontinued DAPT after 6 months. Exposure to DAPT at 3 years was associated with reduced all-cause mortality (hazard ratio [HR]: 0.067, 95% confidence interval [CI]: 0.027–0.162, p < 0.001) and reduced recurrent AMI (HR: 0.02, 95% CI: 0.003–0.173, p < 0.001). In conclusion, this study shows that prolonged DAPT over 12 months is maintained in a relevant number of patients after AMI. However, adherence to antiplatelet therapy in first 12 months after AMI is still unsatisfactory and efforts to enhance patients' compliance are warranted. Exposure to prolonged DAPT at 3 years seems to be associated with a significant reduction in all-cause mortality and AMI.

Keywords

acute myocardial infarction - antiplatelet therapy - adherence to treatment

Authors' Contributions

All authors contributed toward data analysis, drafting, and revising the manuscript and agree to be accountable for all aspects of the work.

Ethical Approval

This article does not contain any studies with animals performed by any of the authors.

Informed Consent

Informed consent is not required by the Local Health Unit (LHU) ethics committees for using encrypted retrospective information. No identifiers related to patients were provided to the researchers. This study was notified to the local ethics committee in each participating LHU according to the Italian law regarding the conduct of observational analysis, and the LHU Ethics Committees approved the study.

^* LHU group: Samanta Sonzogni, Rossana Piccinelli e Marco Gambera (LHU Bergamo); Isabella Ruggeri (LHU Milano 2); Giovanna Riccioni (LHU Roma 1); Fabrizio Quarta (LHU Lecce).

• References

• 1 Valgimigli M, Bueno H, Byrne RA. , et al; ESC Scientific Document Group; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 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). Eur Heart J 2018; 39 (03) 213-260
• 2 Ibanez B, James S, Agewall S. , et al; ESC Scientific Document Group. 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 2018; 39 (02) 119-177
• 3 Hamm CW, Bassand J-P, Agewall S. , et al; ESC Committee for Practice Guidelines. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32 (23) 2999-3054
• 4 Kereiakes DJ, Yeh RW, Massaro JM. , et al; Dual Antiplatelet Therapy (DAPT) Study Investigators. Antiplatelet therapy duration following bare metal or drug-eluting coronary stents: the dual antiplatelet therapy randomized clinical trial. JAMA 2015; 313 (11) 1113-1121
• 5 Bonaca MP, Bhatt DL, Cohen M. , et al; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372 (19) 1791-1800
• 6 Mathews R, Peterson ED, Honeycutt E. , et al. Early medication nonadherence after acute myocardial infarction: insights into actionable opportunities from the TReatment with ADP receptor iNhibitorS: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study. Circ Cardiovasc Qual Outcomes 2015; 8 (04) 347-356
• 7 Bonaca MP, Bhatt DL, Oude Ophuis T. , et al. Long-term tolerability of ticagrelor for the secondary prevention of major adverse cardiovascular events: a secondary analysis of the PEGASUS-TIMI 54 trial. JAMA Cardiol 2016; 1 (04) 425-432
• 8 Rossini R, Capodanno D, Lettieri C. , et al. Prevalence, predictors, and long-term prognosis of premature discontinuation of oral antiplatelet therapy after drug eluting stent implantation. Am J Cardiol 2011; 107 (02) 186-194
• 9 Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 2007; 297 (02) 177-186
• 10 Wilson SJ, Newby DE, Dawson D, Irving J, Berry C. Duration of dual antiplatelet therapy in acute coronary syndrome. Heart 2017; 103 (08) 573-580
• 11 Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. ; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345 (07) 494-502
• 12 Chen ZM, Jiang LX, Chen YP. , et al; COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005; 366 (9497): 1607-1621
• 13 Sabatine MS, Cannon CP, Gibson CM. , et al; CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005; 352 (12) 1179-1189
• 14 Wiviott SD, Braunwald E, McCabe CH. , et al; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357 (20) 2001-2015
• 15 Wallentin L, Becker RC, Budaj A. , et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361 (11) 1045-1057
• 16 Pfisterer M, Brunner-La Rocca HP, Buser PT. , et al; BASKET-LATE Investigators. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol 2006; 48 (12) 2584-2591
• 17 Eisenstein EL, Anstrom KJ, Kong DF. , et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA 2007; 297 (02) 159-168
• 18 Palmerini T, Biondi-Zoccai G, Della Riva D. , et al. Clinical outcomes with drug-eluting and bare-metal stents in patients with ST-segment elevation myocardial infarction: evidence from a comprehensive network meta-analysis. J Am Coll Cardiol 2013; 62 (06) 496-504
• 19 Stafford RS, Radley DC. The underutilization of cardiac medications of proven benefit, 1990 to 2002. J Am Coll Cardiol 2003; 41 (01) 56-61
• 20 Marcum ZA, Sevick MA, Handler SM. Medication nonadherence: a diagnosable and treatable medical condition. JAMA 2013; 309 (20) 2105-2106
• 21 Faxon D, Brown M. Antiplatelet therapy for postdischarge medical management of acute coronary syndrome. Am J Med 2008; 121 (03) 171-178
• 22 Lenzi J, Rucci P, Castaldini I. , et al. Does age modify the relationship between adherence to secondary prevention medications and mortality after acute myocardial infarction? A nested case-control study. Eur J Clin Pharmacol 2015; 71 (02) 243-250
• 23 Brar SS, Kim J, Brar SK. , et al. Long-term outcomes by clopidogrel duration and stent type in a diabetic population with de novo coronary artery lesions. J Am Coll Cardiol 2008; 51 (23) 2220-2227
• 24 Daemen J, Wenaweser P, Tsuchida K. , et al. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet 2007; 369 (9562): 667-678
• 25 Brown MT, Bussell JK. Medication adherence: WHO cares?. Mayo Clin Proc 2011; 86 (04) 304-314
• 26 Montalescot G, Sechtem U, Achenbach S. , et al; Task Force Members; ESC Committee for Practice Guidelines; Document Reviewers. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34 (38) 2949-3003
• 27 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 2016; 134 (10) e123-e155