Triple Therapy Among Older Patients With AMI and AF
Triple Therapy Among Older Patients With AMI and AF
Background Antithrombotic therapy for acute myocardial infarction (MI) with atrial fibrillation (AF) among higher risk older patients treated with percutaneous coronary intervention (PCI) remains unclear.
Objectives This study sought to determine appropriate antithrombotic therapy for acute MI patients with AF treated with PCI.
Methods We examined 4,959 patients ≥65 years of age with acute MI and AF who underwent coronary stenting (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines). The primary effectiveness outcome was 2-year major adverse cardiac events (MACE) comprising death, readmission for MI, or stroke; the primary safety outcome was bleeding readmission. Outcomes with dual antiplatelet therapy (DAPT) or triple therapy (DAPT plus warfarin) were compared using Cox proportional hazard modeling with inverse probability-weighted propensity adjustment.
Results Among 4,959 patients, 27.6% (n = 1,370) were discharged on triple therapy. Relative to DAPT, patients on triple therapy had a similar risk of MACE (adjusted hazard ratio [HR]: 0.99 [95% confidence interval (CI): 0.86 to 1.16]) but significantly greater risk of bleeding requiring hospitalization (adjusted HR: 1.61 [95% CI: 1.31 to 1.97]) and greater risk of intracranial hemorrhage (adjusted HR: 2.04 [95% CI: 1.25 to 3.34]). Of 1,591 Medicare Part D patients, 90-day post-discharge warfarin persistence among patients discharged on warfarin was 93.2% (n = 412). Results of 90-day landmark analyses comparing triple therapy versus DAPT in patients persistently on warfarin versus those not discharged on warfarin who had not filled a warfarin prescription were similar to our primary findings.
Conclusions Approximately 1 in 4 older AF patients undergoing PCI for MI were discharged on triple therapy. Those receiving triple therapy versus DAPT had higher rates of major bleeding without a measurable difference in composite MI, death, or stroke.
Selection of the optimal antithrombotic regimen for patients with acute myocardial infarction (MI) who have concomitant atrial fibrillation (AF) and are treated with percutaneous coronary intervention (PCI) presents a therapeutic challenge. Current guidelines for the management of AF recommend anticoagulation for thromboembolic prophylaxis in AF patients who are at average or higher risk for stroke but not at prohibitive risk for bleeding. Guidelines for the management of acute MI and PCI patients recommend treatment with dual antiplatelet therapy (DAPT) to reduce the risks of major adverse cardiac events (MACE) and stent thrombosis; however, clinicians may be reluctant to treat AF patients with concurrent indications for DAPT by using the combination of warfarin, aspirin, and clopidogrel (triple therapy) due to the high bleeding risk associated with this regimen.
Although previous studies have found that bleeding risk is higher among patients receiving triple therapy, some data also suggest a lower risk of MACE among patients treated with triple therapy relative to DAPT. Given the paucity of randomized data, studies have shown variability in anticoagulant agent use according to the predicted risks of stroke and bleeding in this patient population. Therapeutic decisions for older patients with AF and coronary artery disease may be especially challenging. Older patients in particular are at greater risk for AF-related stroke and recurrent events after acute MI but also have a higher risk for bleeding events. Importantly, the older population has been excluded from or underrepresented in clinical trials and, therefore, remains understudied.
Abstract and Introduction
Abstract
Background Antithrombotic therapy for acute myocardial infarction (MI) with atrial fibrillation (AF) among higher risk older patients treated with percutaneous coronary intervention (PCI) remains unclear.
Objectives This study sought to determine appropriate antithrombotic therapy for acute MI patients with AF treated with PCI.
Methods We examined 4,959 patients ≥65 years of age with acute MI and AF who underwent coronary stenting (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines). The primary effectiveness outcome was 2-year major adverse cardiac events (MACE) comprising death, readmission for MI, or stroke; the primary safety outcome was bleeding readmission. Outcomes with dual antiplatelet therapy (DAPT) or triple therapy (DAPT plus warfarin) were compared using Cox proportional hazard modeling with inverse probability-weighted propensity adjustment.
Results Among 4,959 patients, 27.6% (n = 1,370) were discharged on triple therapy. Relative to DAPT, patients on triple therapy had a similar risk of MACE (adjusted hazard ratio [HR]: 0.99 [95% confidence interval (CI): 0.86 to 1.16]) but significantly greater risk of bleeding requiring hospitalization (adjusted HR: 1.61 [95% CI: 1.31 to 1.97]) and greater risk of intracranial hemorrhage (adjusted HR: 2.04 [95% CI: 1.25 to 3.34]). Of 1,591 Medicare Part D patients, 90-day post-discharge warfarin persistence among patients discharged on warfarin was 93.2% (n = 412). Results of 90-day landmark analyses comparing triple therapy versus DAPT in patients persistently on warfarin versus those not discharged on warfarin who had not filled a warfarin prescription were similar to our primary findings.
Conclusions Approximately 1 in 4 older AF patients undergoing PCI for MI were discharged on triple therapy. Those receiving triple therapy versus DAPT had higher rates of major bleeding without a measurable difference in composite MI, death, or stroke.
Introduction
Selection of the optimal antithrombotic regimen for patients with acute myocardial infarction (MI) who have concomitant atrial fibrillation (AF) and are treated with percutaneous coronary intervention (PCI) presents a therapeutic challenge. Current guidelines for the management of AF recommend anticoagulation for thromboembolic prophylaxis in AF patients who are at average or higher risk for stroke but not at prohibitive risk for bleeding. Guidelines for the management of acute MI and PCI patients recommend treatment with dual antiplatelet therapy (DAPT) to reduce the risks of major adverse cardiac events (MACE) and stent thrombosis; however, clinicians may be reluctant to treat AF patients with concurrent indications for DAPT by using the combination of warfarin, aspirin, and clopidogrel (triple therapy) due to the high bleeding risk associated with this regimen.
Although previous studies have found that bleeding risk is higher among patients receiving triple therapy, some data also suggest a lower risk of MACE among patients treated with triple therapy relative to DAPT. Given the paucity of randomized data, studies have shown variability in anticoagulant agent use according to the predicted risks of stroke and bleeding in this patient population. Therapeutic decisions for older patients with AF and coronary artery disease may be especially challenging. Older patients in particular are at greater risk for AF-related stroke and recurrent events after acute MI but also have a higher risk for bleeding events. Importantly, the older population has been excluded from or underrepresented in clinical trials and, therefore, remains understudied.
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