Triple Therapy Among Older Patients With AMI and AF
Triple Therapy Among Older Patients With AMI and AF
Among 4,959 MI patients presenting with a history of AF who were treated with PCI, 27.6% (n = 1,370) were discharged on triple therapy, and 72.4% (n = 3,589) were discharged on DAPT (Table 1). Compared with patients prescribed DAPT at discharge, those receiving triple therapy were more often male and more frequently had a history of PCI or CABG, prior stroke, and recent AF or atrial flutter. Patients discharged on triple therapy were frequently already on warfarin before admission, whereas those discharged on DAPT were more likely to have had an in-hospital major bleeding event. Use of triple therapy increased with higher predicted stroke risk (p for trend < 0.0001) but was not associated with predicted bleeding risk (p for trend = 0.18) (Figure 2). Patients in the triple therapy group also more often presented with NSTEMI than STEMI and more often had a left ventricular ejection fraction ≤40%. There was greater use of glycoprotein IIb/IIIa inhibitors among patients discharged on DAPT, whereas patients in the triple therapy group more often received bivalirudin during their PCI. Patients prescribed triple therapy who underwent PCI for NSTEMI were less likely to undergo DES implantation, whereas DES use for primary PCI among STEMI patients was similar between the DAPT and triple therapy groups.
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Figure 2.
Warfarin Use According to Risk of Stroke and Bleeding
Use of triple therapy according to: (A) stroke risk assessed by using the CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes, prior stroke or transient ischemic attack) score; and (B) bleeding risk assessed by using the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) score.
Clinical outcomes were examined according to discharge prescription of triple therapy versus DAPT (Figure 3). Unadjusted cumulative incidence rates of 2-year post-discharge MACE between triple therapy and DAPT groups were similar (32.6% vs. 32.7%; p = 0.99). Unadjusted cumulative incidence rates of the individual MACE component endpoints were also similar between patients discharged on triple therapy versus DAPT: all-cause mortality (23.8% vs. 24.8%; p = 0.70), MI readmission (8.5% vs. 8.1%; p = 0.54), and stroke readmission (4.7% vs. 5.3%; p = 0.23). The unadjusted cumulative incidence of ischemic stroke was lower for patients discharged on triple therapy versus DAPT (3.2% vs. 4.7%; p = 0.02). After adjustment for patient, treatment, and hospital characteristics, there was no association of triple therapy with 2-year MACE (adjusted HR: 0.99 [95% CI: 0.86 to 1.16]; p = 0.94), all-cause mortality (adjusted HR: 0.98 [95% CI: 0.83 to 1.16]; p = 0.82), MI readmission (adjusted HR: 1.03 [95% CI: 0.79 to 1.33]; p = 0.83), or stroke readmission (adjusted HR: 0.85 [95% CI: 0.58 to 1.23]; p = 0.38). The adjusted HR for ischemic stroke was lower at 0.66 with triple therapy compared with DAPT; however, this comparison remained nonstatistically significant (95% CI: 0.41 to 1.06; p = 0.09).
(Enlarge Image)
Figure 3.
MACE Outcomes According to Use of Triple Therapy Versus DAPT
Cumulative incidence curves for triple therapy versus DAPT for: (A) major adverse cardiac events (MACE); (B) all-cause mortality; (C) myocardial infarction (MI); (D) stroke (ischemic and hemorrhagic); and (E) ischemic stroke. Abbreviations as in Figure 1.
The cumulative incidence of bleeding requiring hospitalization within 2 years post-discharge was significantly higher for patients discharged on triple therapy compared with DAPT (17.6% vs. 11.0%; p < 0.0001), with curves diverging early after discharge (Figure 4A). This association persisted after adjustment for case-mix, treatment, and hospital features (adjusted HR: 1.61 [95% CI: 1.31 to 1.97]; p < 0.0001). Unadjusted cumulative incidence of intracranial hemorrhage was higher for patients treated with triple therapy versus DAPT (3.4% vs. 1.5%; p < 0.001) (Figure 4B). After adjustment, triple therapy remained significantly associated with intracranial hemorrhage (adjusted HR: 2.04 [95% CI: 1.25 to 3.34]; p < 0.01).
(Enlarge Image)
Figure 4.
Bleeding Outcomes According to Triple Therapy Versus DAPT
Cumulative incidence curves for triple therapy versus DAPT for: (A) bleeding readmission and (B) intracranial hemorrhage. Abbreviation as in Figure 1.
Several subgroup analyses were performed. After adjustment, the association of triple therapy with risk of 2-year MACE was similar between older (≥75 years) versus younger patients, men versus women, patients with high (CHADS2 score cutoffs of >2 and ≥4) versus low predicted stroke risk, patients with shorter versus longer duration of AF, patients treated with DES versus bare-metal stent, and patients presenting with NSTEMI versus STEMI (p for interaction >0.05 for all) (Figure 5A). Among these same subgroups, results were also consistent when examining triple therapy and risk of 2-year bleeding readmissions (adjusted p for interaction >0.05) (Figure 5B).
(Enlarge Image)
Figure 5.
MACE and Bleeding Outcomes Among Selected Subgroups
Shown in the forest plot are outcomes for: (A) MACE; and (B) bleeding readmission comparing triple therapy versus DAPT among patients according to age, sex, CHADS2 score, ATRIA score, atrial fibrillation/flutter duration, stent type, and MI type. BMS = bare-metal stent(s); CI = confidence interval; DES = drug-eluting stent(s); HR = hazard ratio; NSTEMI = non–ST-segment elevation myocardial infarction; STEMI = ST-segment elevation myocardial infarction; other abbreviations as in Figures 1 to 4.
A total of 1,591 patients in our study had Medicare Part D prescription coverage before discharge. Among this cohort, 27.8% (n = 442) were discharged on warfarin, and 72.2% (n = 1,149) were discharged on DAPT only. Post-discharge antithrombotic therapy use was examined (Table 2). Within 90 days post-discharge, the rates of warfarin persistence among patients discharged on warfarin was 93.2% (n = 412), and P2Y12 inhibitor persistence among patients discharged on DAPT was 94.7% (n = 1,088). Among patients not discharged on warfarin, 11.4% (n = 232) had filled a warfarin prescription within 90 days of discharge. Of the 425 patients with a CHADS2 score >2 who were not discharged on warfarin, 12.7% had filled a warfarin prescription within 90 days of discharge. In a landmark analysis starting 90 days post-discharge, we found that patients discharged on warfarin who were persistently taking warfarin at that time had a similar 2-year risk of MACE (adjusted HR: 0.96 [95% CI: 0.67 to 1.36]; p = 0.81) and a trend for higher risk of bleeding (adjusted HR: 1.50 [95% CI: 0.92 to 2.46]; p = 0.10) compared with patients not discharged on warfarin who had not filled a warfarin prescription during that time.
Results
Patient and In-hospital Characteristics Among DAPT Versus Triple Therapy Groups
Among 4,959 MI patients presenting with a history of AF who were treated with PCI, 27.6% (n = 1,370) were discharged on triple therapy, and 72.4% (n = 3,589) were discharged on DAPT (Table 1). Compared with patients prescribed DAPT at discharge, those receiving triple therapy were more often male and more frequently had a history of PCI or CABG, prior stroke, and recent AF or atrial flutter. Patients discharged on triple therapy were frequently already on warfarin before admission, whereas those discharged on DAPT were more likely to have had an in-hospital major bleeding event. Use of triple therapy increased with higher predicted stroke risk (p for trend < 0.0001) but was not associated with predicted bleeding risk (p for trend = 0.18) (Figure 2). Patients in the triple therapy group also more often presented with NSTEMI than STEMI and more often had a left ventricular ejection fraction ≤40%. There was greater use of glycoprotein IIb/IIIa inhibitors among patients discharged on DAPT, whereas patients in the triple therapy group more often received bivalirudin during their PCI. Patients prescribed triple therapy who underwent PCI for NSTEMI were less likely to undergo DES implantation, whereas DES use for primary PCI among STEMI patients was similar between the DAPT and triple therapy groups.
(Enlarge Image)
Figure 2.
Warfarin Use According to Risk of Stroke and Bleeding
Use of triple therapy according to: (A) stroke risk assessed by using the CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes, prior stroke or transient ischemic attack) score; and (B) bleeding risk assessed by using the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) score.
Clinical Outcomes According to Discharge Antithrombotic Regimen
Clinical outcomes were examined according to discharge prescription of triple therapy versus DAPT (Figure 3). Unadjusted cumulative incidence rates of 2-year post-discharge MACE between triple therapy and DAPT groups were similar (32.6% vs. 32.7%; p = 0.99). Unadjusted cumulative incidence rates of the individual MACE component endpoints were also similar between patients discharged on triple therapy versus DAPT: all-cause mortality (23.8% vs. 24.8%; p = 0.70), MI readmission (8.5% vs. 8.1%; p = 0.54), and stroke readmission (4.7% vs. 5.3%; p = 0.23). The unadjusted cumulative incidence of ischemic stroke was lower for patients discharged on triple therapy versus DAPT (3.2% vs. 4.7%; p = 0.02). After adjustment for patient, treatment, and hospital characteristics, there was no association of triple therapy with 2-year MACE (adjusted HR: 0.99 [95% CI: 0.86 to 1.16]; p = 0.94), all-cause mortality (adjusted HR: 0.98 [95% CI: 0.83 to 1.16]; p = 0.82), MI readmission (adjusted HR: 1.03 [95% CI: 0.79 to 1.33]; p = 0.83), or stroke readmission (adjusted HR: 0.85 [95% CI: 0.58 to 1.23]; p = 0.38). The adjusted HR for ischemic stroke was lower at 0.66 with triple therapy compared with DAPT; however, this comparison remained nonstatistically significant (95% CI: 0.41 to 1.06; p = 0.09).
(Enlarge Image)
Figure 3.
MACE Outcomes According to Use of Triple Therapy Versus DAPT
Cumulative incidence curves for triple therapy versus DAPT for: (A) major adverse cardiac events (MACE); (B) all-cause mortality; (C) myocardial infarction (MI); (D) stroke (ischemic and hemorrhagic); and (E) ischemic stroke. Abbreviations as in Figure 1.
The cumulative incidence of bleeding requiring hospitalization within 2 years post-discharge was significantly higher for patients discharged on triple therapy compared with DAPT (17.6% vs. 11.0%; p < 0.0001), with curves diverging early after discharge (Figure 4A). This association persisted after adjustment for case-mix, treatment, and hospital features (adjusted HR: 1.61 [95% CI: 1.31 to 1.97]; p < 0.0001). Unadjusted cumulative incidence of intracranial hemorrhage was higher for patients treated with triple therapy versus DAPT (3.4% vs. 1.5%; p < 0.001) (Figure 4B). After adjustment, triple therapy remained significantly associated with intracranial hemorrhage (adjusted HR: 2.04 [95% CI: 1.25 to 3.34]; p < 0.01).
(Enlarge Image)
Figure 4.
Bleeding Outcomes According to Triple Therapy Versus DAPT
Cumulative incidence curves for triple therapy versus DAPT for: (A) bleeding readmission and (B) intracranial hemorrhage. Abbreviation as in Figure 1.
Secondary Analyses
Several subgroup analyses were performed. After adjustment, the association of triple therapy with risk of 2-year MACE was similar between older (≥75 years) versus younger patients, men versus women, patients with high (CHADS2 score cutoffs of >2 and ≥4) versus low predicted stroke risk, patients with shorter versus longer duration of AF, patients treated with DES versus bare-metal stent, and patients presenting with NSTEMI versus STEMI (p for interaction >0.05 for all) (Figure 5A). Among these same subgroups, results were also consistent when examining triple therapy and risk of 2-year bleeding readmissions (adjusted p for interaction >0.05) (Figure 5B).
(Enlarge Image)
Figure 5.
MACE and Bleeding Outcomes Among Selected Subgroups
Shown in the forest plot are outcomes for: (A) MACE; and (B) bleeding readmission comparing triple therapy versus DAPT among patients according to age, sex, CHADS2 score, ATRIA score, atrial fibrillation/flutter duration, stent type, and MI type. BMS = bare-metal stent(s); CI = confidence interval; DES = drug-eluting stent(s); HR = hazard ratio; NSTEMI = non–ST-segment elevation myocardial infarction; STEMI = ST-segment elevation myocardial infarction; other abbreviations as in Figures 1 to 4.
A total of 1,591 patients in our study had Medicare Part D prescription coverage before discharge. Among this cohort, 27.8% (n = 442) were discharged on warfarin, and 72.2% (n = 1,149) were discharged on DAPT only. Post-discharge antithrombotic therapy use was examined (Table 2). Within 90 days post-discharge, the rates of warfarin persistence among patients discharged on warfarin was 93.2% (n = 412), and P2Y12 inhibitor persistence among patients discharged on DAPT was 94.7% (n = 1,088). Among patients not discharged on warfarin, 11.4% (n = 232) had filled a warfarin prescription within 90 days of discharge. Of the 425 patients with a CHADS2 score >2 who were not discharged on warfarin, 12.7% had filled a warfarin prescription within 90 days of discharge. In a landmark analysis starting 90 days post-discharge, we found that patients discharged on warfarin who were persistently taking warfarin at that time had a similar 2-year risk of MACE (adjusted HR: 0.96 [95% CI: 0.67 to 1.36]; p = 0.81) and a trend for higher risk of bleeding (adjusted HR: 1.50 [95% CI: 0.92 to 2.46]; p = 0.10) compared with patients not discharged on warfarin who had not filled a warfarin prescription during that time.
