Net clinical benefit of different strategies of dual antiplatelet therapy in elderly patients: Data from the praise registry

Highlights

• Use of potent P2Y12 inhibitors after Acute Coronary Syndrome (ACS) are the standard of care.

• Safety and efficacy of potent P2Y12 inhibitors in elderly patient still is unclear.

• ≥75 year old patient treated with potent P2Y12 inhibitors have reduced risk of ischemic events such as recurrence of myocardial infarction comparing to Clopidogrel.

• The net effect of potent P2Y12 inhibitors on elderly patient after ACS is neutral due to increased risk of major bleeding comparing to Clopidogrel.

Abstract

Background

The safety and efficacy of potent P2Y12 inhibitors (Ticagrelor and Prasugrel) in dual antiplatelet therapy (DAPT) with aspirin in elderly acute coronary syndrome (ACS) patients remains unclear.

Methods

All ACS patients aged 75 years and older treated with Percutaneous Coronary Intervention (PCI) from PRAISE dataset were included. The safety and efficacy of Ticagrelor vs Clopidogrel was evaluated with inverse probability of treatment weighting (IPTW). Sensitivity analysis was performed for patients older or equal than 85 years old. All-cause mortality was the primary endpoint, while myocardial infarction (MI), Bleeding Academic Research Consortium (BARC) 3–5 bleedings and Major and Net Adverse Clinical and Cardiac Events (MACE and NACE) were the secondary ones.

Results

4287 patients were included, 3197 treated with Clopidogrel and 1090 with Ticagrelor. After 16 ± 3 months, Ticagrelor showed neutral effect on NACE and mortality (HR 0.98; 0.63–1.52, p = 0.94 and HR 0.38; 0.14–1.04, p = 0,06), reduced risk of MACE and MI (HR 0.82; 0.23–0.91, p = 0.03 and HR 0.43; 0.14–0.89, p = 0.04) and increased risk of BARC 3–5 bleeding (HR 2.14; 1.19–3.85, p = 0.001). In very elderly patients (≥85 years) Ticagrelor decreased risk of MI and increased risk of bleeding (HR 0.69; 0.22–0.95, p = 0.04 and HR 2.36; 1.02–5.52, p = 0.04, all 95%CI) with neutral effect on NACE and MACE.

Conclusions

In elderly ACS patients treated with PCI, Ticagrelor was associated with neutral effect on all-cause mortality, lower risk MACE and MI compared with Clopidogrel. Such benefit was counterbalanced by increased risk of major bleedings. These results were consistent among patients aged 85 years and older.

Introduction

Current guidelines recommend potent platelet inhibition by Prasugrel or Ticagrelor in patients with Acute Coronary Syndrome (ACS) regardless of patients' age [1], [2]. Sub-analysis from PLATO and from TRITON-TIMI trial showed that the safety and the clinical benefit of Prasugrel or Ticagrelor were consistent across different ages [3], [4]. However, the patients' mean age in these cohorts was 62 and 61 years, respectively, with only 15% of the included patients older than 75 years [5], [6].

Therefore, evidence about the safety and the efficacy of potent P2Y12 inhibitors compared with Clopidogrel in older patients are scant, especially regarding the known association between older age and bleeding events [7], [8]. Several observational cohort studies cast some doubts about the net clinical benefit of potent P2Y12 inhibitors in older patients. In the randomized Popular Age trial, Clopidogrel emerged as a favorable alternative to Ticagrelor in patients aged 70 years or older presenting with NSTE-ACS, leading to fewer bleeding events without an increase in a combined ischemic endpoint [9]. Similarly, results from a Swedish observational registry including patients older than 80 years demonstrated an increased incidence of bleedings and mortality in patients treated with Ticagrelor compared with Clopidogrel [10].

A matter of specific concern in this context is the increased risk of bleeding in older ACS patients, since it has been demonstrated that in a contemporary cohort of ACS patients bleeding was associated with a significantly increased risk of subsequent ischemic events and mortality regardless of antithrombotic strategy [11].

The aim of this study was to evaluate the efficacy and safety of potent P2Y12 inhibitors compared with Clopidogrel in patients aged 75 years and older in the PRAISE dataset, a large, international, multicenter registry.