Net clinical benefit of different strategies of dual antiplatelet therapy in elderly patients: Data from the praise registry
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.
Section snippets
Methods
The PRAISE dataset has been previously described [12]. Briefly, it consisted of patients admitted with ACS treated with Percutaneous Coronary Intervention (PCI) enrolled in the following registries/studies:
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BLEEMACS registry (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome, NCT02466854) including 15,401 consecutive ACS patients admitted between 2003 and 2014 at 15 tertiary hospitals in North and South America, Europe and Asia and treated
Results
Baseline characteristics of overall sample are described in Table 1. Out of 23,270 patients included in the PRAISE dataset, 4495 were aged 75 years and older. Of these, 3197 were treated with Clopidogrel, 1017 (78%) with Ticagrelor and 281 (22%) with prasugrel.
Discussion
The main findings of this large multicenter retrospective study comparing the efficacy and safety of DAPT therapy with Aspirin plus Ticagrelor versus Aspirin plus Clopidogrel in older ACS patients are the following:
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In patients aged ≥75 years Ticagrelor is associated with reduced incidence of recurrent MI, counterbalanced by an increased incidence of BARC 3–5 bleedings. Ticagrelor reduced risk of MACE, with a neutral effect on NACE.
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These results were consistent in the oldest patients (≥85 years
Funding
Nothing to declare.
Declaration of Competing Interest
Nothing to declare.
All the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their interpretation.
Acknowledgement
Nothing to declare.
References (27)
- et al.
Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial
Lancet
(2020) - et al.
Apixaban for prevention of acute ischemic safety events APPRAISE-2 steering committee and investigators. Clinical consequences of bleeding among individuals with a recent acute coronary syndrome: insights from the APPRAISE-2 trial
Am. Heart J.
(2019 Sep) - et al.
Machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE): a modelling study of pooled datasets
Lancet
(2021) - et al.
Are propensity scores really superior to standard multivariable analysis?
Contemp. Clin. Trials
(2011) - et al.
Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: insights from the BleeMACS and RENAMI registries
Am. Heart J.
(2020 Feb) - et al.
Efficacy and safety of potent platelet P2Y12 receptor inhibitors in elderly versus nonelderly patients with acute coronary syndrome: a systematic review and meta-analysis
Am. Heart J.
(2018 Jan) - et al.
Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study
Lancet Lond. Engl.
(2017) - et al.
PRECISE-DAPT Study Investigators.Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials
Lancet
(2017) - et al.
Coronary thrombosis and major bleeding after PCI with drug-eluting stents: risk scores from PARIS
J. Am. Coll. Cardiol.
(2016) - et al.
Optimised care of elderly patients with acute coronary syndrome
Eur. Heart J. Acute Cardiovasc. Care
(2018)
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 in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC)
Eur. Heart J.
Predictors of bleeding and time dependence of association of bleeding with mortality
Circulation
Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes
Circ. Cardiovasc. Qual. Outcomes
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