Author + information
- Intensive Cardiac Care Unit and Cardiology Department, Centre Hospitalier Regional Universitaire de Tours & Tours University, Loire Valley Cardiovascular Collaboration, Tours, France
- ↵∗Address for correspondence:
Dr. Denis Angoulvant, USCI Cardiologie, Hôpital Trousseau, CHRU de Tours, 37000 Tours, France.
Dual antiplatelet therapy (DAPT) that combines low-dose aspirin and a P2Y12 inhibitor aims at preventing stent thrombosis, myocardial infarction, and stroke. It is recommended after coronary stent implantation for both stable coronary artery disease and after acute coronary syndrome (ACS). Optimal DAPT duration after coronary stent implantation remains a daily challenge for physicians. The summary of evidence from randomized clinical trials suggests that DAPT duration after drug-eluting stent implantation correlates with a lower incidence of ischemic events at the expense of increased bleeding (1).
The need for an accurate tool to estimate individual bleeding risk among patients after coronary stent implantation arose from these observations and was reinforced by international guidelines recommendations. Retrospective analysis showed that many variables might help distinguish between patients likely to benefit from prolonged DAPT from those likely to experience bleeding complications. Older age, ACS at presentation, third-generation drug-eluting stents, complexity of coronary lesions, complexity of the percutaneous coronary intervention (PCI) procedure, stents lengths and diameters, left ventricular ejection fraction, active smoking, and comorbidities (e.g., diabetes mellitus and reduced glomerular filtration rate) were shown to influence the individual response of the patient to DAPT. Several scores were retrospectively derived from randomized clinical trials to estimate the individual benefit−risk balance of prolonged DAPT after coronary stent implantation. Among them, the DAPT score was the first to suggest that a benefit of prolonged DAPT might be anticipated in a subset of patients who did not experience major bleeding or ischemic events within the year following PCI (2). The major limitations of this score are the absence of a prospective validation and the delayed time of decision for optimal DAPT duration 1 year after stent implantation.
In 2017, Costa et al. (3) derived the PRECISE-DAPT (PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy) prediction algorithm for out-of-hospital bleeding in patients treated with DAPT. The score consists of 5 bedside variables (age, creatinine clearance, hemoglobin, white blood cell count, and previous spontaneous bleeding) that were shown to predict individual bleeding risk at the time of DAPT initiation, which helps physicians to better anticipate optimal DAPT duration after coronary stent implantation. The 2017 European Society of Cardiology guidelines on DAPT endorsed the use of the PRECISE-DAPT score to estimate bleeding risk, recommending a shorter treatment duration (3 to 6 months) than a 12-month treatment duration in patients deemed to be a high bleeding risk (PRECISE-DAPT ≥25) (4). The bleeding risk appeared predominant in the decision of DAPT duration, which left unanswered questions for patients at high ischemic risk, such as those with complex coronary lesions, complex PCI procedures, and/or ACS at presentation.
The new publication by Costa et al. (5) in this issue of the Journal brings new insights to the cardiovascular community. In this new analysis of the PRECISE-DAPT population, the investigators compared 4 subgroups by combining high (≥25) or non-high (<25) bleeding risk according to the PRECISE-DAPT score and high (≥1 criteria) or non-high (0 criterion) ischemic risk according to PCI complexity (criteria included PCI with ≥3 stents implanted, ≥3 lesions treated, 3 coronary vessels treated, bifurcation with 2 stents implanted, total stent length >60 mm, and treatment of a chronic total occlusion). The investigators found that, regardless of ischemic risk (PCI complexity), long-term DAPT was beneficial in patients with a non-high bleeding risk and not beneficial in patients with a high bleeding risk. As expected, an excess of bleeding was observed in high bleeding risk patients who received long-term DAPT. Interestingly, in the subgroup of patients with both high bleeding and high ischemic risks, no reduction of ischemic events was observed using prolonged DAPT. In this group, there was an unfavorable balance regarding the net clinical effect of DAPT, which considered myocardial infarction, definite stent thrombosis, stroke, target vessel revascularization, or Thrombolysis In Myocardial Infarction (TIMI) major and/or minor bleeding. The same observations were made after estimating high-risk patients based on ACS at presentation as an additional criterion. Although these data were retrospectively collected from a post hoc analysis, they suggested that even in high ischemic risk patients, bleeding risk remains the cornerstone of DAPT duration.
As discussed by the investigators, there is a question as to why prolonged DAPT did not reduce ischemic events in the high ischemic and high bleeding risks populations. They suggested that antiplatelet agents might not be the best drugs to prevent ischemic events in this population. The question of whether other antithrombotic agents might be more efficient to prevent ischemic events (e.g., ischemic stroke) arose. The high bleeding risk population described in the paper had significantly higher figures in all components of the CHA2DS2-VASc score (coronary artery disease, age 75 years or older, hypertension, diabetes mellitus, lower left ventricle ejection fraction, and previous stroke). This might be of importance because the CHA2DS2-VASc score, which was developed to estimate stroke risk in nonvalvular atrial fibrillation patients, was also shown to be a predictor of cerebrovascular events in coronary artery disease patients without atrial fibrillation (6). The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial suggested that among patients with atherosclerotic cardiovascular disease, the combination of low-dose aspirin with a low dose of the selective direct factor Xa inhibitor rivaroxaban significantly reduced ischemic stroke incidence compared with aspirin alone (7). Although the number of ischemic strokes was not reported in this new analysis of the PRECISE-DAPT study, it could be hypothesized that it might have significantly contributed to the increased incidence of the combined endpoint of myocardial infarction, definite stent thrombosis, and stroke that was not prevented in the high ischemic and high bleeding risks group.
The robustness of the PRECISE-DAPT risk score could be questioned because it was retrospectively derived and validated from previous studies. Abu-Assi et al. (8) retrospectively investigated both PRECISE-DAPT and PARIS (patterns of non-adherence to antiplatelet regimens in stented patients) risk scores for predicting 1-year out-of-hospital bleeding after PCI in a Spanish cohort of ACS patients. They concluded that both scores were fairly to moderately effective for the prediction of bleeding, with the PARIS risk score being more efficient than the PRECISE-DAPT for discriminating patients who experienced BARC (Bleeding Academic Research Consortium) severe bleeding. The discrepancy between studies might be related to differences in populations (ACS only in the Spanish cohort), drug regimen, stent generation, and bleeding events classification (TIMI vs. BARC). There is obviously a need for prospective evaluation of these scores in future clinical trials.
The study by Costa et al. (5) is nonetheless a major signal for interventional cardiologists willing to individualize post-PCI DAPT duration. At the time of patients’ discharge after coronary stent implantation, interventional cardiologists are encouraged to anticipate DAPT duration that may be subsequently followed up by other physicians. A discharge letter recommending the individual optimal DAPT duration based on the hemorrhagic risk evaluation may be beneficial to reduce both ischemic and bleeding risks. This, of course, is hypothetical; the strategy proposed by Costa et al. (5) in this issue of the Journal deserves to be tested in a prospective randomized trial. In future trials, investigators may want to investigate risk-based antithrombotic strategies as well as alternative strategies, such as DAPT versus low-dose aspirin, combined with a low-dose factor Xa inhibitor.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Angoulvant has been a consultant/speaker for AstraZeneca, Bayer, Amgen, Sanofi, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, Servier, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
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