The main goal of this study was to identify patients with atrial fibrillation and indication for anticoagulation undergoing percutaneous coronary intervention (PCI) who might benefit from extended triple antithrombotic therapy (TAT). The authors proposed a novel clinical risk score to select patients at high thrombotic risk.
- A post hoc subanalysis of the RE-DUAL PCI trial.
- The composite ischaemic endpoint was defined as cardiovascular death, MI, ST (definite or probable according to Academic Research Consortium [BARC] criteria) or ischaemic stroke.
- The bleeding endpoint was defined as the first BARC 2, 3 or 5 bleeding within 365 days.
- The follow-up was truncated after the first event (either ischaemic or bleeding event) or after one year in the absence of adverse events.
- Groups were compared according to intention-to-treat protocol.
- The benefit evaluation of different therapy strategies (TAT vs. DAT) in patients at higher thrombotic risk was performed comparing observed risks within the different risk categories and risk scores of ischaemic events, bleeding, and mortality.
- Internal and external validation was performed.
- A total of 2,725 patients were included in the analysis.
- 5% of the cohort underwent PCI for the indication of ACS.
- The composite ischaemic endpoint occurred in 209 patients (7.7%).
- Patients with an ischaemic event during follow-up were more likely to have a medical history of MI, heart failure, diabetes, renal failure, multivessel coronary disease, peripheral artery disease or prior stroke and were more likely to have presented with ACS. They also had lower LVEF, lower haemoglobin levels, and higher white blood cell counts, platelet counts and creatinine clearance.
- BARC 2, 3 or 5 bleedings were documented in 520 patients (19.1%).
- The simplified risk score contained six clinical variables (LVEF, 3-vessel disease, MI as indicated for index PCI, history of PAD, platelet count ³ 400x109/L, eGFR ³ 90ml/min). A certain number of points is given for each variable (from +3 to -1).
- In patients with score <5 classified as low and intermediate risk the use of TAT was significantly associated with higher bleeding rates than DAT (25.6% vs. 15.1%, p<0.001) without benefits regarding ischaemic endpoints.
- In patients with high risk (score ≥5) the use of TAT was related with significantly less myocardial infarction and stent thrombosis (6.3% vs. 21.0%, p=0.041) without higher bleeding rates.
- Thrombotic risk in high-risk patients (score ≥5) was significantly higher as compared to the remainder of the cohort (16.3% vs 6.7%, p=0.001).
- The discriminatory capacity of the ischaemic model was fair (C-statistic 0.68, 95% CI: 0.64-0.72) with better accuracy for the composite ischaemic endpoints compared to CHA2DS2-VASc scoring in the REDUAL PCI cohort (C-statistic 0.58, 95% CI: 0.54-0.62). An external validation was similar to the internal results (C-statistic 0.63, 95% CI: 0.56-0.70).
Both the 2020 NSTE-ACS and the atrial fibrillation guidelines recommend shortening the triple antiplatelet therapy following PCI up to 7 days or until the patient’s discharge (whichever comes first). These recommendations were introduced in order to reduce bleeding complications in this group of patients (as demonstrated in the ENTRUST-AF PCI study) without increasing thrombotic events (as described in the WOEST study). The guidelines allow for the extension of TAT up to one month in patients at increased risk of ischaemic complications. Therefore, the ability to identify patients with high thrombotic risk is crucial. The definition of such patients is imprecise and is usually based on the assessment of clinical and technical components.
A post hoc subanalysis of the REDUAL PCI trial showed that in the great majority of patients, the strategy of early termination of TAT and continuation of DAT brings tangible benefits in terms of effective protection against ischaemic events combined with reduction of the bleeding risk. Nevertheless, in clinical practice, there is still a small group of patients who require prolongation of TAT.
In the mentioned study approximately 5% of patients were at high-risk of thrombotic events and may still benefit from the extension of TAT up to 1 month following PCI. Therefore, dedicated tool to identify patient at high thrombotic risk should facilitate their proper selection. A score proposed in the described study is based on easily accessible clinical data, which may facilitate its application daily practice. However, further research is required before its clinical implementation.
Despite the fact that this score was validated both internally and externally with a satisfactory effect, it is necessary to acknowledge its significant limitations caused by the population enrolled into the REDUAL PCI trial. One of the major limitations is that patients in TAT arm were treated with VKA, which is not currently standard therapy and could have potentially played role in the increased risk of bleeding complications. Therefore, It is necessary to evaluate the score's performance for other therapeutic regimens and further external validation in randomized controlled trials.