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

Francesco Costa, David van Klaveren, Stefan James, Dik Heg, Lorenz Räber, Fausto Feres, Thomas Pilgrim, Myeong Ki Hong, Hyo Soo Kim, Antonio Colombo, Philippe Gabriel Steg, Thomas Zanchin, Tullio Palmerini, Lars Wallentin, Deepak L. Bhatt, Gregg W. Stone, Stephan Windecker, Ewout W. Steyerberg, Marco Valgimigli

Research output: Contribution to journalArticle

246 Citations (Scopus)

Abstract

Background Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk. Findings The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61–0·85) in the derivation cohort, and 0·70 (0·65–0·74) in the PLATO trial validation cohort and 0·66 (0·61–0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction=0·007), and exerted a significant ischaemic benefit only in this latter group. Interpretation The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. Funding None.

Original languageEnglish
Pages (from-to)1025-1034
Number of pages10
JournalThe Lancet
Volume389
Issue number10073
DOIs
Publication statusPublished - 2017 Mar 11

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Stents
Clinical Trials
Hemorrhage
Therapeutics
clopidogrel
Aspirin
Registries
Thrombosis
Myocardial Infarction
Datasets
Percutaneous Coronary Intervention
Leukocyte Count
Creatinine
Hemoglobins
Blood Platelets
Ischemia
Randomized Controlled Trials
Guidelines

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Costa, Francesco ; van Klaveren, David ; James, Stefan ; Heg, Dik ; Räber, Lorenz ; Feres, Fausto ; Pilgrim, Thomas ; Hong, Myeong Ki ; Kim, Hyo Soo ; Colombo, Antonio ; Steg, Philippe Gabriel ; Zanchin, Thomas ; Palmerini, Tullio ; Wallentin, Lars ; Bhatt, Deepak L. ; Stone, Gregg W. ; Windecker, Stephan ; Steyerberg, Ewout W. ; Valgimigli, Marco. / 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. In: The Lancet. 2017 ; Vol. 389, No. 10073. pp. 1025-1034.
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abstract = "Background Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk. Findings The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95{\%} CI 0·61–0·85) in the derivation cohort, and 0·70 (0·65–0·74) in the PLATO trial validation cohort and 0·66 (0·61–0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction=0·007), and exerted a significant ischaemic benefit only in this latter group. Interpretation The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. Funding None.",
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Costa, F, van Klaveren, D, James, S, Heg, D, Räber, L, Feres, F, Pilgrim, T, Hong, MK, Kim, HS, Colombo, A, Steg, PG, Zanchin, T, Palmerini, T, Wallentin, L, Bhatt, DL, Stone, GW, Windecker, S, Steyerberg, EW & Valgimigli, M 2017, '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', The Lancet, vol. 389, no. 10073, pp. 1025-1034. https://doi.org/10.1016/S0140-6736(17)30397-5

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. / Costa, Francesco; van Klaveren, David; James, Stefan; Heg, Dik; Räber, Lorenz; Feres, Fausto; Pilgrim, Thomas; Hong, Myeong Ki; Kim, Hyo Soo; Colombo, Antonio; Steg, Philippe Gabriel; Zanchin, Thomas; Palmerini, Tullio; Wallentin, Lars; Bhatt, Deepak L.; Stone, Gregg W.; Windecker, Stephan; Steyerberg, Ewout W.; Valgimigli, Marco.

In: The Lancet, Vol. 389, No. 10073, 11.03.2017, p. 1025-1034.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score

T2 - a pooled analysis of individual-patient datasets from clinical trials

AU - Costa, Francesco

AU - van Klaveren, David

AU - James, Stefan

AU - Heg, Dik

AU - Räber, Lorenz

AU - Feres, Fausto

AU - Pilgrim, Thomas

AU - Hong, Myeong Ki

AU - Kim, Hyo Soo

AU - Colombo, Antonio

AU - Steg, Philippe Gabriel

AU - Zanchin, Thomas

AU - Palmerini, Tullio

AU - Wallentin, Lars

AU - Bhatt, Deepak L.

AU - Stone, Gregg W.

AU - Windecker, Stephan

AU - Steyerberg, Ewout W.

AU - Valgimigli, Marco

PY - 2017/3/11

Y1 - 2017/3/11

N2 - Background Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk. Findings The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61–0·85) in the derivation cohort, and 0·70 (0·65–0·74) in the PLATO trial validation cohort and 0·66 (0·61–0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction=0·007), and exerted a significant ischaemic benefit only in this latter group. Interpretation The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. Funding None.

AB - Background Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk. Findings The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61–0·85) in the derivation cohort, and 0·70 (0·65–0·74) in the PLATO trial validation cohort and 0·66 (0·61–0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction=0·007), and exerted a significant ischaemic benefit only in this latter group. Interpretation The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. Funding None.

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