Optimal lenght of DAPT in different clinical scenarios After PCI with DES in the light of recent and ongoing studies Dr Grégoire Rangé / CH Chartres / France
DAPT duration depend on the evolution of risk s balance along time Bleeding Stent thrombosis D 0 D? D 365 = Switch DAPT to SAPT
Clinical and procedural factors associated with ischemic and bleeding risks (ACC 2016) Ischemic risk Advanced age ACS Prior MI Extensive CAD Diabetes CKD Risque TIS ACS Diabetes LVEF < 40 % 1 er génération DES ISR Bifurcation Stent undersized or deployed Small diameter or long Stent Hemorragic risk 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: Advanced age Female sex BMI <25 CKD Diabetes Oral anticoagulation Anémia History of prior bleeding NSAID or steroid J Am Coll Cardiol. 2016;68(10):1082-1115. doi:10.1016/j.jacc.2016.03.513
Stable angina
What we must do (guidelines) 2014 ESC Guidelines 6 months 2016 ACC/AHA Guidelines 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease J Am Coll Cardiol. 2016;68(10)
What we can do (published data) 3 months (meta-analysis; n =11473)
What we will do (ongoing study) 1 month and Ticagrelor alone?
ACS
What we must do (Guidelines) 12 months STEMI et NSTEMI (ESC NSTEMI 2015)
What we can do (published studies) 3 or 6 months Randomized studies S-DAPT vs L-DAPT n % ACS Ischemic Bleeding DES LATE, NEJM 2010 2117 60% 12 Mo = >12Mo No difference EXCELLENT, JACC 2012 1443 50% 6 Mo = 12Mo No Difference PRODIGY, Circulation 2012 2013 75% 6 Mo = 24 Mo More bleeding RESET, JACC 2012 2117 55% 3 Mo = 12 Mo No difference OPTIMIZE, JAMA 2013 3119 30% 3 Mo = 12 Mo More bleeding ISAR SAFE, AHA 2014 4005 40% 6Mo = 12 Mo More Bleeding
What we will do (on going study) DAPT 3 months / Ticagrelor alone TWILIGHT STUDY High risk patient undegoing PCI with DES
High ischemic risk population
Procedural factors Ischemic Benefit of long-term DAPT according to the degree of PCI complexity Giustino et al. JACC 2016
Clinical factors High ischemic risk post MI patients PEGASUS : DAPT 12 vs 33 months * Age >65 yrs, diabetes, 2 nd prior MI, multivessel CAD, or chronic non-end stage renal dysfunction Bonaca MP. NEJM. 2015.
30 months or forever?
ACC Guideline DAPT > 1 year reasonable (IIb) in low risk bleeding patient 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease
High bleeding risk patient What we must do (Guideline) 3-6 months 2014 ESC Guidelines 2016 ACC/AHA Guideline
What we can do (published study) 1 month LEADER FREE DES (Biomatrix) vs BMS with one month DAPT In high hemorragic risk population (age> 75 ans, OAC,..) Urban, NEJM 2014
Need Help? Ischemic risk Advanced age ACS Prior MI Extensive CAD Diabetes CKD Risque TIS ACS Diabete LVEF < 40 % 1 er génération DES ISR Bifurcation Stent undersized or deployed Small diameter or long Stent? Hemorragic risk 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: Advanced age Female sex BMI <25 CKD Diabete Oral anticoagulation Anémia History of prior bleeding NSAID or steroid J Am Coll Cardiol. 2016;68(10):1082-1115. doi:10.1016/j.jacc.2016.03.513
DAPT score
PARIS score
% patients sous DAPT DAPT duration in real life From CRAC registry (2016) STEMI ST- Stable 100,0% 90,0% 80,0% 93,8% 94,6% 93,8% 87,1% 85,4% 82,2% 70,0% 60,0% 50,0% 50,2% 55,1% 54,6% 40,0% 30,0% 20,0% 10,0% 0,0% > 1 mois > 6 mois > 1 an
Conclusions The choice of DAPT duration is complex depending on many factors including initial clinical status and need a personalized evaluation for each patient of ischemic and hemorragic risk DAPT and PARIS scores could help the decision of DAPT continuation after 12 months On going studies with short DAPT and rapid switch with Ticagrelor alone could soon change the paradigm
Back up slides Specific population with AC
What we must do (Guidelines) 1 month triple therapy
What we can do (published study) Clopidogrel + AVK 12 Months Bleeding WOEST trial Post PCI SAPT + AVK vs DAPT+ AVK All Deaths Gibson
What we will do (on going study) Clopidogrel + Rivaroxaban 12 Months PIONEER study (post PCI + NVAF) Kaplan-Meier Estimates of First Occurrence Kaplan-Meier Estimates of First of Clinically AVK Significant + DAPT Bleeding vs RVX Events (10mg) + DAPT vs RVX Occurrence (15 mg) of + CV SAPT Death, MI or Stroke TIMI Major, TIMI Minor, or Bleeding Requiring Medical Attention (%) VKA VKA + DAPT + DAPT Riva + DAPT Riva + P2Y 12 v. VKA + DAPT HR=0.59 (95% CI: 0.47-0.76) p <0.000013 ARR=9.9 NNT=11 p<0.000013 p<0.00018 Riva + P2Y 12 HR = 0.63 (95% CI 0.50-0.80) HR ARR = 0.59 = (95% 8.7 Riva + CI DAPT 0.47-0.76) v. VKA + DAPT ARR NNT = 9.9 = 12HR=0.63 (95% CI: 0.50-0.80) NNT = 11 p <0.00018 ARR=8.7 NNT=12 26.7% 18.0% 16.8% Cardiovascular Death, Myocardial Infarction, or Stroke (%) VKA + DAPT Riva + P2Y 12 v. VKA + DAPT HR=1.08 (95% CI: 0.69-1.68) p=0.750 Riva + P2Y 12 Riva + DAPT Riva + DAPT v. VKA + DAPT HR=0.93 (95% CI: 0.59-1.48) p=0.765 6.5% 6.0% 5.6% No. at risk VKA Riva + DAPT P2Y 12 VKA Riva + DAPT VKA + DAPT 697 706 696 697 706 697 Days 593 636 628 555 600 606 521 579 585 461 543 426 509 510 383 329 409 593 636 555 600 521 579 461 543 426 509 409 329 593 555 521 461 426 329 Treatment-emergent period: period starting after the first study drug administration following randomization and ending 2 days after stop of study drug. Clinically significant bleeding is the composite of TIMI major, TIMI minor, and BRMA. Hazard ratios as compared to the VKA group are based on the (stratified, only for Overall, 2.5 mg BID/15 mg QD comparing VKA) Cox proportional hazards model. Log-Rank P-values as compared to VKA group are based on the (stratified, only for Overall, 2.5 mg BID/15 mg QD comparing VKA) two-sided log rank test. Gibson et al. AHA 2016 No. at risk Riva + P2Y 12 Riva + DAPT VKA + DAPT 694 704 695 648 662 635 633 640 607 621 628 579 Days 590 596 543 562 570 514 Treatment-emergent period: period starting after the first study drug administration following randomization and ending 2 days after stop of study drug. Composite of adverse CV events is composite of CV death, MI, and stroke. Hazard ratios as compared to VKA group are based on the (stratified, only for the Overall, 2.5 mg BID/15 mg QD comparing VKA) Cox proportional hazards model. Log-Rank P-values as compared to the VKA group are based on the (stratified, only for Overall, 2.5 mg BID/115 mg QD comparing VKA) two-sided log rank test. 6 Subjects were excluded from all efficacy analyses because of violations in Good Clinical Practice guidelines 430 457 408 Gibson et al. AHA 2016
Patients With Atrial Fibrillation Undergoing Coronary Stent Placement: PIONEER AF-PCI End of treatment 12 months 2100 patients with NVAF Coronary stenting No prior stroke/tia, GI bleeding, Hb<10, CrCl<30 72 hours After Sheath removal R A N D O M I Z E 1,6, or 12 months Rivaroxaban 15 mg qd* Clopidogrel 75 mg qd Pre randomization MD Choice Rivaroxaban 2.5 mg bid Clopidogrel 75 mg qd Aspirin 75-100 mg qd 1,6, or 12 months Pre randomization MD Choice VKA (target INR 2.0-3.0) Clopidogrel 75 mg qd Aspirin 75-100 mg qd Rivaroxaban 15mg QD Aspirin 75-100 mg qd VKA (target INR 2.0-3.0) Aspirin 75-100 mg qd WOEST Like ATLAS Like Triple Therapy Primary endpoint: TIMI major + minor + bleeding requiring medical attention Secondary endpoint: CV death, MI, and stroke (Ischemic, Hemorrhagic, or Uncertain Origin) *Rivaroxaban dosed at 10 mg once daily in patients with CrCl of 30 to <50 ml/min. Alternative P2Y 12 inhibitors: 10 mg once-daily prasugrel or 90 mg twice-daily ticagrelor. Low-dose aspirin (75-100 mg/d). Open label VKA Gibson et al. AHA 2016