Triple Therapy After PCI in AF: A Quagmire Soon to be Drained Freek W.A. Verheugt Department of Cardiology, Onze Lieve Vrouwe Gasthuis (OLVG) Amsterdam, Netherlands
D ISCLOSURES FOR F REEK W. A. V ERHEUGT Research support/ Bayer HealthCare, Boehringer Ingelheim, principal investigator Eli Lilly and Roche Bayer Healthcare, Eli Lilly, Daiichi-Sankyo, Consultant and Merck Speakers’ bureau none Bayer Healthcare, Eli Lilly, Daiichi-Sankyo and Honoraria Merck Scientific advisory board AstraZeneca and Cardialysis B.V.
Triple Therapy in Stented Patients Benefit and risk in registries Benefit and risk in randomized controlled trials Guidelines Future perspectives
Triple Therapy in Stented Patients Benefit and risk in registries Benefit and risk in randomized controlled trials Guidelines Future perspectives
Risk of Triple Therapy on Bleeding in 82,854 Danish AF Patients (15%) Hansen ML. Arch Intern Med. 2010;170:1433-1441
Benefit of Triple Therapy on Stroke in 82,854 Danish AF Patients Hansen ML. Arch Intern Med 2010;170:1433-1441
40,812 MI patients in Denmark with a follow-up of 16 months Sorensen R. Lancet 2009; 374: 1967 – 1974
Bleeding in Stable Coronary Disease: CORONOR Registy Hamon M. J Am Coll Cardiol 2014;64:1430-1436
Ischemic Endpoints in Stable Coronary Disease: CORONOR Registy Hamon M. J Am Coll Cardiol 2014;64:1430-1436
Dual vs Triple Therapy after Stenting in AF (n = 67) (n = 162) (n = 679) Rubboli A. Clin Cardiol 2014;37:357-364
A SPIRIN U SE IN ORBIT-AF Steinberg BA. Circulation 2013;128:721-728
Triple Therapy in Stented Patients Benefit and risk in registries Benefit and risk in randomized controlled trials Guidelines Future perspectives
Triple Therapy in AF and PCI for 6 wks vs 6 mos: ISAR-TRIPLE J Am Coll Cardiol 2015;65:1619 – 1629
Triple Therapy in AF and PCI for 6 wks vs 6 mos: ISAR-TRIPLE J Am Coll Cardiol 2015;65:1619 – 1629
WOEST Lancet 2013:381:1107-1115 Primary Endpoint: Total number of bleeding events Triple therapy group 50 % 44.9% Double therapy group Cumulative incidence of bleeding 40 % 30 % 19.5% 20 % p<0.001 10 % HR=0.36 95%CI[0.26-0.50] NNT = 4 0 % 0 30 60 90 120 180 270 365 Days n at risk: 284 210 194 186 181 173 159 140 279 253 244 241 241 236 226 208 |
WOEST Lancet 2013:381:1107-1115 Locations of TIMI bleeding: Worst bleeding per patient p<0.001 48 50 Double therapy 45 group 40 p<0.001 35 30 Triple therapy p<0.001 30 group 25 `p = NS (n=) 25 20 20 20 16 15 8 7 10 `p = NS 3 3 5 Lancet 2013:381:1107-1115 0 Intra- Acces GI Skin Other Cranial site
WOEST Lancet 2013:381:1107-1115 Secondary Endpoint 9 p=0.876 Double 8 7.3 therapy group p=0.027 6.8 7 6.4 Triple therapy 6 p=0.382 group 4.7 5 4 p=0.165 p=0.128 3.3 3.2 2.9 2.6 3 2 1.5 1.1 1 0 Lancet 2013:381:1107-1115 Death MI TVR Stroke ST MI=any myocardial infarction; TVR= target vessel revascularisation (PCI + CABG); ST= stent thrombosis
D UAL VS T RIPLE T HERAPY IN AF AFTER PCI FOR MI n= 12,165 Lamberts M. J Am Coll Cardiol 2013;62:981-989
Triple therapy in Stented Patients Benefit and risk in registries Benefit and risk in randomized controlled trials Guidelines Future perspectives
Dual Therapy in AF and PCI ACC/AHA Guidelines on AF. Circulation 2014;130:2071-2104
Global Consensus: Antithrombotic Therapy for PCI in Patients with AF and Stable CAD CHA 2 DS 2 - VASc ≥2 CHA 2 DS 2 -VASc = 1 STEP 1: stroke risk Low to intermediate High Low to intermediate High STEP 2: bleeding risk (e.g. HAS-BLED = 0 – 2) (e.g. HAS- BLED ≥3) (e.g. HAS-BLED = 0 – 2) (e.g. HAS- BLED ≥3) Triple or dual Triple or dual therapy therapy O A C O A C Triple or dual 4 weeks Dual therapy therapy or O C O A C DAPT A C or STEP 3: antithrombotic DAPT Dual therapy therapy 6 months Dual therapy A C O A or C O A or C Dual therapy or O A or C DAPT A C 12 months Monotherapy ‡ O Monotherapy ‡ O Lifelong Time from PCI/ACS ASA 75 – 100 mg daily OAC Clopidogrel 75 mg daily O A C Lip GHY. Eur Heart J 2014;35:3155-3179 ESC Guidelines Revascularisation. Eur Heart J 2014;35:2541-2619
Antithrombotic Therapy in Patients with AF and ACS ESC Guidelines on NSTE-ACS. Eur Heart J 2016;37:267-315
Triple Therapy in Stented Patients Benefit and risk in registries Benefit and risk in randomized controlled trials Guidelines Future perspectives
Prospective trials of NOACs in NVAF patients with concomitant ACS or undergoing PCI are ongoing PIONEER AF-PCI (rivaroxaban) RE-DUAL PCI (dabigatran) AUGUSTUS (apixaban) 2,100 NVAF patients with PCI 2,500 NVAF patients with ACS or PCI 4,600 NVAF patients with ACS or PCI + ASA Rivaroxaban 15 mg OD* Dabigatran 150 mg BD + Apixaban R + P2Y12 inhibitor clopidogrel/ticagrelor 5 mg BD † + P2Y12 ASA + R for all inhibitor Rivaroxaban 2.5 Rivaroxaban placebo on day Dabigatran 110 mg BD + mg BD + DAPT 15 mg OD R of R clopidogrel/ticagrelor (P2Y12 inh. + ASA) + ASA + ASA ACS/P VKA (for 1, 6 or 12 CI R + P2Y12 months) inhibitor VKA + VKA + + placebo VKA + DAPT VKA clopidogrel/tic clopidogrel/ (for 1, 6 or 12 + ASA 6-month treatment agrelor + ASA ticagrelor months) period (for 1-3 m) # (ASA given double- Open-label treatment period for 12-month open-label blinded) up to 30m treatment period †Apixaban 2.5 mg BD in selected patients. # ASA will be given for 1 month post-BMS and 3 *Rivaroxaban 10 mg OD in patients with CrCl 30-50 months post-DES ml/min Primary objective: To show non-inferiority of Primary objective: To show non- Primary objective: To assess the safety of apixaban vs VKA in patients with concomitant two rivaroxaban treatment strategies vs the inferiority of two different doses of P2Y12 inhibitor therapy and To show dabigatran (150mg BD and 110 mg BD) + combination of VKA with DAPT superiority of anticoagulant (VKA or apixaban) single antiplatelet therapy (clopidogrel or Primary endpoint: TIMI major, minor plus single antiplatelet therapy (P2Y12 bleeding or bleeding requiring medical ticagrelor) vs the combination of warfarin inhibitor) vs anticoagulant plus DAPT (P2Y12 + DAPT attention (through 12 months) inhibitor + ASA) Primary endpoint: ISTH m ajor bleeding Primary endpoint: major/clinically relevant (even-driven) 1. Gibson et al. Am Heart J. 2015;169:472-478.e5; 2. Clinicaltrials.gov bleeding identifier: NCT02164864; 3. RE-DUAL PCI. (through 6 months) http://www.hcri.harvard.edu/research/trials/re-dual_pci; 4. Clinicaltrials.gov identifier: NCT02415400.
Triple Therapy in Stented Patients Take Home Messages 1. Triple therapy (OAC, clopidogrel and aspirin) for PCI in AF leads to unacceptable bleeding. Possibly, aspirin may be skipped 2. The most recent guidelines mandate for most AF patients undergoing PCI triple therapy for the shortest period as clinically acceptable. 3. For AF patients undergoing PCI the NOACs seem preferable because of their safety profile, but randomized trial data are necessary to support this
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