The Challenge. Warfarin or Novel Oral Anti-Coagulants in the PCI patient? Anticoagulation/Stroke

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1 Anticoagulation/Stroke Warfarin v new oral anticoagulants post PCI Warfarin or Novel Oral Anti-Coagulants in the PCI patient? Gerry Devlin Chairs: Phillip Matsis & Tony Scott Gerry Devlin Honorary Associate Professor University of Auckland Cardiologist Waikato Hospital Warfarin or Novel Oral Anti-Coagulants in the PCI patient (with AF)? Gerry Devlin Honorary Associate Professor University of Auckland Cardiologist Waikato Hospital Atrial fibrillation in New Zealand primary care: Prevalence, risk factors for stroke and the management of thromboembolic risk. retrospective cohort study utilising electronic medical records for 739,000 patients registered with 170 general practices in Prevalence 1.7% (12,712) significantly higher for Maori (odds ratio 1.91, 95% confidence interval ) Tomlin,Lloyd and Tilyard :Eur J Prev Cardiol Feb;24(3): The Challenge Up to 30% patients with AF have co-existing IHD 5-10% will require PCI Oral anticoagulation with either vitamin K antagonists or non-vka oral anticoagulants is the mainstay for prevention of thrombo-embolic events in AF DAPT necessary to reduce cardiac events (including ST) 1

2 Eddie:78 year old man with ACS CABG 2004 (Lima to LAD,SVG to PDA,SVG to OM) CVA 3/12 previous R Carotid Endarterectomy post CVA AF ( Dabigatran 150mg BD) PVD Mild renal impairment (Creat 112mmol/l,eGFR 45ml/min/m2) Hx Achohol abuse POST ASPIRATION THROMBECTOMY Eddie:Discharge Rx Dabigatran 150mg BD Aspirin 100 mg /day Ticagrelor 90mg BD KEY CONSIDERATIONS Stent Type Clinical presentation Can we omit OAC or Aspirin? Duration of DAPT NOAC v Warfarin Which P2Y12 Inhibitor 2

3 Eddie:10/7 later Malaena OGD: Large Bleeding Gastric Ulcer Omeprazole 40 mg BD 3

4 Cumulative incidence (%) Cumulative incidence (%) 21/06/ Should this Surprise Us? CHADS-2 VASC 4 Stroke risk 8.5%/yr HAS BLED 5 Bleeding Risk 12.8%/yr 22 RCTs of OACs following PCI WOEST: exclusion of ASA from combination therapy is associated with improved outcomes vs triple therapy Number at risk Triple therapy Double therapy Total number of TIMI bleeding events Triple-therapy group Double-therapy group Time (days) OAC + clopidogrel associated with significant reduction in major bleeding and no increase in thrombotic events vs triple therapy with OAC + clopidogrel + ASA 573 patients receiving OAC and undergoing PCI in open-label, randomized WOEST trial TVR, target vessel revascularisation; ST, stent thrombosis; TIMI, thrombolysis in myocardial infarction bleeding criteria Dewilde WJ et al. Lancet 2013;381: % 19.4% HR: 0.36 (95% CI: ) P< Death, MI, TVR, stroke, ST Triple-therapy group Double-therapy group HR: 0.60 (95% CI: ) P= % 11.1% Time (days) ISAR-TRIPLE Trial design: 614 Patients with an indication for oral anticoagulation (OAC) and undergoing DES PCI were randomized to either 6 weeks or 6 months of triple therapy (aspirin + clopidogrel + OAC initially, aspirin + OAC indefinitely). Patients were followed for 9 months. Results (p = 0.63) Primary endpoint: Composite of death, MI, stent 20 thrombosis, stroke, TIMI major bleeding at 9 months for 6 weeks vs. 6 months of triple therapy: 9.8% vs. 8.8%, HR 1.14, 95% CI , p = 0.63 Cardiac death, MI, stent thrombosis, ischemic stroke: % vs. 4.3%, p = 0.87; TIMI major bleeding: 5.3% % vs. 4.0%, p = 0.44 Stent thrombosis: 0.7% vs. 0% Conclusions 6-week duration of triple therapy is not superior 0 to a 6-month duration of triple therapy in patients undergoing DES PCI, who also had an Primary endpoint at 9 months indication for OAC use 6-week triple 6-month Trial was underpowered to assess smaller therapy triple therapy bleeding differences (n = 307) (n = 307) J Am Coll Cardiol. 2015;65(16): doi: /j.jacc

5 PIONEER AF-PCI Trial design: Patients with AF and PCI randomized to: Group 1: Rivaroxaban 15 mg daily plus P2Y12 inhibitor for 12 months (n = 709). Group 2: Rivaroxaban 2.5 mg twice daily plus DAPT for 1-12 months (n = 709). Group 3: warfarin plus DAPT for 1-12 months (n = 706). (p < for group Results 1 or 2 vs. group 3) Primary EP: Clinically significant bleeding at 12 months: 16.8% in group 1 vs. 18.0% in 26. group 2 vs. 26.7% in group 3 (HR 0.59, p < for group 1 vs. 3); (HR 0.63, p < % for group 2 vs. 3) Stent thrombosis: 0.8% in group 1 vs. 0.9% in group 2 vs. 0.7% in group 3 (HR 1.20, p = 0.79 for group 1 vs. 3; HR 1.44, p = 0.57 for group 2 vs. 3) Conclusions Among patients with nonvalvular AF who underwent PCI, a rivaroxabanbased strategy was associated with a Rivaroxaban 15 mg daily, P2Y12 for 12 months lower frequency of clinically significant Rivaroxaban 2.5 mg daily, DAPT for 1-12 months bleeding compared with a warfarin/dapt strategy Warfarin, DAPT for 1-12 months Stent thrombosis appeared to be similar between the three groups Gibson CM, et al. N Engl J Med 2016;375: RE-DUAL PCI Cannon CP, et al. N Engl J Med 2017;Aug 27:[Epub] Conclusion: Dabigatran + single anti-platelet agent compared with triple therapy was effective at reducing bleeding events with no increase ischaemic events A systematic review and metaanalysis for Phase 3, randomized trials that compared DAT vs. TAT in patients with AF following PCI. Four trials including 5317 patients were included, of whom 3039 (57%) received DAT. 47% reduction TIMI Major/Minor Bleeding with DAT All Cause Mortality and Cardiac Death similar No increase MACE with DAT 5

6 MI and Stent Thrombosis similar Stroke similar DAT reduces bleeding with no increase MACE Careful assessment of the bleeding and ischaemic risks (i.e. stroke, new or recurrent cardiac ischaemia or infarction, and stent thrombosis) should be undertaken for patients with AF who have a long-term requirement for anticoagulation for stroke prevention and require dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) or stent implantation (or both). (GRADE quality of evidence: Low; GRADE strength of recommendation: Strong) Where DAPT is required in combination with OAC, low-dose aspirin (100 mg) and clopidogrel (75 mg) are recommended Ticagrelor and prasugrel are not recommended in this situation. NOACs can be used with DAPT in eligible patients; if NOACs are used, the lowest dose proven to be effective for stroke prevention is recommended. (GRADE quality of evidence: Low; GRADE strength of recommendation: Strong) (GRADE quality of evidence: Moderate; GRADE strength of recommendation: Weak) 6

7 Combining anticoagulation (warfarin, dabigatran and rivaroxaban) with a single antiplatelet agent (clopidogrel or ticagrelor) can be considered post-stenting If triple therapy (aspirin, P2Y12 inhibitor and OAC) is selected, duration should be for at least a month after stenting or ACS (or both), with the duration extended to six months in patients at low risk of bleeding. (GRADE quality of evidence: Moderate; GRADE strength of recommendation: Weak) (GRADE quality of evidence: Moderate; GRADE strength of recommendation: Strong) Where OAC is used for AF, discontinuation of antiplatelet therapy should be considered 12 months after stent implantation, with continuation of OAC alone. (GRADE quality of evidence: Low; GRADE strength of recommendation: Weak) What remains unknown Are the doses of rivaroxaban used in PIONEER AF-PCI (i.e. 2.5 mg BID or 15 mg OD) sufficient for stroke prevention? Are dual therapy strategies combining a NOAC with clopidogrel safer in terms of bleeding risk than a dual therapy with a VKA and clopidogrel? Does dual therapy (i.e. rivaroxaban 15 mg OD or dabigatran 110/150 mg BID in combination with a P2Y12 inhibitor) sufficiently protects against stent thrombosis or myocardial infarction? Is dual therapy with NOAC (or VKA) and aspirin an alternative to NOAC and a P2Y12 inhibitor? What about ticagrelor and prasugrel in dual or triple therapy regimens? 7

8 Eddie and what we would perhaps do differently in Dabigatran 110 mg BD Clopidogrel 75mg/day x 12/12 minimum Cartia 100 mg/day x 3/12 Thank You Omeprazole 40 mg/day 8