GRAND ROUNDS - DILEMMAS IN ANTICOAGULATION AND ANTIPLATELET THERAPY. Nick Collins February 2017

Transcription

1 GRAND ROUNDS - DILEMMAS IN ANTICOAGULATION AND ANTIPLATELET THERAPY Nick Collins February 2017

2 DISCLOSURES Before I commence Acknowledge.. Interventional Cardiologist Perception evolved. Interventional Cardiologists Orthopaedic surgeons Everyone Else.

3 BACKGROUND Perception Stent first.. Questions later Oculo-stenotic reflex Percutaneous coronary intervention (PCI) Need for dual anti-platelet therapy (DAPT) Focus on clopidogrel in addition to aspirin Abundantly clear. Need for DAPT interruption Surgery Bleeding Co-existing need for systemic anticoagulation Particular reference atrial fibrillation

4 BACKGROUND Case Presentation Highlight Common Increasingly problematic Cardiac electrophysiology Information to guide therapy - limited Illustrate ACC Sub-Specialty guidelines Randomised data Clinician assessment/judgement Common strategies similarly limited

5 EB 74 YEAR OLD FEMALE Illustrate difficulties Research Not comprehensive analysis. Discussion

6 BACKGROUND Known IHD Presented 1995 Balloon angioplasty RCA Further acute presentation Feb 1996 PCI Bare metal stent (BMS) Subacute stent thrombosis March 1996 Unsuccessful attempt PCI CABG May 1996 Radial artery graft to distal RCA Repeat presentation Occluded graft CABG Nov 1996 RIMA to RCA

7 PROGRESS Paroxysmal atrial fibrillation 2012 Self resolved Review discharge summary CHADS2 1 Unclear Not anticoagulated at that stage 2014 Sotalol Warfarin

8 ONGOING SAGA. Presented 2015 Rest angina Lateral ST depression Troponin rise Preserved left ventricular systolic function Repeat angiography

9

10

11

12

13 OPTIONS? Audience Medical therapy Bare metal stent (BMS) Drug eluting stent (DES) CABG (#3) LIMA Saphenous vein graft LAA Closure AF ablation

14 USUAL APPROACH PCI Stent insertion Limitations repeat CABG Favour DES as opposed to BMS Pause In the dark.literally and figuratively Advantage Disadvantage New generation devices Overcome issue prolonged DAPT DAPT mandatory duration differs

15 IF PROCEEDING TO PCI.. Approach to antiplatelet therapy and anticoagulation Triple therapy vs double therapy (omit aspirin) Duration Warfarin vs NOAC Adjust intensity Lower dose NOAC (eg apixaban 2.5mg bd) Incorporate newer, more potent antiplatelet therapies into regimen So much uncertainty Risk scores to guide us! Thrombotic risk Bleeding risk

16 AF RISK SCORES Various regimens Higher risk Age > 65 years Incremental risk Hypertension CCF Diabetes mellitus Vascular disease Previous stroke

17 BLEEDING BAD HAS-BLED Hypertension Abnormal liver/renal function Stroke Bleeding Labile INR Elderly (>65 years) Drugs (aspirin, NSAIDS) or alcohol Illustrate limitations Those at highest risk thrombotic complications highest risk bleeding.

18 NEXT STEP. Guidelines Professional societies ACC Interventional Clopidogrel and warfarin Electrophysiology Triple therapy

19 WOEST What is the Optimal antiplatelet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing trial 573 patients 70% AF Randomised Triple therapy vs double therapy Primary end point Cumulative incidence all TIMI bleeding Divided Major/minor/minimal

20 WOEST: PRIMARY END POINT ALL BLEEDING EVENTS (TIMI CRITERIA) Dual therapy (%) Triple therapy (%) p<0.001 Type of bleeding Dual therapy (%) Triple therapy (%) TIMI minimal TIMI minor TIMI major

21 FURTHERMORE Lower rate blood transfusion MACCE Composite Death/MI/Stroke/Systemic embolisation/tvr/stent thrombosis Ie not just bleeding end point Interpretation.

22 LIMITATIONS AF in 70% 573 patients only Power insufficient for secondary end points No difference in major bleeding Relevant Minor bleeding = discontinuation clopidogrel Low absolute number major bleeding events 16 vs 9!

23 IF I MAY CONTINUE Bare metal stent 31% Short DAPT Contemporary practice Argue disconnect Radial access 26% Low PPI use 37% Guidelines.. INR 2-3 Not reduced to as recommended by guidelines

24 BACK TO OUR PATIENT - INITIAL APPROACH Consult widely. Medical therapy Naturally Failed Represented

25

26 PCI LAD Successful PCI Orsiro DES Committed Aspirin and clopidogrel ACTIVE series Oral anticoagulation

27 NO OPTIMAL APPROACH. Enrolled in PIONEER Rivaroxaban/Clopidogrel Plan for 6 months in keeping trial design

28 Gibson et al. AHA 2016

29 Baseline Characteristics Riva + P2Y 12 (N=709) Riva + DAPT (N=709) VKA + DAPT (N=706) Age, mean ± SD 70.4 ± ± ± 8.7 Sex, female, n (%) 181 (25.5%) 174 (24.5%) 188 (26.6%) Diabetes Mellitus, n (%) 204 (28.8%) 199 (28.1%) 221 (31.1%) Type of Index Event, n (%) NSTEMI 130 (18.5%) 129 (18.4%) 123 (17.8%) STEMI 86 (12.3%) 97 (13.8%) 74 (10.7%) Unstable Angina 145 (20.7%) 148 (21.1%) 164 (23.7%) Stable Angina 340 (48.5%) 329 (46.8%) 330 (47.8%) Drug-eluting stent, n (%) 464 (65.4%) 471 (66.8%) 468 (66.5%) Type of Atrial Fibrillation, n (%) Persistent 146 (20.6%) 146 (20.6%) 149 (21.1%) Permanent 262 (37.0%) 238 (33.6%) 243 (34.5%) Paroxysmal 300 (42.4%) 325 (45.8%) 313 (44.4%) Gibson et al. AHA 2016

30 TIMI Major, TIMI Minor, or Bleeding Requiring Medical Attention (%) Kaplan-Meier Estimates of First Occurrence of Clinically Significant Bleeding Events 26.7% VKA VKA + DAPT + DAPT Riva + DAPT p< p< % 16.8% Riva + P2Y 12 v. VKA + DAPT HR=0.59 (95% CI: ) p < ARR=9.9 NNT=11 Riva + P2Y 12 HR = 0.63 (95% CI ) HR ARR = 0.59 = (95% 8.7 Riva + CI DAPT ) v. VKA + DAPT ARR NNT = 9.9 = 12HR=0.63 (95% CI: ) NNT = 11 p < ARR=8.7 NNT=12 No. at risk VKA Riva + DAPT P2Y 12 VKA Riva + DAPT VKA + DAPT Days 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

31 Cardiovascular Death, Myocardial Infarction, or Stroke (%) Kaplan-Meier Estimates of First Occurrence of CV Death, MI or Stroke Riva + P2Y % 6.0% 5.6% Riva + DAPT VKA + DAPT Riva + P2Y 12 v. VKA + DAPT HR=1.08 (95% CI: ) p=0.750 Riva + DAPT v. VKA + DAPT HR=0.93 (95% CI: ) p=0.765 No. at risk Riva + P2Y 12 Riva + DAPT VKA + DAPT Days 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 Gibson et al. AHA 2016

32 All Cause Rehospitalization (%) All Cause Hospitalization for an Adverse Event 41.5% VKA + DAPT Riva + P2Y 12 Riva + DAPT 34.1% 31.2% Riva + P2Y 12 v. VKA + DAPT HR=0.77 (95% CI: ) p=0.005 ARR=7.4 NNT=14 Riva + DAPT v. VKA + DAPT HR=0.74 (95% CI: ) p=0.001 ARR=10.3 NNT=10 No. at risk Riva + P2Y 12 Riva + DAPT VKA + DAPT Days Treatment-emergent period: period starting after the first study drug administration following randomization and ending 2 days after stop of study drug. Rehospitalizations do not include the index event and include the first rehospitalization after the index event. Hazard ratios as compared to the VKA group are based on the Cox proportional hazards model. Log-Rank P-values as compared to VKA group are based on the two-sided log rank test Gibson et al. AHA 2016

33 CONCLUSION Among stented AF participants, administration of either rivaroxaban 15 mg daily plus P2Y 12 monotherapy for one year or rivaroxaban 2.5 mg BID plus 1, 6, or 12 months of DAPT reduced the risk of clinically significant bleeding as compared with standard of care VKA plus 1, 6, or 12 months of DAPT and yielded comparable efficacy with broad confidence intervals 9.0 Gibson et al. AHA 2016

34 PROGRESS Represented 10 days later Atrial fibrillation Rapid ventricular response Symptomatic Anticoagulation interrupted Standard to hold anticoagulation therapy Avoid peri-procedural bleeding Radial vs femoral No guarantees

35 APPROACH Symptomatic AF Uncertainty regarding anticoagulation Rate control Chemical cardioversion Electrical cardioversion Transoesophageal echocardiography

36

37 OPTIONS Time Dose rivaroxaban Change oral anticoagulation Remove from trial Defer DC cardioversion Rate control Warfarin Repeat TOE

38 SUMMARISE Complex area Each year. Data limited Guidelines are less than ideal Data still emerging Complex study design limits interpretation/generalisability Available dosing. Increasingly common 10% > 80 years Remain role for clinical acumen