Novità in Tema di NOACs Cardioversione Riccardo Cappato, MD

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1 Novità in Tema di NOACs Cardioversione Riccardo Cappato, MD Electrophysiology & Arrhythmia Center IRCCS Humanitas Research Institute, Milan & Gavazzeni Clinics, Bergamo - Italy

2 Disclosure Statement of Financial Interest Consultant to: Boston Scientific; Medtronic; St. Jude; Biosense Webster; ELA Sorin; Boehringer Ingelheim; Bayer HealthCare; Abbott; Pfizer; Daiichi-Sankyo Speaker s Bureau: Boston Scientific; Medtronic; St. Jude; Biosense Webster; BARD; Sanofi; Boehringer Ingelheim; Bayer HealthCare; Abbott Investigator: Medtronic; Biosense Webster; Sanofi; Cameron Health, BARD; Bayer HealthCare; Abbott; Pfizer Grants: Boston Scientific; Medtronic; St. Jude; Biosense Webster; BARD; ELA Sorin Equity and Intellectual Property Rights: Cameron Health

3 ACUTE Study Assessment of Cardioversion Using TEE Primary outcome: composite of cerebrovascular accident, TIA, peripheral embolism Secondary outcomes: bleeding, death, success of cardioversion, functional status Klein A et al. 2001

4 RE-LY: Outcomes after Cardioversion This post-hoc subgroup analysis showed: 1983 cardioversions performed in 1270 patients, not including ablation Stroke/systemic embolism rates in the 30 days following cardioversion were low and similar for both doses of dabigatran and warfarin group, with or without TEE Groups Dabigatran 110mg BID Dabigatran 150mg BID Warfarin P value Cardioversions Electrical cardioversion 85.60% 81.90% 83.30% TEE before cardioversion 25.50% 24.10% 13.30% LA Thrombus Positive 1.80% 1.20% 1.10% On study drug 3 weeks before cardioversion 76.40% 79.20% 85.50% < 0.01 for both Stroke and systemic embolism 0.77% 0.30% 0.60% NS for both Major bleeding 1.70%* 0.60%** 0.60% *0.06, **0.99 Nagarakanti et al, 2011

5 Cardioversion in ROCKET AF Total 350 procedures performed, including surgical or catheter ablation, electrical and pharmacological cardioversion * On study drug 21 days after procedure Cardioversion in ROCKET AF During Treatment Period Safety Analysis Set Safety on-treatment Set* Groups Warfarin Warfarin All Cardioversions Primary Efficacy Endpoint 0.56% 0.58% Secondary endpoint % 1.16% Secondary endpoint % 2.31% 0.79% 0 Principal Safety Endpoint 2.26% 8.09% 0.79% 7.58% Major bleeding 0.56% 2.31% % Endpoint 1: composite of stroke, systemic embolism, CV death Endpoint 2: composite of stroke, systemic embolism, CV death, MI

6 Cardioversion in ARISTOTLE Results Flaker et al, 2013

7 NOACs for Naïve Patients for Cardioversion

8 Cardioversion Cardioversion End of study treatment X-VeRT: Study design Inclusion criteria: Age 18 years, non-valvular AF lasting >48 h or unknown duration, scheduled for cardioversion Cardioversion strategy Early (only if adequate anticoagulation or immediate TEE) R 2:1 20 mg od* 1 5 days 20 mg od* 20 mg od* 42 days 20 mg od* OAC 30-day follow-up Delayed R 2:1 21 days (max. 56 days) 42 days *15 mg if CrCl ml/min; with INR Cappato et al, 2014

9 X-VeRT: Primary Efficacy Outcome (N=978) (N=492) % n* % n* Risk ratio (95% CI) Primary efficacy outcome ( ) Stroke Haemorrhagic stroke Ischaemic stroke TIA Non-CNS SE MI Cardiovascular death *Number of patients with events; patients may have experienced more than one primary efficacy event mitt population Cappato et al, 2014

10 Days Patients (%) Time to Cardioversion by Cardioversion Strategy Median time to cardioversion Patients cardioverted as scheduled* p=0.628 Early p< day s 30 day s Delayed ,0 p< patient with inadequate anticoagulation 36,3 95 patients with inadequate anticoagulation Delayed group *Reason for not performing cardioversion as first scheduled from days primarily due to inadequate anticoagulation (indicated by drug compliance <80% for rivaroxaban or weekly INRs outside the range of for 3 consecutive weeks before cardioversion for ) Cappato et al, 2014

11 Comparing Novel OACs and Warfarin in AF Patients Undergoing Cardioversion Stroke/SE NOAC Warfarin Odds ratio Odds ratio Study or subgroup Event Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI ARISTOTLE Not estimable RE-LY % 0.88 ( ) ROCKET AF % 0.99 ( ) X-VeRT % 0.33 ( ) Total (95% CI) % 0.73 ( ) Total events Heterogeneity: Tau 2 =0.00; Chi 2 =0.96; df=2 (p=0.62); I 2 =0% Test for overall effect: Z=0.72 (p=0.47) Major bleeding or clinically relevant non-major bleeding ARISTOTLE % 1.25 ( ) RE-LY % 1.90 ( ) ROCKET AF % 1.49 ( ) X-VeRT % 0.76 ( ) Total (95% CI) % 1.41 ( ) Total events Heterogeneity: Tau 2 =0.00; Chi 2 =1.25; df=3 (p=0.74); I 2 =0% Test for overall effect: Z=1.40 (p=0.16) Stroke/SE: TEE prior to cardioversion ARISTOTLE Not estimable RE-LY % 0.26 ( ) X-VeRT % 0.11 ( ) Total (95% CI) % 0.17 ( ) Total events 1 3 Heterogeneity: Tau 2 =0.00; Chi 2 =0.20; df=1 (p=0.66); I 2 =0% Test for overall effect: Z=1.67 (p=0.09) Favours NOAC Favours warfarin Cardioversion: electrical or pharmacological Sen P et al. Am J Cardiovasc Drugs 2015; doi: /s

12 NOACs for Cardioversion of AF Conclusions In patients under chronic treatment with NOACs who require cardioversion, the peri-procedural incidence of TE and bleeding events is low and similar to what expected under therapy In patients naïve to NOACs undergoing elective cardioversion, use of rivaroxaban is associated with a peri-procedural incidence of TE and bleeding events which is low and similar to what expected under therapy