Modern management of atrial fibrillation, from blood pressure control to anticoagulation

Transcription

1 Modern management of atrial fibrillation, from blood pressure control to anticoagulation Adel Khalifa S. Hamad, BMS, MD, FRCP(Canada) Consultant Cardiologist & Interventional Cardiac Electrophysiologist Bahrain Defence Force Hospital Kingdom of Bahrain December 6 th, 2013

2 Prevalence, % Prevalence, % Prevalence of AF stratified by age and gender European age-related prevalence US age-related prevalence (n=4053) (n=2590) (n=7995) (n=10179) Age, Yr Age, Yr Heeringa J et al. Eur Heart J 2006 Go AS et al, JAMA 2001

3 Patients with clinical parameter (%) AF-related strokes are associated with greater disability and a higher mortality rate Fatal strokes (%) Strokes with AF (N=216) Strokes without AF (N=845) Disability at clinical presentation 1 30-day post-stroke mortality 2 30 P<0.005 P< P< Severe limb weakness Bedridden 1. Dulli DA, et al. Neuroepidemiology 2003;22: Lin HJ, et al. Stroke 1996;27: Strokes with AF (N=103) Strokes without AF (N=398)

4 Limitations of VKA therapy Unpredictable response Narrow therapeutic window (INR range ) Slow onset/ offset of action VKA therapy has several limitations that make it difficult to use in practice Numerous food drug interactions Numerous drug drug interactions Warfarin resistance Routine coagulation monitoring Frequent dose adjustments Ansell J, et al. Chest 2008;133;160S-198S. Umer Ushman MH, et al. J Interv Card Electrophysiol 2008;22:

5 Eligible patients receiving Warfarin (%) INR control: Clinical trials VS. clinical practice (TTR) Clinical trial 1 Clinical practice 2,3 66% 38% 44% 25% 9% < >3.0 INR 18% AK 14/41 1. Kalra L, et al. BMJ 2000;320: ; 2. Samsa GP, et al. Arch Intern Med 2000;160:

6 Trials of new oral anticoagulants for SPAF Direct thrombin inhibitor Factor Xa inhibitors RE-LY ROCKET-AF ARISTOTLE Dabigatran ~ pts PROBE design Mean CHADS Stroke or systemic embolism Major bleeding Rivaroxaban ~ pts Double blind Mean CHADS Stroke or systemic embolism Major and nonmajor clinically relevant bleeding Apixaban ~ pts Double blind Mean CHADS Stroke or systemic embolism Major bleeding AK 18/41

7 Margin = 1.46 RE-LY primary efficacy outcome: stroke or systemic embolism Dabigatran 110 mg BID vs. warfarin Noninferiority P value <0.001 Superiority P value 0.30 Dabigatran 150 mg BID vs. warfarin <0.001 < Hazard ratio Connolly SJ et al. N Engl J Med 2009;361: ; Connolly SJ et al. N Engl J Med 2010;363: AK 20/41

8 Cumulative event rate (%) ROCKET AF primary efficacy endpoint ITT Stroke or systemic embolism HR=0.88 (0.75, 1.03) p<0.001 (non-inferiority) p=0.12 (superiority) Warfarin Rivaroxaban ITT population Days since randomization Number of subjects at risk Rivaroxaban 7,081 6,879 6,683 6,470 5,264 4,105 2,951 1,785 Warfarin 7,090 6,871 6,656 6,440 5,225 4,087 2,944 1,783 AK 26/41 Patel MR et al. N Engl J Med 2011;365:

9 Percent with event ARISTOTLE Primary Efficacy Outcome Stroke or Systemic Embolism 4 3 p (non-inferiority) <0.001 p (superiority) = Warfarin 21% RRR 2 Apixaban 1 0 HR 0.79 (95% CI, 0.66, 0.95) Months AK 31/41 Granger CB, et al. N Engl J Med. 2011;365:

10 LAA Occlusion procedures Surgical Percutaneous PLAATO system WATCHMAN device Amplatzer cardiac plug LARIAT system AK 1/41

11 Event-free probability PROTECT AF: Intent-to-Treat Primary Safety Results Randomization allocation (2 device : 1 control) Device Control Events Total Rate Events Total Rate Rel. Risk Cohort (no.) pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI) 900 pt-yr (6.4, 11.3) (2.2, 6.7) (1.18, 4.13) WATCHMAN ,095 Days Control ITT Cohort: patients analyzed based on their randomly assigned group (regardless of treatment received)

12 Event-free probability PROTECT AF: Intent-to-Treat Primary Efficacy Results Randomization allocation (2 device : 1 control) Device Control Posterior Probabilities Events Total Rate Events Total Rate Rel. Risk Non- Cohort (no.) pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI) inferiority Superiority 900 pt-yr (2.1, 5.2) (2.8, 7.6) (0.37, 1.41) ,095 Days WATCHMAN Control ITT Cohort: patients analyzed based on their randomly assigned group (regardless of treatment received)

13 Mortality (%) AFFIRM: Mortality with rate and rhythm control strategies HR = % CI: P = 0.08 Rhythm-control Rate-control Years AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management Wyse DG et al. N Engl J Med 2002;347: AK 1/41

14 Incidence (%) AFFIRM: Stroke incidence with rate and rhythm control strategies 10 Rhythm-control P = P = 0.79 Rate-control P = 0.73 P = Ischaemic stroke Intracerebral haemorrhage Subdural/ subarachnoid haemorrhage All CNS events Wyse DG et al. N Engl J Med 2002

15 ATHENA study: Maintenance of sinus rhythm with dronedarone delays hospitalization for CV causes or death Cumulative incidence, % Hospitalization due to CV events or death from any cause P<0.001 Placebo Dronedarone n = Years Hohnloser SH et al. N Engl J Med 2009

16 Technique of AF ablation Ablation of triggering focus Circumferential PV isolation

17 MANTRA-PAF Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation Cosedis Nielsen J et al, N Engl J Med 2012

18 MANTRA-PAF Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation Quality of Life Scores Cosedis Nielsen J et al, N Engl J Med 2012