A focus on atrial fibrillation

Transcription

1 A focus on atrial fibrillation Is being female really a risk factor for stroke? Dr Justin Mariani MBBS BMedSci PhD FRACP FCSANZ Consultant Cardiologist and Interventional Heart Failure Specialist Alfred Hospital and St Vincent s Hospital Melbourne St Vincent s Private, Reservoir Private and Bairnsdale Hospital jmcardiology@me.com Atrial fibrillation 1. Atrial fibrillation overview 2. Gender differences they do exist 3. Current concepts in atrial fibrillation 1. Novel oral anticoagulants 2. Catheter ablation Atrial Fibrillation Three Ps Classification of Atrial Fibrillation Questioning the confirmed or probable AF patient Paroxysmal Persistent Permanent Terminates Spontaneously (usually < 48 hours) Will not terminate spontaneously; usually > 7 days; will require DCR or AAD Will not terminate spontaneously; refractory to cardioversion Question caffeine intake also Consider lone atrial fibrillation low risk Clinical outcomes impacted by AF Stroke Is The Leading Complication Of Atrial Fibrillation AF is associated with a 5-fold higher stroke risk overall 1 AF doubles the risk of stroke when adjusted for other risk factors 2 AF is responsible for nearly a third of all strokes, 3 and the leading cause of embolic stroke 4 Without prevention, approximately 1 in 20 patients will have a stroke each year 5 Approximately 1 in 3 people with a first-time stroke will die within the first 12 months 6 1. Savelieva I et al. Ann Med 2007; 39: ACC/AHA/HRS focused update guidelines: Fuster V et al. Circulation 2011; 123: e Hannon N et al. Cerebrovasc Dis 2010; 29: Emmerich J et al. Eur Heart J 2005; 7(Suppl C): C Atrial Fibrillation Investigators. Arch Intern Med 1994; 154: Thrift et al. Stroke 2000; 31:

2 Management of the AF patient Anticoagulation Is Complicated AF is a complex disease, with a diverse patient group 1 In particular, there is a need to balance stroke and bleeding risk for each individual patient 1,2 All patients should have a transthoracic echocardiogram - Atrial size; valve disease; septal defects; evidence of hypertensive heart disease; LV function 1. Padanilam BJ and Prystowsky EN. Cardiol Clin 2009; 27: Camm AJ et al. Eur Heart J 2012; 33: ESC 2012 Guidelines on Anticoagulation in AF NVAF + any risk factor = anticoagulant 1. Camm AJ et al. Eur Heart J 2012; 33: Risk assessment and flowchart for use of oral anticoagulants Gender Differences In all age groups, men have a higher incidence of atrial fibrillation than women. However, because the incidence of atrial fibrillation increases dramatically with age and because there are more women in the population older than the age of 75 years, the absolute number of women and men with atrial fibrillation in this age group is equal In general, women present at an age approximately five years older than men. This difference is analogous to the later presentation of coronary artery disease in women. Women are more symptomatic than men, possibly because of faster heart rates and small body habitus. Women experience a significantly increased frequency of symptomatic recurrences, although there was no difference in electrocardiographically documented occurrences SRAF Working Group, Neurology 2007; 69: ; Friberg et al, BMJ 2012;344:e3522; Van Sta et al, J Thromb Haemost 2011;9:

3 Gender Differences At the time of initial presentation of atrial fibrillation, men have a higher burden of ischemic heart disease whereas women have a higher prevalence of hypertension and a history of thyroid dysfunction. The Framingham study cohort suggested that there were also higher incidences of congestive heart failure, valvular heart disease, and diabetes in women with AF. Annualized adjusted rate of thromboembolism (ischemic stroke and peripheral embolism) during off-warfarin periods among women and men with atrial fibrillation with age, prior stroke, hypertension, congestive heart failure, coronary artery disease, diabetes mellitus, and estrogen use controlled for. SPAF Analysis Although women have a lower incidence of atrial fibrillation, some studies have demonstrated a worse outcome and a higher rate of recurrence after cardioversion. SRAF Working Group, Neurology 2007; 69: ; Friberg et al, BMJ 2012;344:e3522; Van Sta et al, J Thromb Haemost 2011;9: Margaret C. Fang et al. Circulation. 2005;112: Copyright American Heart Association, Inc. All rights reserved. Gender Differences Women have a higher risk of stroke when not using anticoagulants than men hence inclusion in the CHADS2-VASc score. Antithrombotic therapy is not recommended in patients with AF (irrespective of gender) who are aged < 65 and have lone AF (i.e. truly low-risk ), as the latter have very low absolute event rates. Evidence for Aspirin is Weak ACCORDING TO THE 2012 ESC GUIDELINES: The evidence for effective stroke prevention with aspirin in AF is weak, with a potential for harm Given the availability of NOACs, the use of antiplatelet therapy (such as aspirin ) for stroke prevention in AF should be limited to the few patients who refuse any form of OAC. >60% estimated reduction in risk of stroke with NOAC vs aspirin alone 2 1. Camm AJ et al. Eur Heart J 2012; 33: Roskell et al. Thromb Haemost 2010; 104(6): We know that Warfarin Reduces the Risk of Stroke A meta-analysis of 29 trials including 28,044 participants showed: Why INR 2-3 is the target? *Dose-adjusted warfarin versus placebo. 1. Hart RG et al. Ann Intern Med 2007; 146: Connolly SJ et al. N Engl J Med 2009; 361: Connolly SJ et al. N Engl J Med 2010; 363: Fuster, V. et al. J Am Coll Cardiol 2006;48:e149-e246 INR 2.0 to % (and even <50%) of time within target INR 1.8 to 2.5 for the elderly not recommended My practice INR 2.2 to 2.8 forces tighter control 3

4 Warfarin Has Practical Limitations Warfarin limitations and fear of bleeding complications have led to global under-treatment of patients with AF requiring anticoagulants (even when the potential benefits of treatment outweigh risks). 3 In the Adelaide Stroke Incidence Study, AF accounted for 36% of all ischaemic strokes, of which 85% were inadequately anticoagulated 4 Guidelines Recommend NOACs Instead Of Warfarin 1 ACCORDING TO THE 2012 ESC GUIDELINES: this guideline now recommends [novel oral anticoagulants (NOACs)] as broadly preferable to VKA in the vast majority of patients with non-valvular AF, when used as studied in the clinical trials performed so far. Based on data from three big trials (amongst others): 1. ROCKET-AF Xarelto vs warfarin (14,264 pts) 2. ARISTOTLE Eliquis vs warfarin (18,113 pts) 3. RE-LY Pradaxa vs warfarin (18,021 pts) 1. Turpie AG. Eur Heart J 2008; 29: Khoo CW et al. Int J Clin Pract 2009; 63: Lin PJ et al. Eur Heart J Suppl 2005; 7(suppl E): E15 E Leyden JM et al. Stroke 2013; 44: Camm AJ et al. Eur Heart J 2012; 33: XARELTO (Rivaroxaban): Efficacy and Safety Vs. Warfarin 1-3 ROCKET-AF Outcome measure Stroke or systemic embolism (primary endpoint)* Ischaemic stroke Major and clinically relevant non-major bleeding Intracranial haemorrhage Xarelto 20 mg/15 mg OD (RRR vs. warfarin; n=7,131) 1,2 Non-inferior (p<0.001 for noninferiority; for superiority) 33% (p=0.02) *Analysis for non-inferiority performed using the per-protocol population. Analysis for superiority performed using the ITT population. Analysis performed using the safety on-treatment population. A pre-specified analysis of patients taking Xarelto 15 mg reported results consistent with the overall trial. 3 ARISTOTLE Outcome measure Stroke or systemic embolism (primary endpoint)* Ischaemic or uncertain type of stroke* Major bleeding Eliquis (Apixaban): Efficacy and Safety Vs. Warfarin 1 Intracranial haemorrhage *Analysis performed using the ITT population. Analysis performed using the safety on-treatment population. Eliquis 5 mg/2.5 mg BD (RRR vs. warfarin; n=9,120) 21% (p=0.01) 31% (p<0.001) 58% (p<0.001) ITT=intent-to-treat; RRR=relative risk reduction; =not statistically significant. 1. Patel MR et al. N Engl J Med 2011; 365: Patel MR et al. N Engl J Med 2011; 365: (supplementary appendix). 3. Fox KA et al. Eur Heart J 2011; 32: ITT=intent-to-treat; RRR=relative risk reduction; =not statistically significant. 1. Granger CB et al. New Engl J Med 2011; 365: PRADAXA (Dabigatran): Efficacy And Safety Vs. Warfarin 1,2 RE-LY Outcome measure (ITT population) Stroke or systemic embolism (primary endpoint) Ischaemic stroke PRADAXA 150 mg BD (RRR vs. warfarin; n=6,076) 35% (p=0.001 for superiority) 24% (p=0.003) PRADAXA 110 mg BD (RRR vs. warfarin; n=6,015) Non-inferior (p=0.001 for non-inferiority; for superiority) Major bleeding * 20% (p=0.003) Intracranial haemorrhage 59% (p<0.001) 70% (p<0.001) In patients aged <75 years, PRADAXA 150 mg BD reduced the risk of major bleeding by 30% vs. warfarin (p<0.001; post hoc analysis).* 3 Who Should Take Warfarin in the Era of NOACs? Warfarin should be used: in those NVAF patients contraindicated for NOACs, including those with severe renal impairment in patients who have valvular AF NOACs are contraindicated for patients with mechanical/prosthetic valves NVAF is defined as atrial fibrillation without the presence of haemodynamically-relevant mitral valve stenosis or prosthetic heart valve (mechanical or biological) 1 ITT=intent-to-treat; RRR=relative risk reduction; =not statistically significant. 1. Connolly SJ et al. N Engl J Med 2009; 361: Connolly SJ et al. N Engl J Med 2010; 363: Eikelboom JW et al. Circulation 2011; 123: Ezekowitz MD and Kent AP. Available from 4

5 Maintaining sinus rhythm Antiarrhythmic drugs Catheter ablation Rate vs rhythm control Conclusion of the AFFIRM Trial (from 2002): None of the presumed benefits of rhythm control noted above were confirmed in this study. The implication is that rate control should be considered a primary approach to therapy and that rhythm control, if used, may be abandoned early if it is not fully satisfactory. Our data also suggest that continuous anticoagulation is warranted in all patients with atrial fibrillation and risk factors for stroke, even when sinus rhythm appears to be restored and maintained. Rate control strategies Rate control strategy Lenient HR < 110 bpm at rest Strict HR < 80 bpm and < 110 bpm with moderate exercise Is it really that simple? Not all patients tolerate AF Not all patients tolerate high heart rates Not all patients have controlled rates with exercise Catheter ablation Role of PVI in practice Known as pulmonary vein isolation (PVI) Class 1A indication for patients with symptomatic, paroxysmal AF and who have failed or become intolerant to one or more antiarrhythmic drugs, RFA recommended In current practice, non-indicated are: Age > 75 Severely dilated left atrium Permanent AF > 2 years 5

6 Is PVI a cure for AF? Take Home Points Classic questions: Can I stop my anticoagulants? Can I stop my anti-arrhythmics? How can you make sure that I m not in the 30% group that gets AF again? Operator dependent Managing risk factors hypertension, sleep apnoea Expect it may happen longer in AF, larger atria, underlying LV dysfunction, sleep apnoea non-compliance What can I do when I get AF again? Women are at higher risk of stroke from AF than men, but when all else is considered, the absolute risk is not very high New oral anticoagulants are available with different dosing, monitoring profile and reversibility options than warfarin Specific and well established treatment algorithm for AF when rhythm control is treatment aim amiodarone is often necessary Increasing awareness of need for patients to monitor their own heart rate palpation, BP machine, smart phone Rate control is an appropriate treatment option for many patients with AF important to recognise when it s not the first line option Pulmonary vein isolation (PVI) using catheter ablation provides definitive treatment option but at cost of invasiveness and established failure rate of 20-30% at 1 year; high cost to society (patient selection critical) without significant mortality benefit 6