Risk Stratification for Stroke Prevention in Patients with Atrial Fibrillation: The emerging role of biomarkers

Transcription

1 Risk Stratification for Stroke Prevention in Patients with Atrial Fibrillation: The emerging role of biomarkers Banff 2013 CP

2 Meta-Analysis of Stroke 5 Randomized Trials Placebo Stroke Rate 4.5%/yr Risk factors R Risk Previous stroke/tia 2.5 History of hypertension 1.6 Advanced age (continuous) 1.4/10 yr Diabetes mellitus 1.7 History of CHF 1.4 Collaborative Analysis AFib Investigators Arch Intern Med, 1994 Age related Pt aged 60 yr + No risk factors Stroke rate 1%/yr Kopecky: NEJM, 1987 CP

3 Atrial Fibrillation and Thromboembolism Is it atrial fibrillation or the company it keeps? CP

4 Survival free of stroke/tia (%) Survival from death (%) Natural History of Lone AFib (Stroke/TIA) 71 patients Median age yr Paroxysmal AFib No SHD/no HTN Mean F-U 30 yr Cumulative Survival P=0.120 Observed Expected Years after diagnosis of AFib Cumulative Survival Free of Stroke/TIA Expected Observed Jahangir, Circ P= Years after diagnosis of AFib CP

5 Survival free of stroke/tia (%) Survival from death (%) 71 patients Median age yr Paroxysmal AFib No SHD/no 90HTN Mean F-U 30 yr Age Natural History of Lone AFib (Stroke/TIA) Jahangir et al 100 Multivariate analysis Predictors of stroke/tia 80 Development of hypertension Expected Observed P= Cumulative Survival P=0.120 Observed Expected Years after diagnosis of AFib Cumulative Survival Free of Stroke/TIA P=0.014 Expected Observed Years after diagnosis of AFib CP

6 Performance of Contemporary Risk Stratification Schemes Study AFI, 94 SPAF, 95 CHADS 2 CHADS 2 revised Framingham NICE, 2006 ACC/AHA/ESC, 2006 ACCP, 2008 Birmingham, 2009 Low Intermediate High Range C statistic Lip: Chest,

7 CHADS 2 Score and Left Atrial Thrombi in AF Case control study 110 pt NVAF Cases % Distribution of Scores Controls (mean 1.6) Cases (mean 2.8) Considerable overlap LAA thrombus TEE Wysosinski: AHJ, 2010 Scores

8 Recurrence free rate Recurrence free rate Recurrence free rate Relationship Between CHADS 2 Score and Recurrence After RFA for Paroxysmal AF 238 pts Paroxysmal AF Median FU 5 yrs Recurrence after a single procedure 50.8% CHADS 2 score=1-2 2 Years CHADS 2 score=0 Long-Term Recurrence After A Single Procedure (Stratified by Blanking Period) P<0.001 CHADS 2 score Months 1 Year CHADS 2 score=0 CHADS 2 score=1-2 CHADS 2 score= CHADS 2 score= CHADS 2 score 3 P< Months CHADS P< score Months Chao: H Rhythm,

9 Stroke rate/100 pt-yrs Risk of Stroke and CHADS 2 Score Aspirin arm in ACTIVE-W National Registry of AFib CHADS 2 Score Healey: Stroke 2008; Gage: JAMA

10 Cumulative hazard Data from AVERROES and ACTIVE Trials Hazard Ratios for Ischemia or Unspecified Stroke and Non-CNS Systemic Embolus/Patients Treated with ASA or ASA + Clopidogrel No. at risk All 4,670 CHA 2 -DS 2 -VASc score ,446 CHA 2 DS 2 -VASc score Years 2.1%/yr CHADS 2 score1 CHA 2 DS 2 -VASc score 1 Coppens et al: EHJ,

11 Just when I knew all of life s answers, they changed all the questions. CP

12 Yearly events (%) Cardiac Biomarkers and Risk of Stroke and Death RE-LY Trial Substudy (6189 Patients) Stroke/Systemic Embolism/PE/MI/Vascular Death <0.010 Troponin I ( g/l) Hijazi: Circ,

13 Implications of Involvement of a Biomarker in the Etiology of Disease Marker of disease severity Related to comorbidites Marker of disease causation Related to risk of events 2013 MFMER

14 Atrial Fibrillation and the Risk of Stroke Potential Role of Biomarkers Risk marker? Atrial Fibrillation Risk factor Hypertension egfr Cystatin CRP IL-6 Inflammation? compliance Aortic plaque Cerebrovascular disease BNP IL-6 CRP D-dimer Dilatation/fibrosis AFib Stasis LA & LAA flow velocity Stroke risk LVH Troponins Diastolic BNP dysfunction D-dimer Prothrombotic state Stretch induced Inflammation?

15 Cumulative hazard rate Stroke and Vascular Death According to NTproBNP Levels at Randomization in RE-LY Stroke or Systemic Embolism >1402 ng/l ng/l ng/l <387 ng/l Vascular Death Months Months Hijazi Z et al: Circulation 125:1605,

16 Cumulative rate of new AFib diagnosis (%) Brain Natriuretic Peptide: A Relevant Marker to Rule Out Delayed Atrial Fibrillation in Stroke Patient Laurent Suissa, MD; Saskia Bresch, MD; Sylvain Lachaud, MD and Marie Hélène Mahagne, MD, PhD J Stroke and CV Diseases, stroke patients No history of AFib No AFib on baseline ECG In-hospital Holter monitoring (6.8 days median) AFib detection 17.3% Temporal Dynamics of AFib Detection Time of AFib detection (day) Our data indicate that a BNP level 131 pg/ml might rule out delayed AFib in stroke survivors and could be included in algorithms for AFib detection

17 LAA thrombus -43% of recent thromboembolism pt Manning: Arch Int med, 1995 CP

18 Biomarkers in AFib Future Prospects Prediction of treatment responses Drugs Ablation Assessment of bleeding risk with new oral anticoagulants Genetic markers for tailoring of warfarin dosage Evolution of proteomics and understanding of biological systems of disease New biomarkers Understanding pathophysiology of AF New drug targets Allow early disease detection 2013 MFMER

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