Secondary Stroke Prevention. Lawrence R. Wechsler, M.D.

Transcription

1 Secondary Stroke Prevention Lawrence R. Wechsler, M.D.

2 Outline Risk factor modification Antiplatelet therapy Anticoagulation Intracranial stenosis PFO and stroke

3 Risk Factor Control Hypertension - < 140/90, 130/80 DM Dyslipidemia - LDL < Diabetes - HbA1c < 7.0 Obesity Metabolic syndrome Physical inactivity Nutrition Obstructive sleep apnea Cigarette smoking cessation Eliminate heavy alcohol

4 Antiplatelet Agents Mechanism Dosing Aspirin COX inhibition Once daily Clopidogrel Ticlopidine ADP Receptor antagonist ADP Receptor antagonist Twice daily Twice daily Aggrenox ASA/Dipyridamole Twice daily Cilostazol Phosphodiesterase Inhibitor Twice daily

5 Aspirin Efficacy by Dose: Meta-Analyses in Patients With Stroke or TIA* Dose (mg/day) Low Dose Medium Dose Algra, van Gijn Johnson High Dose RRR (%) ± 95% CI * Endpoint: stroke, MI, or vascular death.

6 MATCH Study Design Recent TIA or IS (within 3 months) AND high risk of recurrent ischemic events* R Clopidogrel + Aspirin (N=3,797 patients) Clopidogrel + Placebo (N=3,802 patients) IS=ischemic stroke; R=randomization; TIA=transient ischemic attack. * Past history of IS, MI, angina pectoris, symptomatic PAD, or diabetes within 3 years prior to randomization. Between months 1 and 18, patients will be contacted by phone on a monthly basis. Diener H-C et al on behalf of the MATCH Investigators. Cerebrovasc Dis. 2004;17:

7 MATCH: Primary End Point: MI, IS, Vascular Death, or Rehospitalization for an Acute Ischemic Event Cumulative Event Rate N=7,599 Clopidogrel + Placebo Clopidogrel + ASA 6.4%* Overall Relative Risk Reduction P = Months of Follow Up ITT analysis. Diener C. 13 th European Stroke Conference. Mannheim, Germany. May 2004

8 MATCH Main Safety Outcomes Type of Bleeding Events (%) Clopidogrel + Placebo (N= 3,781) Clopidogrel + ASA (N= 3,759) % Absolute Difference (95% CI) P value Life-threatening Events (%) 49 (1.30) 96 (2.55) 1.26 (0.64, 1.88) <0.001 Fatal 11 (0.29) 16 (0.43) 0.13 (-0.14, 0.40) Nonfatal 38 (1.01) 81 (2.15) 1.15 (0.59, 1.71) Major Bleeding Events (%) 22 (0.58) 73 (1.94) 1.36 (0.86,1.86) <0.001 *Leading to modification of the drug regimen ASA=aspirin; CI=confidence interval. Diener C. 13 th European Stroke Conference. Mannheim, Germany. May 2004

9 MATCH: Conclusions Monotherapy with clopidogrel As effective as combination therapy with clopidogrel and aspirin for high risk patients with cerebrovascular disease Is safer than combination therapy with clopidogrel and aspirin Diener H-C et al. Lancet. 2004;291:

10 CHANCE Trial Randomized double blind trial of clopidogrel + asa v. asa alone within 24 hours of minor stroke or high risk TIA pts in 114 centers in China 3.5% absolute reduction in stroke events over 90 days No increase in hemorrhages. Wang et al. NEJM 2013

11 WARFARIN VS. ASPIRIN FOR RECURRENT STROKE STUDY (WARSS) 2206 patients over 2 years Randomized, double blinded study Non-cardioembolic stroke, non-operable atherosclerotic disease within 30 days of event Warfarin INR v. ASA 325 mg Primary endpoint recurrent ischemic stroke or death Secondary endpoints TIA, MI 0 Probability of Event (%) Warfarin Days after Randomization Aspirin Mohr J, et al, NEJM 2001

12 Warfarin-Aspirin for Symptomatic Intracranial Disease Study (WASID) TIA or minor stroke within 90 days 50-99% stenosis of a major intracranial artery (carotid, MCA, VA, basilar artery) documented by catheter angiography ASA 1300 mg / day v. Warfarin INR 2-3 Study stopped by DSMB after 569 of 806 patients enrolled Mean follow-up 1.8 yrs Aspirin Warfarin Years after Enrollment Chimowitz et al. NEJM 2011

13 SAMMPRIS Randomized trial of intensive medical therapy v. intensive med therapy + wingspan stent TIA or Minor stroke with 70-99% intracranial stenosis Enrollment stopped after 451 pts 30 day stroke and death 14.7% stent v. 5.8% IMT IMT includes ASA, Clopidogrel 90 days, aggressive risk factor reduction and lifestyle modification Chimowitz et al. NEJM 2011

14 Atrial Fibrillation and Stroke: Summary of Randomized Studies % Stroke/Year % 72% 5.5% 5.5% AFASAK 67% 2.3% 7.4% 42% 3.6% 6.3% 86% 0.4% Warfarin Aspirin Placebo % decrease in events 26% 3.0% 2.9% 4.5% 79% 0.9% 4.3% SPAF1 SPAF2 BAATAF CAFS SPINAF Morley J, et al. Am J Card. 1996;77:38A-44A.

15 New Anticoagulants Mechanism Dabigatran Rivaroxaban Apixaban Edoxaban Direct thrombin inh Factor Xa inhibitor Factor Xa inhibitor Factor Xa inhibitor Frequency Twice daily Once daily Twice daily Once daily Onset 2-3 hrs 3 hrs 3 hrs 1-3 hrs Half life hrs 7-11 hrs 9-14 hrs hrs Clearance Renal Renal GI/Renal GI/Renal

16 New Anticoagulants Advantages No monitoring Rapid onset of action Once or twice daily Lower stroke risk Reduced overall bleeding risk Reduced ICH Fewer interactions Disadvantages No reversal agent Increased GI bleeds Compliance important Expense Renal adjustment

17 Cardiac Monitoring CRYSTAL AF EMBRACE Sanna et al. NEJM 2014 Gladstone et al. NEJM 2014

18 What We Know About PFOs Present in ~ 10-12% of population Found in up to 26% on autopsy Greater frequency in patients with stroke Even greater frequency (45-55%) in young patients with cryptogenic stroke Causative or innocent bystander? Does endovascular closure prevent recurrent stroke?

19 PFO Device RCTs CLOSURE RESPECT PC TRIAL Pts Design Superiority Endpoint Superiority Inclusion Stroke and TIA Stroke Stroke, TIA*, Emb Endpoint Stroke, TIA, Dth Stroke, Dth Str, TIA, Dth, Emb Followup 2 yrs 25 endpoints 4 yrs Duration 5 yrs 8 yrs 10 yrs Device event rate 3.1% (1.5% yr) 2.2% (0.44%/yr) 3.4% (0.85%/yr) Medical event rate 3.4% (1.7% yr) 6.5% (1.3%/yr) 5.2% (1.3%/yr) * Documented MRI lesion

20 THANK YOU!