研究经皮闭合左心耳和华法林对房颤预防脑卒中影响的课件

PROTECT AFPROTECT AF研究：经皮闭合左心耳和华法林对房颤研究：经皮闭合左心耳和华法林对房颤 预防脑卒中影响的前瞻性随机研究预防脑卒中影响的前瞻性随机研究 PROTECT AFPROTECT AF trialstrials： Randomized Prospective Trial of Randomized Prospective Trial of PercutaneousPercutaneous LAA LAA Closure Closure vsvs WarfarinWarfarin for Stroke Prevention in AF for Stroke Prevention in AF David Holmes, David Holmes, MD;VivekMD;Vivek Reddy, MD; Reddy, MD; ZoltanZoltan TuriTuri, MD, MD，et alet al Relevant Financial Relevant Financial Relationship(sRelationship(s) ) Mayo receives research support from Mayo receives research support from AtritechAtritech and may receive royaltiesand may receive royalties PROTECT AF TrialPROTECT AF Trial Sponsor:Sponsor: AtritechAtritech (Plymouth, MN) (Plymouth, MN) Principal Investigator:Principal Investigator: David HolmesDavid Holmes Clinical Trials Clinical Trials IndentifierIndentifier: : NCT00129545NCT00129545 Prospective, Multicenter Randomized Trial Prospective, Multicenter Randomized Trial of of PercutaneousPercutaneous Left Left AtrialAtrial Appendage Occlusion Appendage Occlusion vsvs Long-term Long-term WarfarinWarfarin Therapy in Patients with Non- Therapy in Patients with Non- ValvularValvular AtrialAtrial Fibrillation Fibrillation Facts about Facts about AtrialAtrial Fibrillation (AF) Fibrillation (AF) AF is the most common cardiac arrhythmiaAF is the most common cardiac arrhythmia Affects more than 3 million individuals in the USAffects more than 3 million individuals in the US Projected to increase to 16 million by 2050Projected to increase to 16 million by 2050 Patients with AF have a 5-fold higher risk of strokePatients with AF have a 5-fold higher risk of stroke Over 87% of strokes are Over 87% of strokes are thromboembolicthromboembolic Greater than 90% of thrombus accumulation Greater than 90% of thrombus accumulation originates in the Left originates in the Left AtrialAtrial Appendage (LAA) Appendage (LAA) Stroke is the number one cause of long-term Stroke is the number one cause of long-term disability and the third leading cause of death in disability and the third leading cause of death in patients with AFpatients with AF Non-Non-ValvularValvular AtrialAtrial Fibrillation Stroke Prevention Fibrillation Stroke Prevention Medical RxMedical Rx 3000838-10 Cooper: Arch Cooper: Arch IntInt Med 166, 2006 Med 166, 2006 Lip: Lip: ThrombThromb Res 118, 2006 Res 118, 2006 WarfarinWarfarin cornerstone of therapy cornerstone of therapy Assuming 51 ischemic strokes/1000 pt-yrAssuming 51 ischemic strokes/1000 pt-yr Adjusted standard dose Adjusted standard dose warfarinwarfarin prevented prevented 28 strokes at expense of 11 fatal bleeds28 strokes at expense of 11 fatal bleeds Aspirin prevented 16 strokes at expense Aspirin prevented 16 strokes at expense of 6 fatal bleedsof 6 fatal bleeds WarfarinWarfarin 60-70% risk reduction 60-70% risk reduction vsvs no treatment no treatment 30-40% risk reduction 30-40% risk reduction vsvs aspirin aspirin Challenges in Treating AFChallenges in Treating AF However However warfarinwarfarin is not always well-tolerated is not always well-tolerated Narrow therapeutic range (INR between 2.0 3.0) Narrow therapeutic range (INR between 2.0 3.0) Effectiveness is impacted by interactions with Effectiveness is impacted by interactions with some foods and medications some foods and medications Requires frequent monitoring and dose adjustments Requires frequent monitoring and dose adjustments Published reports indicate that less than 50% of patients Published reports indicate that less than 50% of patients eligible are being treated with eligible are being treated with warfarinwarfarin due to tolerance due to tolerance or non-compliance issuesor non-compliance issues SPORTIF trials suggest only 60% of patients treated are SPORTIF trials suggest only 60% of patients treated are within a therapeutic INR range, while 29% have INR within a therapeutic INR range, while 29% have INR levels below 2.0 and 15% have levels above 3.0levels below 2.0 and 15% have levels above 3.0 Watchman LAA Closure TechnologyWatchman LAA Closure Technology The The WATCHMAN WATCHMAN LAA LAA Closure Closure Technology Technology is is designed designed to to prevent prevent embolizationembolization of of thrombi thrombi that that may form in the LAAmay form in the LAA The The WATCHMANWATCHMAN Left Left AtrialAtrial Appendage Appendage Closure Closure Technology Technology is is intended intended as as an an alternative alternative to to warfarinwarfarin therapy therapy for for patients patients with with non-non-valvularvalvular atrialatrial fibrillation fibrillation WATCHMAN LAA Closure Device in situWATCHMAN LAA Closure Device in situ 3000838-18 PROTECT AF Clinical Trial DesignPROTECT AF Clinical Trial Design Prospective, Prospective, randomized randomized study study of of WATCHMAN WATCHMAN LAA LAA Device Device vs. vs. Long-term Long-term WarfarinWarfarin Therapy Therapy 2:1 allocation ratio device to control2:1 allocation ratio device to control 800 Patients enrolled from Feb 2005 to Jun 2008800 Patients enrolled from Feb 2005 to Jun 2008 Device Group (463)Device Group (463) Control Group (244)Control Group (244) Roll-in Group (93)Roll-in Group (93) 59 Enrolling Centers (U.S. points; 600 600 patient-yr, patient-yr, then every 150 pt-yr thereafterthen every 150 pt-yr thereafter Successful Successful non-inferiority non-inferiority based based on on first first time time success criterion metsuccess criterion met Success criterion defined on probability scaleSuccess criterion defined on probability scale 97.5% 97.5% probability probability that that primary primary efficacy efficacy event event rate rate for WATCHMAN is less than two times controlfor WATCHMAN is less than two times control 5% 5% probability probability that that primary primary efficacy efficacy event event rate rate for for WATCHMAN is less than controlWATCHMAN is less than control PROTECT AF Statistical OverviewPROTECT AF Statistical Overview 3000838-45 Key Participation CriteriaKey Participation Criteria Key Inclusion CriteriaKey Inclusion Criteria Age 18 years or olderAge 18 years or older Documented non-Documented non-valvularvalvular AF AF Eligible for long-term Eligible for long-term warfarinwarfarin therapy, and no other therapy, and no other conditions that would require long-term conditions that would require long-term warfarinwarfarin therapy therapy Calculated CHADS2 score Calculated CHADS2 score 1 1 Key Exclusion CriteriaKey Exclusion Criteria NYHA Class IV Congestive Heart FailureNYHA Class IV Congestive Heart Failure ASD and/or ASD and/or atrialatrial septalseptal repair or closure device repair or closure device Planned ablation procedure within 30 days of potential Planned ablation procedure within 30 days of potential WATCHMAN Device implantWATCHMAN Device implant Symptomatic carotid diseaseSymptomatic carotid disease LVEF 0.9990.9990.9980.998 pt-yrpt-yr(0.0, 0.6)(0.0, 0.6)(0.7, 3.7)(0.7, 3.7)(0.00, 0.45)(0.00, 0.45) DeviceDeviceControlControlPosterior probabilitiesPosterior probabilities Randomization allocation (2 device:1 Randomization allocation (2 device:1 control)control) Risk/Benefit AnalysisRisk/Benefit Analysis Intent-to-treat analysisIntent-to-treat analysis Primary endpoint (intent to treat) achievedPrimary endpoint (intent to treat) achieved Other statistically significant endpoint findingsOther statistically significant endpoint findings NoninferiorityNoninferiority for for the the primary primary efficacy efficacy event event rate rate 32% 32% lower lower in device groupin device group NoninferiorityNoninferiority for all strokes 26% lower in device group for all strokes 26% lower in device group Superiority Superiority for for hemorrhagic hemorrhagic stroke stroke 91% 91% lower lower in in device device groupgroup NoninferiorityNoninferiority for for mortality mortality rate rate 39% 39% lower lower rate rate in in device device groupgroup Increased Increased rate rate of of primary primary safety safety events events for for the the device device group group relative to the control group relative to the control group Most Most events events in in the the device device group group were were procedural procedural effusions effusions that decreased over the course of the studythat decreased over the course of the study 87% of patients were able to discontinue 87% of patients were able to discontinue warfarinwarfarin at 45 days at 45 days 3000838-120 SummarySummary Long-term Long-term warfarinwarfarin treatment treatment of of patients patients with with AF AF has has been been found effective, but presents difficulties and riskfound effective, but presents difficulties and risk PROTECT PROTECT AF AF trial trial was was a a randomized, randomized, controlled, controlled, statistically statistically valid valid study study to to evaluate evaluate the the WATCHMAN WATCHMAN device device compared compared to to warfarinwarfarin In In PROTECT PROTECT AF, AF, hemorrhagic hemorrhagic stroke stroke risk risk is is significantly significantly lower with the d