Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation a randomized clinical trial

PROTECT AF Steering Committee and Investigators

Research output: Contribution to journalArticle

352 Citations (Scopus)

Abstract

Importance While effective in preventing stroke in patients with atrial fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions. OBJECTIVE To determine whether a local strategy of mechanical left atrial appendage (LAA) closure was noninferior to warfarin. Design, Setting, and Participants Protect AFwas a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor (CHADS2score≥1). Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October 2012. Noninferiority required a posterior probability greater than 97.5%and superiority a probability of 95%or greater; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups. Interventions Left atrial appendage closure with the device (n = 463) or warfarin (n = 244; target international normalized ratio, 2-3). Main Outcomes and Measures A composite efficacy end point including stroke, systemic embolism, and cardiovascular/unexplained death, analyzed by intention-to-treat. Results At a mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events among 463 patients (8.4%) in the device group for a primary event rate of 2.3 events per 100 patient-years, compared with 34 events among 244 patients (13.9%) for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate ratio, 0.60; 95%credible interval, 0.41-1.05), meeting prespecified criteria for both noninferiority (posterior probability, <99.9%) and superiority (posterior probability, 96.0%). Patients in the device group demonstrated lower rates of both cardiovascular mortality (1.0 events per 100 patient-years for the device group [17/463 patients, 3.7%] vs 2.4 events per 100 patient-years with warfarin [22/244 patients, 9.0%]; hazard ratio [HR], 0.40; 95%CI, 0.21-0.75; P =.005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients, 12.3%] vs 4.8 events per 100 patient-years with warfarin [44/244 patients, 18.0%]; HR, 0.66; 95%CI, 0.45-0.98; P =.04). Conclusions and Relevance After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.

Original languageEnglish (US)
Pages (from-to)1988-1998
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume312
Issue number19
DOIs
StatePublished - Nov 19 2014
Externally publishedYes

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Atrial Appendage
Warfarin
Atrial Fibrillation
Randomized Controlled Trials
Stroke
Equipment and Supplies
Embolism
Mortality
International Normalized Ratio

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation a randomized clinical trial. / PROTECT AF Steering Committee and Investigators.

In: JAMA - Journal of the American Medical Association, Vol. 312, No. 19, 19.11.2014, p. 1988-1998.

Research output: Contribution to journalArticle

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title = "Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation a randomized clinical trial",
abstract = "Importance While effective in preventing stroke in patients with atrial fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions. OBJECTIVE To determine whether a local strategy of mechanical left atrial appendage (LAA) closure was noninferior to warfarin. Design, Setting, and Participants Protect AFwas a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor (CHADS2score≥1). Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October 2012. Noninferiority required a posterior probability greater than 97.5{\%}and superiority a probability of 95{\%}or greater; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups. Interventions Left atrial appendage closure with the device (n = 463) or warfarin (n = 244; target international normalized ratio, 2-3). Main Outcomes and Measures A composite efficacy end point including stroke, systemic embolism, and cardiovascular/unexplained death, analyzed by intention-to-treat. Results At a mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events among 463 patients (8.4{\%}) in the device group for a primary event rate of 2.3 events per 100 patient-years, compared with 34 events among 244 patients (13.9{\%}) for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate ratio, 0.60; 95{\%}credible interval, 0.41-1.05), meeting prespecified criteria for both noninferiority (posterior probability, <99.9{\%}) and superiority (posterior probability, 96.0{\%}). Patients in the device group demonstrated lower rates of both cardiovascular mortality (1.0 events per 100 patient-years for the device group [17/463 patients, 3.7{\%}] vs 2.4 events per 100 patient-years with warfarin [22/244 patients, 9.0{\%}]; hazard ratio [HR], 0.40; 95{\%}CI, 0.21-0.75; P =.005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients, 12.3{\%}] vs 4.8 events per 100 patient-years with warfarin [44/244 patients, 18.0{\%}]; HR, 0.66; 95{\%}CI, 0.45-0.98; P =.04). Conclusions and Relevance After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.",
author = "{PROTECT AF Steering Committee and Investigators} and Reddy, {Vivek Y.} and Horst Sievert and Jonathan Halperin and Doshi, {Shephal K.} and Maurice Buchbinder and Petr Neuzil and Kenneth Huber and Brian Whisenant and Saibal Kar and Vijay Swarup and Nicole Gordon and David Holmes and Holmes, {David R.} and Larry Chinitz and Pam Douglas and John Gurley and Peter Sick and Turi, {Zoltan G.} and Hustead, {Stephen T.} and Asinger, {Richard W.} and Wendy Shear and Brian Lew and Anthony Plucinski and Eve Rogers and Sven Mobius-Winkler and Kelly Tucker and Shephal Doshi and Marwan Bahu and Ramon Quesada and Vivek Reddy and Steven Almany and Ashok Garg and Gregory Mishkel and Stephen Ramee and Brijeshwar Maini and Steven Burstein and Rodney Horton and Paul Mahoney and Stuart Adler and Kimberly Skelding and Miland Shah and Steven Yakubov and Angel Leon and Block, {Peter C.} and Peter Fail and Mark Reisman and Gery Tomassoni and Vishwajeth Bhoopalam and William Anderson and Robert Pickett",
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TY - JOUR

T1 - Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation a randomized clinical trial

AU - PROTECT AF Steering Committee and Investigators

AU - Reddy, Vivek Y.

AU - Sievert, Horst

AU - Halperin, Jonathan

AU - Doshi, Shephal K.

AU - Buchbinder, Maurice

AU - Neuzil, Petr

AU - Huber, Kenneth

AU - Whisenant, Brian

AU - Kar, Saibal

AU - Swarup, Vijay

AU - Gordon, Nicole

AU - Holmes, David

AU - Holmes, David R.

AU - Chinitz, Larry

AU - Douglas, Pam

AU - Gurley, John

AU - Sick, Peter

AU - Turi, Zoltan G.

AU - Hustead, Stephen T.

AU - Asinger, Richard W.

AU - Shear, Wendy

AU - Lew, Brian

AU - Plucinski, Anthony

AU - Rogers, Eve

AU - Mobius-Winkler, Sven

AU - Tucker, Kelly

AU - Doshi, Shephal

AU - Bahu, Marwan

AU - Quesada, Ramon

AU - Reddy, Vivek

AU - Almany, Steven

AU - Garg, Ashok

AU - Mishkel, Gregory

AU - Ramee, Stephen

AU - Maini, Brijeshwar

AU - Burstein, Steven

AU - Horton, Rodney

AU - Mahoney, Paul

AU - Adler, Stuart

AU - Skelding, Kimberly

AU - Shah, Miland

AU - Yakubov, Steven

AU - Leon, Angel

AU - Block, Peter C.

AU - Fail, Peter

AU - Reisman, Mark

AU - Tomassoni, Gery

AU - Bhoopalam, Vishwajeth

AU - Anderson, William

AU - Pickett, Robert

PY - 2014/11/19

Y1 - 2014/11/19

N2 - Importance While effective in preventing stroke in patients with atrial fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions. OBJECTIVE To determine whether a local strategy of mechanical left atrial appendage (LAA) closure was noninferior to warfarin. Design, Setting, and Participants Protect AFwas a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor (CHADS2score≥1). Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October 2012. Noninferiority required a posterior probability greater than 97.5%and superiority a probability of 95%or greater; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups. Interventions Left atrial appendage closure with the device (n = 463) or warfarin (n = 244; target international normalized ratio, 2-3). Main Outcomes and Measures A composite efficacy end point including stroke, systemic embolism, and cardiovascular/unexplained death, analyzed by intention-to-treat. Results At a mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events among 463 patients (8.4%) in the device group for a primary event rate of 2.3 events per 100 patient-years, compared with 34 events among 244 patients (13.9%) for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate ratio, 0.60; 95%credible interval, 0.41-1.05), meeting prespecified criteria for both noninferiority (posterior probability, <99.9%) and superiority (posterior probability, 96.0%). Patients in the device group demonstrated lower rates of both cardiovascular mortality (1.0 events per 100 patient-years for the device group [17/463 patients, 3.7%] vs 2.4 events per 100 patient-years with warfarin [22/244 patients, 9.0%]; hazard ratio [HR], 0.40; 95%CI, 0.21-0.75; P =.005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients, 12.3%] vs 4.8 events per 100 patient-years with warfarin [44/244 patients, 18.0%]; HR, 0.66; 95%CI, 0.45-0.98; P =.04). Conclusions and Relevance After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.

AB - Importance While effective in preventing stroke in patients with atrial fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions. OBJECTIVE To determine whether a local strategy of mechanical left atrial appendage (LAA) closure was noninferior to warfarin. Design, Setting, and Participants Protect AFwas a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor (CHADS2score≥1). Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October 2012. Noninferiority required a posterior probability greater than 97.5%and superiority a probability of 95%or greater; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups. Interventions Left atrial appendage closure with the device (n = 463) or warfarin (n = 244; target international normalized ratio, 2-3). Main Outcomes and Measures A composite efficacy end point including stroke, systemic embolism, and cardiovascular/unexplained death, analyzed by intention-to-treat. Results At a mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events among 463 patients (8.4%) in the device group for a primary event rate of 2.3 events per 100 patient-years, compared with 34 events among 244 patients (13.9%) for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate ratio, 0.60; 95%credible interval, 0.41-1.05), meeting prespecified criteria for both noninferiority (posterior probability, <99.9%) and superiority (posterior probability, 96.0%). Patients in the device group demonstrated lower rates of both cardiovascular mortality (1.0 events per 100 patient-years for the device group [17/463 patients, 3.7%] vs 2.4 events per 100 patient-years with warfarin [22/244 patients, 9.0%]; hazard ratio [HR], 0.40; 95%CI, 0.21-0.75; P =.005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients, 12.3%] vs 4.8 events per 100 patient-years with warfarin [44/244 patients, 18.0%]; HR, 0.66; 95%CI, 0.45-0.98; P =.04). Conclusions and Relevance After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.

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