Background Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. Methods In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran — 110 mg or 150 mg twice daily — or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. Results Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P = 0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P = 0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P = 0.13) and 3.64% per year with 150 mg of dabigatran (P = 0.051). Conclusions In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.)

/pdf/dabigatran-versus-warfarin-in-patients-with-atrial-it337cdbto.pdf

Dabigatran versus warfarin in patients with atrial fibrillation

WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Blaha, MD, MPH Stephanie E. Chiuve, ScD Mary Cushman, MD, MSc, FAHA Sandeep R. Das, MD, MPH, FAHA Rajat Deo, MD, MTR Sarah D. de Ferranti, MD, MPH James Floyd, MD, MS Myriam Fornage, PhD, FAHA Cathleen Gillespie, MS Carmen R. Isasi, MD, PhD, FAHA Monik C. Jiménez, ScD, SM Lori Chaffin Jordan, MD, PhD Suzanne E. Judd, PhD Daniel Lackland, DrPH, FAHA Judith H. Lichtman, PhD, MPH, FAHA Lynda Lisabeth, PhD, MPH, FAHA Simin Liu, MD, ScD, FAHA Chris T. Longenecker, MD Rachel H. Mackey, PhD, MPH, FAHA Kunihiro Matsushita, MD, PhD, FAHA Dariush Mozaffarian, MD, DrPH, FAHA Michael E. Mussolino, PhD, FAHA Khurram Nasir, MD, MPH, FAHA Robert W. Neumar, MD, PhD, FAHA Latha Palaniappan, MD, MS, FAHA Dilip K. Pandey, MBBS, MS, PhD, FAHA Ravi R. Thiagarajan, MD, MPH Mathew J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Rodriguez, MD, MPH, FAHA Gregory A. Roth, MD, MPH Wayne D. Rosamond, PhD, FAHA Comilla Sasson, MD, PhD, FAHA Amytis Towfighi, MD Connie W. Tsao, MD, MPH Melanie B. Turner, MPH Salim S. Virani, MD, PhD, FAHA Jenifer H. Voeks, PhD Joshua Z. Willey, MD, MS John T. Wilkins, MD Jason HY. Wu, MSc, PhD, FAHA Heather M. Alger, PhD Sally S. Wong, PhD, RD, CDN, FAHA Paul Muntner, PhD, MHSc On behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2017 Update

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Nancy M. Albert, PhD, RN, FAHA

Biykem Bozkurt, MD, PhD, FACC, FAHA

Ralph G. Brindis, MD, MPH, MACC

Mark A. Creager, MD, FACC, FAHA[#][1]

Lesley H. Curtis, PhD, FAHA

David DeMets, PhD[#][1]

Robert A

/pdf/2014-aha-acc-hrs-guideline-for-the-management-of-patients-1v8ficsqox.pdf

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

Author(s): Writing Group Members; Mozaffarian, Dariush; Benjamin, Emelia J; Go, Alan S; Arnett, Donna K; Blaha, Michael J; Cushman, Mary; Das, Sandeep R; de Ferranti, Sarah; Despres, Jean-Pierre; Fullerton, Heather J; Howard, Virginia J; Huffman, Mark D; Isasi, Carmen R; Jimenez, Monik C; Judd, Suzanne E; Kissela, Brett M; Lichtman, Judith H; Lisabeth, Lynda D; Liu, Simin; Mackey, Rachel H; Magid, David J; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Muntner, Paul; Mussolino, Michael E; Nasir, Khurram; Neumar, Robert W; Nichol, Graham; Palaniappan, Latha; Pandey, Dilip K; Reeves, Mathew J; Rodriguez, Carlos J; Rosamond, Wayne; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Woo, Daniel; Yeh, Robert W; Turner, Melanie B; American Heart Association Statistics Committee; Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2016 Update: A Report From the American Heart Association

March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

ContextAlthough amiodarone is approved by the US Food and Drug Administration only for refractory ventricular arrhythmias, it is one of the most frequently prescribed antiarrhythmic medications in the United States.ObjectiveTo evaluate and synthesize evidence regarding optimal use of amiodarone for various arrhythmias.Evidence AcquisitionSystematic search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. The search was limited to human-participant, English-language reports published between 1970 and 2007. Amiodarone was searched using the terms adverse effects, atrial fibrillation, atrial flutter, congestive heart failure, electrical storm, hypertrophic cardiomyopathy, implantable cardioverter-defibrillator, surgery, ventricular arrhythmia, ventricular fibrillation, and Wolff-Parkinson-White. Bibliographies of identified articles and guidelines from official societies were reviewed for additional references. Ninety-two identified studies met inclusion criteria and were included in the review.Evidence SynthesisAmiodarone may have clinical value in patients with left ventricular dysfunction and heart failure as first-line treatment for atrial fibrillation, though other agents are available. Amiodarone is useful in acute management of sustained ventricular tachyarrythmias, regardless of hemodynamic stability. The only role for prophylactic amiodarone is in the perioperative period of cardiac surgery. Amiodarone may be effective as an adjunct to implantable cardioverter-defibrillator therapy to reduce number of shocks. However, amiodarone has a number of serious adverse effects, including corneal microdeposits (>90%), optic neuropathy/neuritis (≤1%-2%), blue-gray skin discoloration (4%-9%), photosensitivity (25%-75%), hypothyroidism (6%), hyperthyroidism (0.9%-2%), pulmonary toxicity (1%-17%), peripheral neuropathy (0.3% annually), and hepatotoxicity (elevated enzyme levels, 15%-30%; hepatitis and cirrhosis, <3% [0.6% annually]).ConclusionAmiodarone should be used with close follow-up in patients who are likely to derive the most benefit, namely those with atrial fibrillation and left ventricular dysfunction, those with acute sustained ventricular arrhythmias, those about to undergo cardiac surgery, and those with implantable cardioverter-defibrillators and symptomatic shocks.

https://jamanetwork.com/journals/jama/articlepdf/208819/jcr70010_1312_1322.pdf

Prescribing Amiodarone: An Evidence-Based Review of Clinical Indications

Role of prophylactic anticoagulation for direct current cardioversion in patients with atrial fibrillation or atrial flutter

Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes

Background. Thegoal ofthereport wastostudy thelong-term incidence andtheindependent predictors forchronic atrial fibrillation andstroke in507pacedpatients withsick sinus syndrome, adjusting for differences inbaseline clinical variables withmultivariate analysis. Methods andResults. From1980to1989, we implanted 376dual-chamber, 19atrial, and112ventricular pacemakers totreat patients withsick sinus syndrome. After amaximumfollow-up of134months (mean: 59±38monthsforchronic atrial fibrillation, 65±37months forstroke), actuarial incidence ofchronic atrial fibrillation was 7%at1year,16%at5years,and28%at10years.Independent predictors forthis event, fromCox'sproportional hazards model, werehistory ofparoxysmal atrial fibrillation (P<.001; hazard ratio [HRJ=16.84), useofantiarrhythmic drugs before pacemaker implant (P<.001; HR=2.25), ventricular pacing mode(P=.003; HR=1.98), age (P=.005; HR=1.03), andvalvular heartdisease (P=.008; HR=2.05). Forpatients withpreimplant history ofparoxysmal atrial fibrillation, independent predictors wereprolonged episodes ofparoxysmal atrial fibrillation (P<.001; HR=2.56), longhistory of paroxysmal atrial fibrillation (P=.004; HR=2.05), ventricular pacing mode(P=.025; HR=1.69), useof antiarrhythmic drugsbefore pacemaker implant (P=.024; HR=1.71), andage (P=.04; HR=1.02). Actuarial incidence ofstroke was3%at1year,5%at5years,and13%at10years.Independent predictors forstroke werehistory ofcerebrovascular disease (P<.001; HR=5.22), ventricular pacing mode(P=.008; HR=2.61), andhistory ofparoxysmal atrial fibrillation (P=.037; HR=2.81). Conclusions. Development ofchronic atrial fibrillation andstroke inpacedpatients withsicksinus syndrome are strongly determined byclinical variables andsecondarily bythepacing modality. Ventricular pacing modepredicts chronic atrial fibrillation inpatients withpreimplant paroxysmal atrial fibrillation butnotinthose without it.(Circulation. 1993;88:1045-1053.)

Chronic Atrial Fibrillation andStroke inPaced Patients WithSickSinusSyndrome Relevance ofClinical Characteristics andPacing Modalities

BACKGROUND The goal of the report was to study the long-term incidence and the independent predictors for chronic atrial fibrillation and stroke in 507 paced patients with sick sinus syndrome, adjusting for differences in baseline clinical variables with multivariate analysis. METHODS AND RESULTS From 1980 to 1989, we implanted 376 dual-chamber, 19 atrial, and 112 ventricular pacemakers to treat patients with sick sinus syndrome. After a maximum follow-up of 134 months (mean: 59 +/- 38 months for chronic atrial fibrillation, 65 +/- 37 months for stroke), actuarial incidence of chronic atrial fibrillation was 7% at 1 year, 16% at 5 years, and 28% at 10 years. Independent predictors for this event, from Cox9s proportional hazards model, were history of paroxysmal atrial fibrillation (P CONCLUSIONS Development of chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome are strongly determined by clinical variables and secondarily by the pacing modality. Ventricular pacing mode predicts chronic atrial fibrillation in patients with preimplant paroxysmal atrial fibrillation but not in those without it.

Richard G. Trohman

Papers

Prescribing Amiodarone: An Evidence-Based Review of Clinical Indications

Role of prophylactic anticoagulation for direct current cardioversion in patients with atrial fibrillation or atrial flutter

Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes

Chronic Atrial Fibrillation andStroke inPaced Patients WithSickSinusSyndrome Relevance ofClinical Characteristics andPacing Modalities

Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. Relevance of clinical characteristics and pacing modalities.