title: Dronedarone for atrial fibrillation: the limited reliability of clinical practice guidelines.
abstract: Concerns have been expressed about the reliability of clinical practice guidelines. We analyzed 3 guidelines from medical specialty societies about dronedarone hydrochloride, an antiarrhythmic drug related to amiodarone hydrochloride, for treatment of patients with atrial fibrillation. We compared the recommendations in these guidelines with the conclusions about dronedarone that we reached by applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Method to the same evidence base. In our analysis, as a rate control drug, dronedarone was better than placebo only for a surrogate outcome (heart rate). As a rhythm control drug, dronedarone was associated with 13 (95% CI, -15 to 61) excess deaths per 1000 patients treated as compared with placebo. Compared with amiodarone, dronedarone was less effective (214 [95% CI, 130 to 294] more recurrences of atrial fibrillation per 1000 patients treated) and similarly tolerated (-28 [95% CI, -69 to 33] more serious adverse events requiring drug suspension per 1000 patients treated). Despite the limits of the evidence, all 3 guidelines recommended dronedarone for prevention of recurrences of atrial fibrillation; 2 of the guidelines recommended it as a rate control agent. Our findings raise questions about the reliability of these clinical practice guidelines, as well as the financial associations between many of the panel members and the manufacturer of dronedarone.
authors.affiliation: Emergency Department, Tigullio Hospital, Lavagna, Italy.
authors.forename: Primiano
authors.initials: P
authors.lastname: Iannone
authors.affiliation: Emergency Department, Tigullio Hospital, Lavagna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Haupt
authors.affiliation: Liguria Health Technology Assessment Network, Genova, Italy.
authors.forename: Gaddo
authors.initials: G
authors.lastname: Flego
authors.affiliation: Emergency Department, Tigullio Hospital, Lavagna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Truglio
authors.affiliation: Emergency Department, Frimley Park Hospital, Frimley, England.
authors.forename: Monica
authors.initials: M
authors.lastname: Minardi
authors.affiliation: Emergency Department, Frimley Park Hospital, Frimley, England.
authors.forename: Simon
authors.initials: S
authors.lastname: Clarke
authors.affiliation: Drug Evaluation Unit, World Health Organization Collaborating Centre in Evidence-Based Research Synthesis and Guideline Development, Emilia Romagna Health and Social Care Agency, Bologna, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Magrini
mesh_terms: D000638:Amiodarone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D002170:Canada; D000077764:Dronedarone; D019317:Evidence-Based Medicine; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D017410:Practice Guidelines as Topic; D012008:Recurrence; D015203:Reproducibility of Results; D014481:United States
chemical_list: D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone