Cardiac Resynchronization Therapy for Patients With Left Ventricular Systolic Dysfunction

Cardiac Resynchronization Therapy for Patients With Left Ventricular Systolic Dysfunction

A Systematic Review

Finlay A. McAlister, MD, MSc; Justin Ezekowitz, MBBCh, MSc; Nicola Hooton, MPH; Ben Vandermeer, MSc; Carol Spooner, BScN, MSc; Donna M. Dryden, PhD; Richard L. Page, MD; Mark A. Hlatky, MD, MPH; Brian H. Rowe, MD, MSc

JAMA. 2007;297:2502-2514.

Context Left ventricular (LV) systolic dysfunction causes substantial morbidity and mortality, even with optimal pharmacotherapy. Atrial-synchronized biventricular pacemakers (cardiac resynchronization therapy [CRT]) received US Food and Drug Administration (FDA) approval for use in selected patients with LV systolic dysfunction in 2001.

Objective To summarize the current evidence base for the efficacy, effectiveness, and safety of CRT in patients with LV systolic dysfunction.

Evidence Acquisition A search of multiple electronic databases until November 2006 was supplemented by hand searches of reference lists of included studies and review articles, proceedings booklets from meetings, FDA reports, and contact with primary study authors and device manufacturers. A total of 14 randomized trials (4420 patients) were included for the CRT efficacy review, 106 studies (9209 patients) for the CRT effectiveness review, and 89 studies (9677 patients) reported safety outcomes with implantation of a CRT device.

Evidence Synthesis All patients in the CRT studies had LV systolic dysfunction (mean LV ejection fraction [LVEF] range, 21%-30%), prolonged QRS duration (mean range, 155-209 milliseconds), and 91% had New York Heart Association (NYHA) class 3 or 4 heart failure symptoms despite optimal pharmacotherapy. CRT improved LVEF (weighted mean difference, 3.0%; 95% confidence interval [CI], 0.9%-5.1%), quality of life (weighted mean reduction in Minnesota Living With Heart Failure Questionnaire, 8.0 points; 95% CI, 5.6-10.4 points), and functional status (improvements of 1 NYHA class were observed in 59% of CRT recipients in the randomized trials). CRT decreased hospitalizations by 37% (95% CI, 7%-57%), and all-cause mortality decreased by 22% (95% CI, 9%-33%). Implant success rate was 93.0% (95% CI, 92.2%-93.7%) and 0.3% of patients died during implantation (95% CI, 0.1%-0.6%). During a median 11-month follow-up, 6.6% (95% CI, 5.6%-7.4%) of CRT devices exhibited lead problems and 5% (95% CI, 4%-7%) malfunctioned.

Conclusions CRT reduces morbidity and mortality in patients with LV systolic dysfunction, prolonged QRS duration, and NYHA class 3 or 4 symptoms when combined with optimal pharmacotherapy. The incremental benefits of combined CRT plus implantable cardioverter-defibrillator devices vs CRT-alone devices in patients with LV systolic dysfunction remain uncertain.

LINK: http://jama.ama-assn.org/cgi/content/short/297/22/2502?rss=1

Aspirin Dose for the Prevention of Cardiovascular Disease - A Systematic Review

Aspirin Dose for the Prevention of Cardiovascular Disease
A Systematic Review

Charles L. Campbell, MD; Susan Smyth, MD, PhD; Gilles Montalescot, MD, PhD; Steven R. Steinhubl, MD

JAMA. 2007;297:2018-2024.

Context More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease, typically either 81 mg/d or 325 mg/d. Controversy remains regarding the most appropriate long-term daily dose.

Objective To review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy, and safety.

Evidence Acquisition A systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included.

Evidence Synthesis Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production, dosages as high as 1300 mg/d are approved for use. In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), followed by 325 mg/d (35%).

The available evidence, predominantly from secondary-prevention observational studies, supports that dosages greater than 75 to 81 mg/d do not enhance efficacy, whereas larger dosages are associated with an increased incidence of bleeding events, primarily related to gastrointestinal tract toxicity.

Conclusions Currently available clinical data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, which may be commonly prescribed, do not better prevent events but are associated with increased risks of gastrointestinal bleeding.

Author Affiliations: Gill Heart Institute, University of Kentucky, Lexington (Drs Campbell, Smyth, and Steinhubl); and Institut de Cardiologie—Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France (Dr Montalescot).


LINKS: http://jama.ama-assn.org/cgi/content/short/297/18/2018?rss=1
JAMA.2007; 297: 2018-2024.