Correspondence
Sudden Death Due to Cardiac Arrhythmias
N Engl J Med 2002; 346:946-947March 21, 2002
- Article
To the Editor:
Spironolactone should be added to Table 2 of the article by Huikuri et al. (Nov. 15 issue)1 as an intervention that may prevent sudden death from cardiac causes. In the Randomized Aldactone Evaluation Study,2 patients with New York Heart Association class III or IV congestive heart failure who were randomly assigned to receive daily spironolactone had a lower risk of sudden death than patients who were randomly assigned to receive placebo (relative risk, 0.71; 95 percent confidence interval, 0.54 to 0.95; P=0.02). Possible mechanisms of this protective effect include potentiation of diuretic-induced hypokalemia as well as neurohormonal interactions.2
2 ReferencesDavid Berlin, M.D.
New York Presbyterian Hospital–Weill Cornell Medical Center, New York, NY 10021
berlind-d@mailcity.com 1
Huikuri HV ,Castellanos A ,Myerburg RJ . Sudden death due to cardiac arrhythmias. N Engl J Med 2001;345:1473-1482
Full Text | Web of Science | Medline2
Pitt B ,Zannad F ,Remme WJ , et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-717
Full Text | Web of Science | Medline
To the Editor:
The interesting review article on sudden death due to cardiac arrhythmias by Huikuri and colleagues did not comment on n–3 fatty acids as useful agents for the primary prevention of sudden death. These naturally occurring compounds are underused in this country and could potentially save thousands of lives each year.
Large, randomized prospective trials have shown that fish1 or fish-oil capsules,2 which provide approximately 1 g of n–3 fatty acids daily, can reduce the risk of sudden death by 50 percent in persons who have had a myocardial infarction. These fatty acids stabilize the electrical activity of cardiac myocytes by inhibiting membrane ion channels and prolonging the relative refractory period.3 They also exert an antiarrhythmic action by increasing heart-rate variability.4
In addition to beta-blockers, n–3 fatty acids should be considered to be accepted therapeutic agents for preventing sudden death in persons who have had a myocardial infarction.
4 ReferencesMark R. Goldstein, M.D.
Riddle Memorial Hospital, Media, PA 19063
mrgolds@aol.com 1
Burr ML ,Gilbert JF ,Holliday RM , et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and Reinfarction Trial (DART). Lancet 1989;334:757-761
CrossRef2
GISSI-Prevenzione Investigators
CrossRef | Web of Science | Medline3
Kang JX ,Leaf A . Antiarrhythmic effects of polyunsaturated fatty acids: recent studies. Circulation 1996;94:1774-1780
Web of Science | Medline4
Christensen JH ,Gustenhoff P ,Korup E , et al. Effect of fish oil on heart rate variability in survivors of myocardial infarction: a double blind randomised controlled trial. BMJ 1996;312:677-678
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. Berlin suggests that spironolactone and Dr. Goldstein proposes that n–3 fatty acids should be included on the list of accepted therapeutic agents for preventing sudden death from cardiac causes. Indeed, two randomized trials have shown that fish1 or fish-oil capsules2 can reduce the risk of the combined end point of death, myocardial infarction, and stroke among patients with a prior myocardial infarction. In the Randomized Aldactone Evaluation Study,3 spironolactone lowered the risk of death among patients with heart failure. Subanalyses of the results of these trials have also suggested that both n–3 fatty acids and spironolactone may reduce the risk of sudden death.
Despite these promising results, there are some shortcomings in the designs of these trials that prevent the generalization of the concept that these agents have a definite role in the primary prevention of sudden death from arrhythmia. First, none of these trials included sudden death from cardiac causes as a primary end point, and therefore, the studies were not powered accordingly. Second, there were no prespecified definitions of sudden death from cardiac causes in any of these trials, and only one end-point committee defined the mode of death. In fact, a recent beta-blocker study4 was the first drug trial that paid specific attention to the definition of sudden death from cardiac causes. On the basis of the results of that trial and concordant information from a subanalysis of several other beta-blocker trials, we concluded that only in the case of beta-blocking drugs was there sufficient evidence to warrant their inclusion as a recommended treatment for the primary prevention of sudden death from cardiac causes.
Definitive evidence from prospective trials should be a requirement before any therapeutic strategy is widely recommended and accepted. Any new preventive strategies that can decrease the worldwide problem of sudden death from cardiac causes will be welcomed, but the overall and individual effects5 must first be proved by means of carefully planned and executed clinical trials.
5 ReferencesHeikki V. Huikuri, M.D.
University of Oulu, FIN-90029 Oulu, Finland
heikki.huikuri@oulu. fi Agustin Castellanos, M.D.
Robert J. Myerburg, M.D.
University of Miami School of Medicine, Miami, FL 331011
Burr ML ,Gilbert JF ,Holliday RM , et al. Effects of changes in fat, fish, and fiber intakes on death and myocardial reinfarction: Diet and Reinfarction Trial (DART). Lancet 1989;334:757-761
CrossRef2
GISSI-Prevenzione Investigators
CrossRef | Web of Science | Medline3
Pitt B ,Zannad F ,Remme WJ , et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-717
Full Text | Web of Science | Medline4
Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001-2007
CrossRef | Web of Science | Medline5
Myerburg RJ ,Mitrani R ,Interian A Jr ,Castellanos A . Interpretation of outcomes of antiarrhythmic clinical trials: design features and population impact. Circulation 1998;97:1514-1521
Web of Science | Medline
