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The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure

Open access
Packer, Milton, Carver, Joseph R., Rodeheffer, Richard J., Ivanhoe, Russell J., DiBianco, Robert, Zeldis, Steven M., Hendrix, Grady H., Bommer, William J., Elkayam, Uri, Kukin, Marrick L., Mallis, George I., Sollano, Josephine A., Shannon, James, Tandon, P.K., DeMets, David L.·1991·New England Journal of Medicine
DOI 10.1056/nejm199111213252103
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Abstract

BACKGROUND: Milrinone, a phosphodiesterase inhibitor, enhances cardiac contractility by increasing intracellular levels of cyclic AMP, but the long-term effect of this type of positive inotropic agent on the survival of patients with chronic heart failure has not been determined. METHODS: We randomly assigned 1,088 patients with severe chronic heart failure (New York Heart Association class III or IV) and advanced left ventricular dysfunction to double-blind treatment with (40 mg of oral milrinone daily (561 patients) or placebo (527 patients). In addition, all patients received conventional therapy with digoxin, diuretics, and a converting-enzyme inhibitor throughout the trial. The median period of follow-up was 6.1 months (range, 1 day to 20 months). RESULTS: As compared with placebo, milrinone therapy was associated with a 28 percent increase in mortality from all causes (95 percent confidence interval, 1 to 61 percent; P = 0.038) and a 34 percent increase in cardiovascular mortality (95 percent confidence interval, 6 to 69 percent; P = 0.016). The adverse effect of milrinone was greatest in patients with the most severe symptoms (New York Heart Association class IV), who had a 53 percent increase in mortality (95 percent confidence interval, 13 to 107 percent; P = 0.006). Milrinone did not have a beneficial effect on the survival of any subgroup. Patients treated with milrinone had more hospitalizations (44 vs. 39 percent, P = 0.041), were withdrawn from double-blind therapy more frequently (12.7 vs. 8.7 percent, P = 0.041), and had serious adverse cardiovascular reactions, including hypotension (P = 0.006) and syncope (P = 0.002), more often than the patients given placebo. CONCLUSIONS: Our findings indicate that despite its beneficial hemodynamic actions, long-term therapy with oral milrinone increases the morbidity and mortality of patients with severe chronic heart failure. The mechanism by which the drug exerts its deleterious effects is unknown.

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Metadata

Authors
Packer, M., Carver, J. R., Rodeheffer, R. J., Ivanhoe, R. J., DiBianco, R., Zeldis, S. M., Hendrix, G. H., Bommer, W. J., Elkayam, U., Kukin, M. L., Mallis, G. I., Sollano, J. A., Shannon, J., Tandon, P. K., & DeMets, D. L.
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1991-11-21
Volume
325
Issue
21
Pages
1468-1475
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199111213252103
OpenAlex
W2319534362
Cited by
2,225
References
3
FWCI
55.09
Type
journal article
Language
en
Open access
bronze

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