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Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure.
J Am Coll Cardiol 1998; 31(6):1336-40JACC

Abstract

OBJECTIVES

We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure.

BACKGROUND

Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade.

METHODS

Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2+/-1.2%, cardiac index 1.6+/-0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of < or = 1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day.

RESULTS

Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4+/-1.8 months. The mean length of follow-up was 20.9+/-3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7+/-1.6% to 27.6+/-3.4% (p=0.01), whereas the New York Heart Association functional class improved from 4+/-0 to 2.8+/-0.1 (p=0.0001). The number of hospital admissions tended to decrease during therapy (p=0.06). The estimated probability of survival at 1 year was 81+/-9%. Heart transplantation was performed successfully in nine patients (30%).

CONCLUSIONS

Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is warranted.

Authors+Show Affiliations

Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study

Language

eng

PubMed ID

9581729

Citation

Shakar, S F., et al. "Combined Oral Positive Inotropic and Beta-blocker Therapy for Treatment of Refractory Class IV Heart Failure." Journal of the American College of Cardiology, vol. 31, no. 6, 1998, pp. 1336-40.
Shakar SF, Abraham WT, Gilbert EM, et al. Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure. J Am Coll Cardiol. 1998;31(6):1336-40.
Shakar, S. F., Abraham, W. T., Gilbert, E. M., Robertson, A. D., Lowes, B. D., Zisman, L. S., ... Bristow, M. R. (1998). Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure. Journal of the American College of Cardiology, 31(6), pp. 1336-40.
Shakar SF, et al. Combined Oral Positive Inotropic and Beta-blocker Therapy for Treatment of Refractory Class IV Heart Failure. J Am Coll Cardiol. 1998;31(6):1336-40. PubMed PMID: 9581729.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure. AU - Shakar,S F, AU - Abraham,W T, AU - Gilbert,E M, AU - Robertson,A D, AU - Lowes,B D, AU - Zisman,L S, AU - Ferguson,D A, AU - Bristow,M R, PY - 1998/5/15/pubmed PY - 1998/5/15/medline PY - 1998/5/15/entrez SP - 1336 EP - 40 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 31 IS - 6 N2 - OBJECTIVES: We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. BACKGROUND: Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. METHODS: Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2+/-1.2%, cardiac index 1.6+/-0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of < or = 1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. RESULTS: Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4+/-1.8 months. The mean length of follow-up was 20.9+/-3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7+/-1.6% to 27.6+/-3.4% (p=0.01), whereas the New York Heart Association functional class improved from 4+/-0 to 2.8+/-0.1 (p=0.0001). The number of hospital admissions tended to decrease during therapy (p=0.06). The estimated probability of survival at 1 year was 81+/-9%. Heart transplantation was performed successfully in nine patients (30%). CONCLUSIONS: Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is warranted. SN - 0735-1097 UR - https://www.unboundmedicine.com/medline/citation/9581729/Combined_oral_positive_inotropic_and_beta_blocker_therapy_for_treatment_of_refractory_class_IV_heart_failure_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(98)00077-1 DB - PRIME DP - Unbound Medicine ER -