Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial.

J. Lubsen, H. Just, A. C. Hjalmarsson, D. La Framboise, W. J. Remme, J. Heinrich-Nols, J. M. Dumont, P. Seed

London School of Hygiene and Tropical Medicine, UK.

PRIMARY OBJECTIVE: To determine the effects of pimobendan 2.5 and 5 mg daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, placebo controlled trial of the addition of pimobendan to conventional treatment with a minimum follow up of 24 weeks. SETTING: Outpatient cardiology clinics in six European countries. PATIENTS: 317 patients with stable symptomatic heart failure, objectively impaired exercise capacity, and an ejection fraction of 45% or lower who were treated with at least an angiotensin converting enzyme inhibitor and a diuretic and who tolerated a test dose of pimobendan. RESULTS: Compared with placebo, both pimobendan 2.5 and 5 mg daily improved exercise duration (bicycle ergometry) by 6% (P = 0.03 and 0.05) after 24 weeks of treatment. At that time 63% of patients allocated to pimobendan and 59% of those allocated to placebo were alive and able to exercise to at least the same level as at entry (P = 0.5). No significant effects on oxygen consumption (assessed in a subgroup of patients) and on quality of life (assessed by questionnaire) were observed. Pimobendan was well tolerated. Proarrhythmic effects (24-hour electrocardiography) were not observed. In both pimobendan groups combined the hazard of death was 1.8 (95% confidence interval 0.9 to 3.5) times higher than in the placebo group. CONCLUSIONS: Pimobendan improves exercise capacity in patients with chronic heart failure who are also on conventional treatment. The balance between benefit and risk of treatment with this compound remains to be established however.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., Jessup, M., Konstam, M. A., Mancini, D. M., Michl, K., Oates, J. A., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W. (2009). 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 53: e1-e90 [Full Text]  
• Jessup, M., Abraham, W. T., Casey, D. E., Feldman, A. M., Francis, G. S., Ganiats, T. G., Konstam, M. A., Mancini, D. M., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W. (2009). 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 53: 1343-1382 [Full Text]  
• 2009 WRITING GROUP TO REVIEW NEW EVIDENCE AND UPDA, , Jessup, M., Abraham, W. T., Casey, D. E., Feldman, A. M., Francis, G. S., Ganiats, T. G., Konstam, M. A., Mancini, D. M., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W. (2009). 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation. Circulation 119: 1977-2016 [Full Text]  
• 2005 WRITING COMMITTEE MEMBERS, , Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., Jessup, M., Konstam, M. A., Mancini, D. M., Michl, K., Oates, J. A., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W. (2009). 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation. Circulation 119: e391-e479 [Full Text]  
• Keweloh, B., Janssen, P. M.L., Siegel, U., Datz, N., Zeitz, O., Hermann, H.-P. (2007). Influence of pyruvate on economy of contraction in isolated rabbit myocardium. Eur J Heart Fail 9: 754-761 [Abstract] [Full Text]  
• Kass, D. A., Solaro, R. J. (2006). Mechanisms and Use of Calcium-Sensitizing Agents in the Failing Heart. Circulation 113: 305-315 [Full Text]  
• Sackner-Bernstein, J. D., Kowalski, M., Fox, M., Aaronson, K. (2005). Short-term Risk of Death After Treatment With Nesiritide for Decompensated Heart Failure: A Pooled Analysis of Randomized Controlled Trials. JAMA 293: 1900-1905 [Abstract] [Full Text]  
• Yan, A. T., Yan, R. T., Liu, P. P. (2005). Narrative Review: Pharmacotherapy for Chronic Heart Failure: Evidence from Recent Clinical Trials. ANN INTERN MED 142: 132-145 [Abstract] [Full Text]  
• Poder, P., Eha, J., Sundberg, S., Antila, S., Heinpalu, M., Loogna, I., Planken, U., Rantanen, S., Lehtonen, L. (2004). Pharmacodynamics and Pharmacokinetics of Oral Levosimendan and Its Metabolites in Patients With Severe Congestive Heart Failure: A Dosing Interval Study. J Clin Pharmacol 44: 1143-1150 [Abstract] [Full Text]  
• Zanolla, L., Zardini, P. (2003). Selection of endpoints for heart failure clinical trials. Eur J Heart Fail 5: 717-723 [Abstract] [Full Text]  
• Greenberg, B., Borghi, C., Perrone, S. (2003). Pharmacotherapeutic approaches for decompensated heart failure: a role for the calcium sensitiser, levosimendan?. Eur J Heart Fail 5: 13-21 [Abstract] [Full Text]  
• Al-Hesayen, A., Azevedo, E. R., Newton, G. E., Parker, J. D. (2002). The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure. J Am Coll Cardiol 39: 1269-1274 [Abstract] [Full Text]  
• Swynghedauw, B, Charlemagne, D (2002). What is wrong with positive inotropic drugs? Lessons from basic science and clinical trials. Eur Heart J Suppl 4: D43-D49 [Abstract]  
• van Veldhuisen, D. J. (2002). Low-dose digoxin in patients with heart failure: Less toxic and at least as effective?. J Am Coll Cardiol 39: 954-956 [Full Text]  
• Lowes, B. D., Higginbotham, M., Petrovich, L., DeWood, M. A., Greenberg, M. A., Rahko, P. S., Dec, G. W., LeJemtel, T. H., Roden, R. L., Schleman, M. M., Robertson, A. D., Gorczynski, R. J., Bristow, M. R., for the Enoximone Study Group, (2000). Low-dose enoximone improves exercise capacity in chronic heart failure. J Am Coll Cardiol 36: 501-508 [Abstract] [Full Text]  
• Cohn, J. N., Ferrari, R., Sharpe, N., on Behalf of an International Forum on Cardiac Rem, (2000). Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol 35: 569-582 [Abstract] [Full Text]  
• Coodley, E. (1999). Newer Drug Therapy for Congestive Heart Failure. Arch Intern Med 159: 1177-1183 [Abstract] [Full Text]  
• The Investigators of the Study on Propionyl-L-Carn, (1999). Study on propionyl-L-carnitine in chronic heart failure. Eur Heart J 20: 70-76 [Abstract]  
• Gheorghiade, M., Bonow, R. O. (1998). Chronic Heart Failure in the United States : A Manifestation of Coronary Artery Disease. Circulation 97: 282-289 [Full Text]  
• (1996). Pimobendan Disappointing for Heart Failure. Journal Watch Cardiology 1996: 5-5 [Full Text]