GISSI-HF- Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic CHF

Summary

INTRODUCTION While pharmacological treatments specifically targeted to the cardio-circulatory system have been largely investigated, scanty controlled data are available concerning the role of dietary and metabolic approaches in the management/outcome of patients with heart failure. A large scale, randomized, clinical trial is proposed to test the effects of (a) n-3 PUFA and (b) a lipid lowering agent on top of the best recommended treatments for heart failure. STUDY DESIGN The GISSI-HF is a prospective, multicenter, randomized, double blind, placebo controlled study, with randomized allocation of patients with a clinical diagnosis of heart failure to: Randomization 1 (R1): n-3 PUFA 1 g daily vs corresponding placebo; Randomization 2 (R2): rosuvastatin 10 mg daily vs corresponding placebo. OBJECTIVES OF THE STUDY PRIMARY OBJECTIVES To demonstrate that, in patients with heart failure treated at the best of recommended therapies, long term administration of (a) n-3 PUFA, (b) rosuvastatin is more effective than the corresponding placebo in the reduction of: * All-cause mortality * All-cause mortality or hospitalizations for cardiovascular reason OTHER END-POINT MEASURES OF EFFICACY To assess that long term administration of (a) n-3 PUFA, (b) rosuvastatin is more effective than corresponding placebo in the reduction of: * Cardiovascular mortality * Cardiovascular mortality or hospitalizations for any reason * Sudden cardiac death * Hospitalizations for any reason * Hospitalizations for cardiovascular reasons * Hospitalizations for congestive heart failure * Myocardial infarction * Stroke

Timeline

Start

2002-08

Primary completion

2008-04

Completion

2008-05

Publications

• Background Tavazzi L, Tognoni G, Franzosi MG, Latini R, Maggioni AP, Marchioli R, Nicolosi GL, Porcu M; GISSI-HF Investigators. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail. 2004 Aug;6(5):635-41. doi: 10.1016/j.ejheart.2004.03.001.
• Results Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G; Gissi-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Oct 4;372(9645):1223-30. doi: 10.1016/S0140-6736(08)61239-8. Epub 2008 Aug 29.
• Results Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G; Gissi-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Oct 4;372(9645):1231-9. doi: 10.1016/S0140-6736(08)61240-4. Epub 2008 Aug 29.
• Canepa M, Ameri P, Lucci D, Nicolosi GL, Marchioli R, Porcu M, Tognoni G, Franzosi MG, Latini R, Maseri A, Tavazzi L, Maggioni AP; GISSI-HF Investigators. Modes of death and prognostic outliers in chronic heart failure. Am Heart J. 2019 Feb;208:100-109. doi: 10.1016/j.ahj.2018.11.009. Epub 2018 Nov 24.
• Mantovani A, Targher G, Temporelli PL, Lucci D, Gonzini L, Nicolosi GL, Marchioli R, Tognoni G, Latini R, Cosmi F, Tavazzi L, Maggioni AP; GISSI-HF Investigators. Prognostic impact of elevated serum uric acid levels on long-term outcomes in patients with chronic heart failure: A post-hoc analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial. Metabolism. 2018 Jun;83:205-215. doi: 10.1016/j.metabol.2018.02.007. Epub 2018 Mar 29.
• Dauriz M, Targher G, Temporelli PL, Lucci D, Gonzini L, Nicolosi GL, Marchioli R, Tognoni G, Latini R, Cosmi F, Tavazzi L, Maggioni AP; GISSI-HF Investigators. Prognostic Impact of Diabetes and Prediabetes on Survival Outcomes in Patients With Chronic Heart Failure: A Post-Hoc Analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) Trial. J Am Heart Assoc. 2017 Jul 5;6(7):e005156. doi: 10.1161/JAHA.116.005156.
• Rossi A, Inciardi RM, Rossi A, Temporelli PL, Lucci D, Gonzini L, Marchioli R, Nicolosi GL, Tavazzi L; GISSI-HF Investigators. Prognostic effects of rosuvastatin in patients with co-existing chronic obstructive pulmonary disease and chronic heart failure: A sub-analysis of GISSI-HF trial. Pulm Pharmacol Ther. 2017 Jun;44:16-23. doi: 10.1016/j.pupt.2017.03.001. Epub 2017 Mar 3.
• Florea VG, Rector TS, Anand IS, Cohn JN. Heart Failure With Improved Ejection Fraction: Clinical Characteristics, Correlates of Recovery, and Survival: Results From the Valsartan Heart Failure Trial. Circ Heart Fail. 2016 Jul;9(7):e003123. doi: 10.1161/CIRCHEARTFAILURE.116.003123.
• Damman K, Masson S, Hillege HL, Voors AA, van Veldhuisen DJ, Rossignol P, Proietti G, Barbuzzi S, Nicolosi GL, Tavazzi L, Maggioni AP, Latini R. Tubular damage and worsening renal function in chronic heart failure. JACC Heart Fail. 2013 Oct;1(5):417-24. doi: 10.1016/j.jchf.2013.05.007. Epub 2013 Sep 11.
• Barlera S, Tavazzi L, Franzosi MG, Marchioli R, Raimondi E, Masson S, Urso R, Lucci D, Nicolosi GL, Maggioni AP, Tognoni G; GISSI-HF Investigators. Predictors of mortality in 6975 patients with chronic heart failure in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure trial: proposal for a nomogram. Circ Heart Fail. 2013 Jan;6(1):31-9. doi: 10.1161/CIRCHEARTFAILURE.112.967828. Epub 2012 Nov 14.
• La Rovere MT, Pinna GD, Maestri R, Barlera S, Bernardinangeli M, Veniani M, Nicolosi GL, Marchioli R, Tavazzi L; GISSI-HF Investigators. Autonomic markers and cardiovascular and arrhythmic events in heart failure patients: still a place in prognostication? Data from the GISSI-HF trial. Eur J Heart Fail. 2012 Dec;14(12):1410-9. doi: 10.1093/eurjhf/hfs126. Epub 2012 Jul 30.
• Latini R, Gullestad L, Masson S, Nymo SH, Ueland T, Cuccovillo I, Vardal M, Bottazzi B, Mantovani A, Lucci D, Masuda N, Sudo Y, Wikstrand J, Tognoni G, Aukrust P, Tavazzi L; Investigators of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) and GISSI-Heart Failure (GISSI-HF) trials. Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials. Eur J Heart Fail. 2012 Sep;14(9):992-9. doi: 10.1093/eurjhf/hfs092. Epub 2012 Jun 27.
• Masson S, Anand I, Favero C, Barlera S, Vago T, Bertocchi F, Maggioni AP, Tavazzi L, Tognoni G, Cohn JN, Latini R; Valsartan Heart Failure Trial (Val-HeFT) and Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) Investigators. Serial measurement of cardiac troponin T using a highly sensitive assay in patients with chronic heart failure: data from 2 large randomized clinical trials. Circulation. 2012 Jan 17;125(2):280-8. doi: 10.1161/CIRCULATIONAHA.111.044149. Epub 2011 Dec 2.
• Damman K, Masson S, Hillege HL, Maggioni AP, Voors AA, Opasich C, van Veldhuisen DJ, Montagna L, Cosmi F, Tognoni G, Tavazzi L, Latini R. Clinical outcome of renal tubular damage in chronic heart failure. Eur Heart J. 2011 Nov;32(21):2705-12. doi: 10.1093/eurheartj/ehr190. Epub 2011 Jun 11.
• Finzi AA, Latini R, Barlera S, Rossi MG, Ruggeri A, Mezzani A, Favero C, Franzosi MG, Serra D, Lucci D, Bianchini F, Bernasconi R, Maggioni AP, Nicolosi G, Porcu M, Tognoni G, Tavazzi L, Marchioli R. Effects of n-3 polyunsaturated fatty acids on malignant ventricular arrhythmias in patients with chronic heart failure and implantable cardioverter-defibrillators: A substudy of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) trial. Am Heart J. 2011 Feb;161(2):338-343.e1. doi: 10.1016/j.ahj.2010.10.032.
• Maggioni AP, Fabbri G, Lucci D, Marchioli R, Franzosi MG, Latini R, Nicolosi GL, Porcu M, Cosmi F, Stefanelli S, Tognoni G, Tavazzi L; GISSI-HF Investigators. Effects of rosuvastatin on atrial fibrillation occurrence: ancillary results of the GISSI-HF trial. Eur Heart J. 2009 Oct;30(19):2327-36. doi: 10.1093/eurheartj/ehp357. Epub 2009 Aug 30.

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