Rosuvastatin is Not Beneficial Among Patients with Chronic Heart Failure: Results from GISSI-HF trial

August 31, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

ESC 2008-Munich, Germany: The GISSI-HF trial does not demonstrate an improvement in cardiovascular death or hospitalization associated with Rosuvastatin administration among patients with chronic heart failure.

Statins are also speculated to have anti-inflammatory, antihypertrophic, antifibrotic and antioxidant effects in addition to their cholesterol lowering effects. Furthermore they also improve endothelial function, inhibit neurohumoral activation and prevent cardiac arrhythmias. Given role of neurohormonal regulation in the pathophysiology of heart failure, previous studies have suggested that statins might be beneficial among patients with chronic heart failure. The investigators of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nell’Insuffi cienza cardiaca) trial investigated this further to determine if the use of rosuvastatin compared with placebo would reduce the incidence of death and hospitalizations due to cardiovascular causes. This study was double blinded, randomized and placebo controlled from 326 cardiology centers and 31 internal medicine centers in Italy.

The data was presented by Dr. Gianni Tognoni of Italy at the European Society of Cardiology Congress 2008 in Munich, Germany with commentary by Professor Philip-Poole-Wilson of United Kingdom and simultaneously published in the Lancet today.

A total of 4574 patients with chronic heart failure belonging to NYHA class II-IV aged 18 years and over were included in the trial irrespective of their baseline left ventricular ejection fraction (LVEF). Patients were randomized to receive rosuvastatin 10 mg once daily (n=2285) or placebo (n=2289). The primary endpoint consisted of time to death, and time to death or admission to hospital for cardiovascular causes. The median duration of follow-up was 3.9 years (Inter-quartile range 3-4.4 years). The mean baseline LVEF (SD) was 33.4% (8.8) vs. 33.1% (8.7) in the rosuvastatin and placebo groups respectively.

The mean age of study patients was 68 ± 11 years. The LDL cholesterol decreased from 3.16 mmol/L at baseline to 2.15 mmol/L after one year and 2.31 mmol/L after 3 years among patients in the rosuvastatin group while no change in LDL cholesterol was observed in the placebo group from baseline (3.13 mmol/L) and after 1 year (3.37 mmol/L) and 3 years (3.06 mmol/L), [interaction time vs. treatment, p<0.0001]. Rosuvastatin also reduced high sensitivity CRP levels over 3 months compared with the placebo group (p=0.0195).

The main findings of this trial are as follows: in the intention to treat analysis, there was no difference in the occurrence of death from any cause in the rosuvastatin and placebo groups [29% vs. 28% [adjusted HR 1.00, (95.5% confidence interval 0.898-1.122, p=0.943). There was also no significant difference between the rosuvastatin and placebo groups in the occurrence of death or hospitalizations for cardiovascular causes [57% vs. 56% adjusted HR 1.01 (99% CI 0.908-1.112), p=0.903].

Likewise, there was no significant difference in the incidence of discontinuation of the drug due to adverse events in both groups (Rosuvastatin 4.6% vs. placebo 4%, p=0.36) and gastrointestinal disorders were reported equally in both groups (rosuvastatin 1% vs. 2% placebo).

The investigators of this trial concluded that among patients with chronic heart failure the use of rosuvastatin was not beneficial in reducing death or hospital admissions due to cardiovascular causes and thus cannot be recommended for non-ischemic patients with chronic heart failure. Furthermore, this study supports the observations in the CORONA trial regarding the lack of benefit of statins among heart failure patients. The CORONA study consisted of 5011 patients. .

The limitations that are to be taken into consideration with this trial include the fact that only one dose of rosuvastatin (10 mg) was used in this study. Only 10% of the patients had LVEF >40%, hence the applicability of the results of this in this group of patients is not known. Furthermore there were only 24% of patients who were women in this trial and the baseline LDL level was 3.16 mmol/L. Again the applicability of this trial results among women and patients with elevated baseline LDL levels is uncertain.

The GISSI-HF trial is supported by: Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO), Firenze, Italy; Ist.Ricerche Farmacologiche Mario Negri, Milan, Italy; Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.

This study was funded by SPA, Pfizer, Sigma Tau and AstraZeneca.

Reviewed by C. Michael Gibson, M.S., M.D.

Source

 * 1) http://www.escardio.org/congresses/esc2008/congress-reports/Pages/236-237-tognoni-poole-wilson.aspx
 * 2) http://www.thelancet.com/journals/eop