Rosuvastatin (10 mg daily) did not affect clinical outcomes in patients with chronic heart failure of any cause, in whom the drug seemed to be safe, but a simple fish oil supplement benefitted these patients according to results from the GISSI-HF trial presented at the European Society of Cardiology Congress 2008.

Large observational studies, small prospective studies and post-hoc analyses of randomized clinical trials have suggested that statins could be beneficial in patients with chronic heart failure. However, previous randomized controlled trials have been methodologically weak. This trial investigated the efficacy and safety of the statin rosuvastatin in patients with heart failure.

4,574 patients (mean age 68±11 yr) with chronic heart failure of New York Heart Association class II-IV, irrespective of cause and left ventricular ejection fraction, were included in a double-blind randomized trial testing rosuvastatin 10 mg daily (n=2,285) against placebo (n=2,289). Patients were followed-up for a median of 3.9 years. Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons.

According to the intention to treat analysis, 657 (29%) patients died from any cause in the rosuvastatin group (28.8%) and 644 (28%) in the placebo group (adjusted hazard ratio [HR] 1.00, [95.5% CI 0.898-1.122], p=0.943). No differences were found also with respect to the other primary end-point: 1305 (57%) patients in the rosuvastatin group died or were admitted to hospital for cardiovascular reasons and 1283 (56%) in the placebo group (adjusted HR 1.01, [99% CI [0.908-1.112], p=0.903).

A separate arm of the same study found that a simple fish oil supplement (n-3 PUFA) can benefit patients with heart failure. Several epidemiological and experimental studies suggested that n-3 PUFA could exert favorable effects on the atherotrombotic cardiovascular disease including arrhythmias.

The GISSI researchers enrolled 6,975 patients with chronic heart failure of New York Heart Association class II-IV, assigned to n-3 PUFA 1 g daily or placebo. Patients were followed up for a median of 3.9 years. Primary end-points were time to death and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention-to-treat population.

Among the GISSI findings: 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (relative risk reduction 9%, p=0.041). 1981 (57%) patients in the n-3 PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (relative risk reduction 8%, p=0.009). In absolute terms, 56 patients needed to be treated for 3.9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In a per-protocol analysis performed in about 5000 full complier patients, the relative risk of death was reduced by 14% (p=0.004). Safety was excellent.

GISSI is endorsed by the Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO), Firenze, Italy; Ist.Ricerche Farmacologiche Mario Negri, Milan, Italy and the Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy. The GISSI-HF trial was planned, conducted and analyzed by the GISSI group, which has full ownership of the dat.