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Title: No Efficacy Benefits Seen With Rosuvastatin Against Placebo in GISSI-HF Trial of Symptomatic Chronic Heart Failure: Presented at ESC

"No Efficacy Benefits Seen With Rosuvastatin Against Placebo in GISSI-HF Trial of Symptomatic Chronic Heart Failure: Presented at ESC"

By Chris Berrie MUNICH, Germany -- September 2, 2008 -- Rosuvastatin 10 mg daily shows a good safety profile but no benefit over placebo for patients with chronic heart failure (CHF) of any age, aetiology, or systolic function, according to a multicentre, randomised, placebo-controlled trial presented here at the European Society of Cardiology 2008 Congress (ESC 2008). A number of randomised clinical trials (RCTs) and meta-analyses have suggested that statins provide reductions in cardiovascular mortality in patients with HF of both ischaemic and nonischaemic aetiologies. However, the need remained for large-scale RCTs to assess efficacy and verify safety in patients at specific renal and hepatic risk, said Gianni Tognoni, MD, Consorzio Mario Negri Sud Research Institute, Santa Maria Imbaro, Italy, who presented the results on behalf of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI) study investigators on August 31. To achieve this goal, the full heart failure nested trial (GISSI-HF) enrolled patients aged 18 years and older with a diagnosis of with chronic symptomatic CHF of any aetiology and with any left ventricular ejection fraction (LVEF). For the rosuvastatin part of the study, exclusion criteria included severe comorbidities and acute coronary syndrome or a cardiac procedure within the preceding month, plus previous statin treatment or contraindications to statins. The 4,574 patients enrolled were randomised to either placebo (n = 2,289) or rosuvastatin 10 mg daily (n = 2,285). Demographic characteristics, medical histories, and disease aetiologies across the placebo and rosuvastatin groups showed no significant differences. Concomitant medical treatments were well matched, with at least 90% on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and diuretics and two-thirds on beta-blockers. At a median follow-up of 3.9 years, the researchers found no difference in results for time to all-cause mortality, Dr. Tognoni said, with 28.1% for placebo and 28.8% for rosuvastatin and an adjusted hazard ratio (aHR) of 1.00 ([P = .943). All-cause mortality or hospitalisation for cardiovascular reasons also showed no difference, at 56.1% and 57.1%, respectively (aHR, 1.01; P = .903).

Similarly, the full range of secondary end-points and predefined subgroup analyses showed no significant effects for rosuvastatin.

As expected for statins, levels of low-density lipoprotein (LDL) cholesterol were significantly reduced with rosuvastatin compared with placebo. LDL levels at year 1 were 83 and 130 mg/dL, respectively (P < .0001), and at year 3 they were 89 and 118 mg/dL, respectively (P < .0001). Similarly, a significantly larger decrease in high-sensitivity C-reactive protein levels was seen over the first 3 months of treatment (0.45 vs 0.10 mg/L, respectively; P = .0195).

Permanent treatment discontinuations and range of adverse drug reactions were not significantly different across treatment groups.

While he noted that "there was a clear dissociation between the pharmacological effect and the absence of a clinical effect," Dr. Tognoni stressed that "the safety data are reassuring, making the likelihood of [rosuvastatin] causing harm, suggested in previous reports, at least remote."

Funding for this study was provided by SPA, Pfizer, Sigma Tau, and AstraZeneca. The results were published simultaneously online in The Lancet (DOI:10.1016/S0140-6736(08)61240-4).

[Presentation title: Effects of Statins in Patients With Symptomatic Chronic Heart Failure: The GISSI-HF Results. Hot Line I. Abstract 236]

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