Title: Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico–Heart Failure: Rosuvastatin (GISSI-HF: Rosuvastatin Study — Presented at ESC 2008)
Trial Sponsor: Società Prodotti Antibiotici (SPA; Italy), Pfizer, Sigma Tau, and AstraZeneca
Year Presented: 2008
Year Published 2008
Topic(s): General Cardiology, Heart Failure/Transplant
Summary Posted: 8/31/2008
Writer: Anthony A. Bavry, M.D., M.P.H.
Author Disclosure: Consulting Fees/Honoraria: Boston Scientific, Modest (< $10,000); Consulting Fees/Honoraria: Access Closure, Modest (< $10,000)
Reviewer: Deepak L. Bhatt, M.D., F.A.C.C.
Author Disclosure: Research Grants: The Medicines Company, Significant (>= $10,000); Research Grants: Ethicon, Significant (>= $10,000); Research Grants: Bristol Myers Squibb, Significant (>= $10,000); Research Grants: Heartscape, Significant (>= $10,000); Research Grants: Eisai, Significant (>= $10,000); Research Grants: Sanofi Aventis, Significant (>= $10,000)

Description
The goal of this trial was to evaluate the use of rosuvastatin in patients with chronic symptomatic heart failure without a primary indication for statin therapy.
Hypothesis
Among patients with chronic symptomatic heart failure, the use of rosuvastatin will improve cardiac outcomes compared with placebo.
Drugs/Procedures Used
Patients with chronic symptomatic heart failure were randomized to rosuvastatin 10 mg daily (n = 2,285) or placebo (n = 2,289).
Concomitant Medications
Among the participants, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers were used in 94%, beta-blockers in 62%, spironolactone in 40%, diuretics in 90%, and amiodarone in 19%.
Principal Findings
At baseline, 50.7% of participants had an admission for heart failure in the previous year, the mean heart rate was 73 bpm, and the mean systolic blood pressure was 127 mm Hg. The etiology for heart failure was ischemic in 40% and dilated nonischemic in 35%. The rate of medication discontinuation was 34.6% for rosuvastatin versus 36.3% for placebo. The mean low-density lipoprotein cholesterol (LDL-C) at baseline was 57 mg/dl in the rosuvastatin group and 56 mg/dl in the control group. At 3 years, LDL-C had decreased to 42 mg/dl in the rosuvastatin group and stayed the same in the control group (55 mg/dl).

All-cause mortality occurred in 29% of the rosuvastatin group versus 28% of the placebo group (p = 0.94), whereas death or admission to the hospital for cardiovascular reasons occurred in 57% versus 56% (p = 0.90), respectively.

The incidence of cardiac mortality was 20.9% versus 21.3%, sudden cardiac death was 9.6% versus 8.6%, hospitalization for heart failure was 27.5% versus 27.7%, fatal and nonfatal myocardial infarction was 2.7% versus 3.1%, and stroke was 3.6% versus 2.9% (p = not significant for all outcomes), respectively.
Interpretation
The results of this trial demonstrate that rosuvastatin 10 mg daily is not beneficial in reducing cardiac outcomes among patients with chronic symptomatic heart failure. However, rosuvastatin was safe and well tolerated. This finding was somewhat unexpected given the numerous previous trials that documented the benefits of statins.

Possible explanations for the lack of benefit include insufficient follow-up, although this is unlikely since the median follow-up in this study was 3.9 years. Also, it is possible that a different dose of rosuvastatin or a different statin would have produced alternate results. As for the former point, patients already had a low LDL level at baseline. In fact, the 40% of patients with coronary disease were already at optimal goal (i.e., LDL <70 mg/dl). This study should not temper enthusiasm for the use of statins among patients with coronary artery disease; however, it reveals that patients with chronic symptomatic heart failure without a primary indication for lipid reduction do not benefit from this medication.
Conditions
• Heart failure

Therapies
• Medical
• Lipid-lowering agent / HMG CoA Reductase Inhibitor / Rosuvastatin

Study Design
Placebo controlled. Randomized. Blinded. Parallel. Factorial.

Patients Screened: 7,046
Patients Enrolled: 4,631
NYHA Class (% I, II, II, IV): II 62.5%, III 35.0%, IV 2.5%
Mean Follow-Up: median 3.9 years
Mean Patient Age: 68 years
% Female: 23

Mean Ejection Fraction: 33
Primary Endpoints

Time to death
Time to death or admission to hospital for cardiovascular causes
Secondary Endpoints

Cardiovascular mortality
Cardiovascular mortality or all-cause hospital admission
Admission for heart failure, MI or stroke
Patient Population

At least 18 years of age
Chronic symptomatic heart failure
If the ejection fraction was greater than 40%, patient had to be admitted with heart failure at least once in the preceding year
Exclusions:

Contraindication, existing indication or hypersensitivity to study medication
Severe comorbidities precluding follow-up or requiring surgery
Treatment with an investigation agent in the last month
Acute coronary syndrome or cardiac procedure within the preceding month
Planned cardiac surgery within 3 months
Significant liver or renal disease
Pregnant or lactating women or women of childbearing potential who were not adequately protected against pregnancy
References: 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;Aug 31:[Epub ahead of print].

Effects of Rosuvastatin in Patients With Chronic Heart Failure: The GISSI-HF trial. Presented by Dr. Gianni Tognoni at the European Society of Cardiology Congress, Munich, Germany, August/September 2008

Source
Content provided by the American College of Cardiology Foundation