Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico–Heart Failure: Rosuvastatin - GISSI-HF: Rosuvastatin Study

Aug 31, 2008
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Trial Sponsor:
Società Prodotti Antibiotici (SPA; Italy), Pfizer, Sigma Tau, and AstraZeneca
Date Presented:
01/01/2008
Date Published:
01/01/2008
Date Updated:
08/31/2008
Original Posted Date:
08/31/2008
References

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.

Study Design

Patients Screened: 7,046
Patients Enrolled: 4,631
NYHA Class: 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

Patient Populations:

  • 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

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

Drug/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.="" 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="">

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.

Keywords: Fluorobenzenes, Stroke, Myocardial Infarction, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Coronary Disease, Pyrimidines, Blood Pressure, Heart Rate, Lipoproteins, LDL, Heart Failure, Hospitalization, Death, Sudden, Cardiac, Sulfonamides


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