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: Early Online Publication, 31 August 2008
http://www.thelancet.com/journals/lancet/article/PIIS0140673608612404/abstract
GISSI-HF investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; Early Online Publication, 31 August 2008
http://www.thelancet.com/journals/lancet/article/PIIS0140673608612398/abstract
Fonarow GC. Statins and n-3 fatty acid supplementation in heart failure. Lancet 2008; Published online Aug. 31. (Editorial)
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ESC: European Society of Cardiology Congress Meeting
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ESC: Statin Flops While Fish Oil Supplement Floats in Chronic Heart Failure
By Peggy Peck, Executive Editor, MedPage Today
Published: August 31, 2008
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
Action Points ÂÂ
• Explain to interested patients that this study suggests that a daily intake of omega-3 fatty acid supplement for close to four years may provide a slight reduction in mortality or hospitalizations for patients with chronic heart failure.
• Explain to interested patients that this study suggests treatment with statins does not appear to be beneficial in patients with chronic heart failure.
MUNICH, Aug. 31 -- A fish oil capsule atop standard therapy for chronic heart failure significantly reduced mortality and hospital admissions whereas a potent statin had no comparable benefits, researchers reported here.
The absolute reduction in mortality for patients taking omega-3 fatty acid supplement (1 g/day) for an average of four years was just 1.8%, but that resulted in a statistically significant reduction in relative risk (P=0.04), said Luigi Tavazzi, M.D., of GVM Hospitals of Care and Research in Cotignola, Italy, and chairman of the multicenter GISSI-HF trial.
By contrast, heart failure patients who received 10 mg/day of rosuvastatin (Crestor) atop standard therapy did no better than placebo patients. The implication was clear, said Gianni Tognoni, M.D., of Consorzio Mario Negri Stud, S. Maria Imbaro, Italy, and co-chair of GISSI-HF. Although statins have demonstrated efficacy in coronary artery disease, "they have no role in heart failure."
Drs. Tavazzi and Tognoni reported the results of the twinned GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico) heart failure studies at the European Society of Cardiology meeting. The results were simultaneously published online by The Lancet.
The benefit seen with n-3 polyunsaturated fatty acids was about 9%, and while that was good enough to meet the primary endpoint it was short of the 15% benefit that had been expected, Dr. Tavazzi said.
Nonetheless, the results were greeted with enthusiasm by some.
"This is very compelling," said W. Douglas Weaver, M.D., of Henry Ford Hospital & Vascular Institute in Detroit, president of the American College of Cardiology.
Dr. Weaver predicted that the results would soon be rapidly incorporated into ACC-American Heart Association guidelines on heart failure. He said this is the second GISSI trial to demonstrate benefit for omega-3 in cardiovascular disease.
The first trial found that omega-3 reduced the risk of major cardiovascular events following a myocardial infarction.
With the results of two prospective studies in hand, "it raises the level of evidence considerably," said Dr. Weaver. "Our hope is to make [guideline changes on the basis of trial results] almost virtual. The ESC is issuing its new heart failure guidelines this week, but they didn't have these data, so we may be in front of them on these changes since our guidelines committees will be meeting this fall."
But Mariell L. Jessup, M.D., of the University of Pennsylvania, who chairs the committee that is rewriting the ACC-AHA heart failure guidelines, was less enthusiastic. "I don't think we need to tell our elderly patients to take one expensive drug for a minimum benefit."
Nonetheless, she said the news that statins don't work in heart failure had the potential of saving patients money because "they won't need to be spending on statins."
In an interview, Dr. Tavazzi estimated that it would cost about $1.50 a day for patients to buy available over-the-counter omega-3 fatty acid supplements equivalent to a dose of 1 g/day. The study used a prescription omega-3 fatty acid supplement, and he said he could not estimate the cost of daily treatment with the study drug.
The GISSI-HF polyunsaturated fatty acids trial randomized 3,494 patients to polyunsaturated fatty acids (PUFA) and 3,481 to placebo. All patients had New York Heart Association Class IV heart failure.
Seventy-seven percent of the polyunsaturated fatty acids patients were on ACE inhibitors, 19.3% on angiotensin receptor blockers, 65% on beta blockers, 37% on spironolactone, 89.5% on diuretics, 37.1% on digitalis, and 29.4% were on oral anticoagulant medications. Almost half of the patients (47.9%) were taking daily aspirin.
In the control group, 76.9% of the patients were on ACE inhibitors, 18.6% on angiotensin receptor blockers, 64.6% on beta-blockers, 40% on spironolactone, 90% on diuretic drugs, and 37.1% were taking digitalis. As with the PUFA arm, just under half of the sample was taking aspirin.
After a median follow-up of 3.9 years, 955 patients in the PUFA arm died from any cause versus 1,014 deaths in the controls (adjusted HR 0.91, 95% CI 0.833 to 0.993, P=0.04), Dr. Tavazzi said.
There were 1,981 persons hospitalized for cardiovascular reasons in the polyunsaturated fatty acids arm versus 2,053 in the placebo group (HR 0.92, 99% CI 0.849 to 0.999, P=0.009).
In both arms, 3% of patients discontinued therapy, citing gastrointestinal disorders, Dr. Tavazzi said.
Fifty-six patients would need to be treated with polyunsaturated fatty acids (1g/day) for 3.9 years to avoid one death and 44 would need to be treated to avoid the combination endpoint of death or hospitalization.
In the rosuvastatin protocol, researchers randomized 2,285 patients to 10 mg rosuvastatin/day and 2,289 to placebo. The patient demographics were the same as in the GISSI-HF polyunsaturated fatty acids protocol.
Primary endpoints were time to death, and time to death or admission to a hospital for cardiovascular reasons.
Over 3.9 years of follow-up, 657 patients in the rosuvastatin group died form any cause versus 644 in the placebo group.
"In every analysis, every subgroup, treatment with the statin had no effect on outcome," Dr. Tognoni said.
In a commentary that accompanied the studies in The Lancet, Gregg C. Fonarow of UCLA wrote that GISSI-HF results "reinforce the idea that findings in populations without heart failure may or may not extrapolate to patients with heart failure."
The obvious conclusion, Dr. Fonarow wrote, was that for "n-3 fatty acid supplementation, benefits observed in other populations apply to patients with heart failure. For statins, the benefits, unfortunately, seem not to."
The GISSI-HF studies were supported by Societa Prodotti Antibiotici (SPA, Italy), Pfizer, Sigma Tau, and AstraZeneca.
Drs. Tavazzi and Tognoni said they received support from Astra Zeneca. Dr. Fonarow said he received funding from GlaxoSmithKline and Pfizer and consulting or speaker fees from Astra Zeneca, GlaxoSmithKline, Pfizer, Merck, and Schering-Plough.
Dr. Weaver declared grant support from Proctor and Gamble and Schering-Plough and equity or stock interest in Acorn Cardiovascular. Dr. Jessup disclosed support from Medtronic, GlaxoSmithKline, Centracor, and Acorn.
Primary source: European Society of Cardiology meeting/The Lancet
Source reference:
GISSI-HF Investigators "Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): A randomized, double-blind, placebo-controlled trial" Lancet 2008; Published online Aug 31.
Additional source: European Society of Cardiology meeting/The Lancet
Source reference:
GISSI-HF Investigators "Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): A randomized, double-blind, placebo-controlled trial" Lancet 2008; Published online Aug. 31.
Additional source: European Society of Cardiology meeting/The Lancet
Source reference:
Fonarow GC "Statins and n-3 fatty acid supplementation in heart failure" Lancet 2008; Published online Aug. 31.
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