Fast track — ArticlesEffect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial
Introduction
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (known as statins) are among the most successful drugs discovered and incorporated into clinical practice over the past decades for both primary and secondary prevention of atherothrombosis. In addition to their lipid-lowering action, statins have been postulated to have so-called pleiotropic actions,1 including anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects; improvement of endothelial dysfunction; inhibition of neurohormonal activation; and prevention of cardiac arrhythmias.1, 2, 3, 4, 5 Most of these effects can target important components of the complex physiopathology of heart failure.6
Large observational studies,2, 7 several post-hoc analyses of randomised clinical trials testing drugs that differ from statins,8, 9, 10, 11, 12, 13, 14, 15 and small prospective trials16, 17, 18, 19 have suggested that statins could be beneficial to patients with heart failure. Furthermore, two meta-analyses of statin use in observational and randomised clinical trials2, 8 confirmed a reduction in cardiovascular mortality in patients with heart failure of both ischaemic and non-ischaemic cause. However, randomised controlled trials specifically investigating the efficacy and safety of statins in heart failure were needed because of the methodological weaknesses that were inherent in previous studies.
The Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca (GISSI) decided to undertake a study in patients with symptomatic heart failure of any cause and with any level of left ventricular systolic function, to test the hypothesis that the administration of the statin rosuvastatin would be effective and safe.
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Patients
We did a randomised, double-blind, placebo-controlled, multicentre study, involving 326 cardiology and 31 internal medicine centres in Italy (figure 1). The design of the GISSI-HF trial has been described in detail elsewhere, including the randomisation, monitoring, and follow-up procedures.20
Eligible patients were men and women aged 18 years or older, with symptomatic heart failure that was classified as New York Heart Association (NYHA) functional class II–IV, who were being treated according
Results
4631 patients were randomly assigned (figure 1). We disqualified information from 57 patients at one site after randomisation, before unblinding, because the adequacy of the informed consent process and quality of data could not be ensured. Of the remaining 4574 patients, 2285 were assigned to receive rosuvastatin and 2289 to receive placebo. Follow-up ended on March 31, 2008. The median duration of follow-up was 3·9 years (IQR 3·0–4·4).
Table 1 shows the baseline characteristics of all
Discussion
This trial aimed to investigate the efficacy and safety of rosuvastatin at the usual start dose (10 mg daily) in a broad population of symptomatic patients with heart failure, irrespective of age, ischaemic and non-ischaemic cause, and LVEF. We consistently noted no effect on primary and secondary endpoints, and on all planned subgroup analyses.
Almost uniformly, several observational studies undertaken in different experimental and clinical conditions, and post-hoc analyses of randomised
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