Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n‐3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure

Tavazzi, Luigi; Tognoni, Gianni; Franzosi, Maria Grazia; Latini, Roberto; Maggioni, Aldo P.; Marchioli, Roberto; Nicolosi, Gian Luigi; Porcu, Maurizio

doi:10.1016/j.ejheart.2004.03.001

Cited by 216 publications

(113 citation statements)

References 53 publications

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“…In this context, it is worth noting that 2 large prospective studies (the Gruppo Italiano per lo Studio della Soprawivenza nell'Infarto Miocardico-Heart Failure trial [GISSI-HF] and the Controlled Rosuvastatin Multinational Trial in HF [CORONA]) were designed to investigate the impact of rosuvastatin on the mortality and morbidity in patients with symptomatic HF. 22,23 In conclusion, our findings show that atorvastatin treatment is associated with better cardiac function parameters in HF, and suggest that this drug may represent an advantageous additional treatment option for patients with HF, irrespective of underlying etiology.…”

Section: Resultsmentioning

confidence: 55%

Atorvastatin Therapy Is Associated with Reduced Levels of N‐terminal Prohormone Brain Natriuretic Peptide and Improved Cardiac Function in Patients with Heart Failure

Stypmann

Schubert²,

Welp³

et al. 2008

Clinical Cardiology

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BackgroundStatins have been suggested to improve cardiac function, but the evidence underlying beneficial effects of statins in heart failure (HF) is insufficient. We analyzed plasma N‐terminal prohormone brain natriuretic peptide (NT‐proBNP) levels and cardiac function in patients with HF of various etiologies, and who were treated with or without statins.HypothesisStatin treatment is associated with improved cardiac function in HF.MethodsThe study cohort consisted of 139 consecutive male patients receiving atorvastatin (n = 44), simvastatin (n = 29), pravastatin (n = 19), or no statin (n = 47). The NT‐proBNP levels were measured using electroluminescence immunoassay. Left ventricular end‐diastolic diameter (LVEDD), fractional shortening (FS), and ejection fraction (EF) were determined by echocardiography.ResultsPatients receiving atorvastatin presented with reduced NT‐proBNP levels (1,552 ± 3,416 versus 3,771 ± 6,763 pg/mL; p < 0.01), and improved values of LVEDD (65.2 ± 8.9 versus 70.7 ± 10.9 mm; p < 0.05) and EF (33.2 ± 12.6 versus 28.2 ± 9.6%; p < 0.05). By contrast, plasma NT‐proBNP and cardiac parameters in patients treated with statins other than atorvastatin did not significantly differ from control. Atorvastatin treatment was equally effective in patients with ischemic and nonischemic HF.ConclusionsAtorvastatin treatment is associated with improved cardiac function in HF, and may represent an additional option for patients with this disease. Copyright © 2008 Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 55%

Atorvastatin Therapy Is Associated with Reduced Levels of N‐terminal Prohormone Brain Natriuretic Peptide and Improved Cardiac Function in Patients with Heart Failure

Stypmann

Schubert²,

Welp³

et al. 2008

Clinical Cardiology

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“…Thus, the improvements in heart function by statins might be owing to cholesterol-independent mechanisms. Currently, there are two large ongoing prospective trials, CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure) and GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico -Insufficienza Cardiaca), which will help to determine whether statin therapy is effective in patients with ischemic and non-ischemic heart failure [26,27].…”

Section: Clinical Trials With Statinsmentioning

confidence: 99%

Pleiotropic effects of statin therapy: molecular mechanisms and clinical results

Wang

Liu

Liao

2008

Trends in Molecular Medicine

537

394

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Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is required for cholesterol biosynthesis, and are beneficial in the primary and secondary prevention of cardiovascular disease. Most of the benefits of statin therapy are owing to the lowering of serum cholesterol levels. However, by inhibiting HMG-CoA reductase, statins can also inhibit the synthesis of isoprenoids, which are important lipid attachments for intracellular signaling molecules, such as Rho, Rac and Cdc42. Therefore, it is possible that statins might exert cholesterol-independent or 'pleiotropic' effects through direct inhibition of these small GTP-binding proteins. Recent studies have shown that statins might have important roles in diseases that are not mediated by cholesterol. Here, we review data from recent clinical trials that support the concept of statin pleiotropy and provide a rationale for their clinical importance. [6], have demonstrated the beneficial effects of statin therapy for primary and secondary prevention of cardiovascular disease. Because 60-70% of serum cholesterol is derived from hepatic synthesis and HMG-CoA reductase is the crucial, rate-limiting enzyme in the cholesterol biosynthetic pathway, inhibition of this enzyme by statins results in a dramatic reduction in circulating low-density lipoprotein (LDL)-cholesterol (Figure 1). In addition, reduction of LDL-cholesterol leads to upregulation of the LDL receptor and increased LDL clearance. The lowering of serum cholesterol levels is therefore thought to be the primary mechanism underlying the therapeutic benefits of statin therapy in cardiovascular disease [1]. Pleiotropy of statins: beyond cholesterol loweringStatins, however, might also exert cholesterol-independent or pleiotropic effects. By inhibiting the conversion of HMG-CoA to L-mevalonic acid, statins prevent the synthesis of important isoprenoids, such as farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP), which are precursors of cholesterol biosynthesis [7] (Figure 1). These intermediates serve as important lipid attachments for the post-translational modification of proteins, such as nuclear lamins, Ras, Rho, Rac and Rap [8]. These isoprenylated proteins constitute approximately 2% of total cellular proteins [9]. Protein isoprenylation (see Glossary) enables proper subcellular localization and trafficking of intracellular proteins. Given that isoprenylated proteins might

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“…Over a median follow-up of 33 months there were no significant differences in the primary end point or in all-cause mortality, the rate of coronary events, the effects on New York Heart Association class or the rate of newly diagnosed diabetes. Other large clinical trials (GISSI-HF) 128 are also under way to further clarify the effects of statin treatment in heart failure.…”

Section: Chaptermentioning

confidence: 99%

Early high-dose lipid-lowering therapy to avoid cardiac events: a systematic review and economic evaluation

Ara

Pandor²,

Stevens³

et al. 2009

Health Technol Assess

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How to obtain copies of this and other HTA programme reports An electronic version of this publication, in Adobe Acrobat format, is available for downloading free of charge for personal use from the HTA website (www.hta.ac.uk). A fully searchable CD-ROM is also available (see below).Printed copies of HTA monographs cost £20 each (post and packing free in the UK) to both public and private sector purchasers from our Despatch Agents.Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per monograph and for the rest of the world £3 per monograph.You can order HTA monographs from our Despatch Agents:-fax (with credit card or official purchase order) -post (with credit card or official purchase order or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you either to pay securely by credit card or to print out your order and then post or fax it. Contact details are as follows: Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltd and drawn on a bank with a UK address. Paying by credit cardThe following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard, Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain email.Paying by official purchase order You can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK. We cannot at present accept purchase orders from commercial companies or from outside the UK. How do I get a copy of HTA on CD?Please use the form on the HTA website (www.hta.ac.uk/htacd.htm). Or contact Direct Mail Works (see contact details above) by email, post, fax or phone. HTA on CD is currently free of charge worldwide.The website also provides information about the HTA programme and lists the membership of the various committees. HTA NIHR Health Technology Assessment programmeT he Health Technology Assessment (HTA) programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care. The research findings from the HTA programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the 'National Knowledge Service'. The HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projects. First is the commissioned route. Suggestions for research are actively sought from people working in t...

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Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n‐3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure

Cited by 216 publications

References 53 publications

Atorvastatin Therapy Is Associated with Reduced Levels of N‐terminal Prohormone Brain Natriuretic Peptide and Improved Cardiac Function in Patients with Heart Failure

Atorvastatin Therapy Is Associated with Reduced Levels of N‐terminal Prohormone Brain Natriuretic Peptide and Improved Cardiac Function in Patients with Heart Failure

Pleiotropic effects of statin therapy: molecular mechanisms and clinical results

Early high-dose lipid-lowering therapy to avoid cardiac events: a systematic review and economic evaluation

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