Skip to main content
Erschienen in: Cardiovascular Drugs and Therapy 1/2011

01.02.2011

Statins in Heart Failure—Where Do We Stand?

verfasst von: Kristopher S. Lyons, Gary E. McVeigh, Mark T. Harbinson

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

HMG Co-A reductase inhibitors (statins) are a group of drugs which lower cholesterol by inhibiting the conversion of HMG Co-A to mevalonate early in the cholesterol synthetic pathway. They are used in the primary and secondary prevention of cardiovascular events in patients deemed to be at increased risk and their benefit in patients with ischaemic heart disease is well supported. Their use in patients with heart failure (HF) however, is controversial. Evidence from observational and mechanistic studies suggests that statins should benefit patients with HF. However, larger randomised controlled trials have failed to demonstrate these expected benefits. The aim of this review article is to summarise the data from trials of statin use in patients with HF and attempt to explain the apparent conflict between recent placebo controlled trials and earlier observational and mechanistic studies.
Literatur
1.
Zurück zum Zitat Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–9. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–9.
2.
Zurück zum Zitat Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial. Lancet. 2002;360:7–22.CrossRef Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial. Lancet. 2002;360:7–22.CrossRef
3.
Zurück zum Zitat Pedersen TR, Faergeman O, Kastelein JJP, et al. High dose atorvastatin vrs usual dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294:2437–45.PubMedCrossRef Pedersen TR, Faergeman O, Kastelein JJP, et al. High dose atorvastatin vrs usual dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294:2437–45.PubMedCrossRef
4.
Zurück zum Zitat Foody JM, Shah R, Galusha D, et al. Statins and mortality among elderly patients hospitalized with heart failure. Circulation. 2006;113:1086–92.PubMedCrossRef Foody JM, Shah R, Galusha D, et al. Statins and mortality among elderly patients hospitalized with heart failure. Circulation. 2006;113:1086–92.PubMedCrossRef
5.
Zurück zum Zitat Go AS, Lee WY, Yang J, et al. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA. 2006;296:2105–11.PubMedCrossRef Go AS, Lee WY, Yang J, et al. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA. 2006;296:2105–11.PubMedCrossRef
6.
Zurück zum Zitat Horwich T, MacLellan W, Fonarow G. Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure. J Am Coll Cardiol. 2004;43:642–8.PubMedCrossRef Horwich T, MacLellan W, Fonarow G. Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure. J Am Coll Cardiol. 2004;43:642–8.PubMedCrossRef
7.
Zurück zum Zitat Segal R, Pitt B, Pode-Wilson P, on behalf of the ELITE II, et al. Effects of HMG-COA reductase inhibitors (statins) in patients with heart failure [abstract]. Eur J Heart Fail. 2000;2:96.CrossRef Segal R, Pitt B, Pode-Wilson P, on behalf of the ELITE II, et al. Effects of HMG-COA reductase inhibitors (statins) in patients with heart failure [abstract]. Eur J Heart Fail. 2000;2:96.CrossRef
8.
Zurück zum Zitat Perreault S, Dragomir A, Blais L, et al. Impact of adherence to statins on chronic heart failure in primary prevention. Brit J Clin Pharmacol. 2008;66:706–16. Perreault S, Dragomir A, Blais L, et al. Impact of adherence to statins on chronic heart failure in primary prevention. Brit J Clin Pharmacol. 2008;66:706–16.
9.
Zurück zum Zitat Kjekshus J, Pedersen TR, Olsson AG, et al. The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail. 1997;3:249–54.PubMedCrossRef Kjekshus J, Pedersen TR, Olsson AG, et al. The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail. 1997;3:249–54.PubMedCrossRef
10.
Zurück zum Zitat Strey CH, Young JH, Lainchbury JH, et al. Short term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non-ischaemic heart failure. Heart. 2006;92:1603–9.PubMedCrossRef Strey CH, Young JH, Lainchbury JH, et al. Short term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non-ischaemic heart failure. Heart. 2006;92:1603–9.PubMedCrossRef
11.
Zurück zum Zitat Verma S, Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation. 2002;105:546–9.PubMedCrossRef Verma S, Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation. 2002;105:546–9.PubMedCrossRef
12.
Zurück zum Zitat Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129–35.PubMed Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129–35.PubMed
13.
Zurück zum Zitat Bucci M, Gratton JP, Rudic RD, et al. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat Med. 2000;6:1362–7.PubMedCrossRef Bucci M, Gratton JP, Rudic RD, et al. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat Med. 2000;6:1362–7.PubMedCrossRef
14.
Zurück zum Zitat Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest. 1998;101:2711–271.PubMedCrossRef Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest. 1998;101:2711–271.PubMedCrossRef
15.
Zurück zum Zitat Hamilton PK, Hughes SMT, Plumb RD, et al. Statins have beneficial effects on platelet free radical activity and intracellular distribution of GTPases in hyperlipidaemia. Clin Sci. 2010;118:359–66.PubMedCrossRef Hamilton PK, Hughes SMT, Plumb RD, et al. Statins have beneficial effects on platelet free radical activity and intracellular distribution of GTPases in hyperlipidaemia. Clin Sci. 2010;118:359–66.PubMedCrossRef
16.
Zurück zum Zitat Landmesser U, Bahlmann F, Mueller M, et al. Simvastatin versus Ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation. 2005;111:2356–63.PubMedCrossRef Landmesser U, Bahlmann F, Mueller M, et al. Simvastatin versus Ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation. 2005;111:2356–63.PubMedCrossRef
17.
Zurück zum Zitat Landmesser U, Engberding N, Bahlmann FH, et al. Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation. 2004;110:1933–9.PubMedCrossRef Landmesser U, Engberding N, Bahlmann FH, et al. Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation. 2004;110:1933–9.PubMedCrossRef
18.
Zurück zum Zitat Yin W, Chen J, Jen H, et al. Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure. Am Heart J. 2004;147:931–8.PubMedCrossRef Yin W, Chen J, Jen H, et al. Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure. Am Heart J. 2004;147:931–8.PubMedCrossRef
19.
Zurück zum Zitat Sola S, Mir MQS, Lerakis S, et al. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. JACC. 2006;47:332–7.PubMed Sola S, Mir MQS, Lerakis S, et al. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. JACC. 2006;47:332–7.PubMed
20.
Zurück zum Zitat Node K, Fujita M, Kitakaze M, et al. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation. 2003;108:839–43.PubMedCrossRef Node K, Fujita M, Kitakaze M, et al. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation. 2003;108:839–43.PubMedCrossRef
21.
Zurück zum Zitat The Corona Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357:2248–61.CrossRef The Corona Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357:2248–61.CrossRef
22.
Zurück zum Zitat 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;372:1231–9.CrossRef 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;372:1231–9.CrossRef
23.
Zurück zum Zitat Lipinski MJ, Cauthen CA, Biondi-Zoccai GGL, et al. Meta-analysis of randomized controlled trials of statins vrs placebo in patients with heart failure. Am J Cardiol. 2009;104:1708–16.PubMedCrossRef Lipinski MJ, Cauthen CA, Biondi-Zoccai GGL, et al. Meta-analysis of randomized controlled trials of statins vrs placebo in patients with heart failure. Am J Cardiol. 2009;104:1708–16.PubMedCrossRef
24.
25.
Zurück zum Zitat Laufs U, Custodis F, Bohm M. Who does not need a statin? Too late in end-stage renal disease and heart failure? Heart. 2008;94:1138–40.PubMed Laufs U, Custodis F, Bohm M. Who does not need a statin? Too late in end-stage renal disease and heart failure? Heart. 2008;94:1138–40.PubMed
26.
Zurück zum Zitat Cleland JGF, McMurray JJV, Kjekshus J, on behalf of the CORONA Study Group, et al. Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). J Am Coll Cardiol. 2009;54:1850–9.PubMedCrossRef Cleland JGF, McMurray JJV, Kjekshus J, on behalf of the CORONA Study Group, et al. Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). J Am Coll Cardiol. 2009;54:1850–9.PubMedCrossRef
27.
Zurück zum Zitat Vredevoe DL, Woo MA, Doering LV, et al. Skin test anergy in advanced heart failure secondary to either ischaemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1998;82:323–8.PubMedCrossRef Vredevoe DL, Woo MA, Doering LV, et al. Skin test anergy in advanced heart failure secondary to either ischaemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1998;82:323–8.PubMedCrossRef
28.
Zurück zum Zitat Horwich TB, Hamilton MA, MacLellan WR, et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail. 2002;8:216–24.PubMedCrossRef Horwich TB, Hamilton MA, MacLellan WR, et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail. 2002;8:216–24.PubMedCrossRef
29.
Zurück zum Zitat Rauchhaus M, Clark A, Doehner W, et al. The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol. 2003;42:1933–40.PubMedCrossRef Rauchhaus M, Clark A, Doehner W, et al. The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol. 2003;42:1933–40.PubMedCrossRef
30.
31.
Zurück zum Zitat Kucharská J, Gvozdjáková A, Šimko F. Simvastatin decreased CoQ in the left ventricle and skeletal muscle, but not in the brain and liver in L-NAME-induced hypertension. Physio Res. 2007;56:S49–54. Kucharská J, Gvozdjáková A, Šimko F. Simvastatin decreased CoQ in the left ventricle and skeletal muscle, but not in the brain and liver in L-NAME-induced hypertension. Physio Res. 2007;56:S49–54.
32.
Zurück zum Zitat Mabuchi H, Higashikata T, Kawashiri M, et al. Reduction of serum Ubiquinol-10 levels by atoravastatin in hypercholesterolaemic patients. J Atheroscler Thromb. 2005;12:111–9.PubMed Mabuchi H, Higashikata T, Kawashiri M, et al. Reduction of serum Ubiquinol-10 levels by atoravastatin in hypercholesterolaemic patients. J Atheroscler Thromb. 2005;12:111–9.PubMed
33.
Zurück zum Zitat Molyneux SL, Florkowski CM, George PM, et al. Coenzyme Q10: an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol. 2008;52:1435–41.PubMedCrossRef Molyneux SL, Florkowski CM, George PM, et al. Coenzyme Q10: an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol. 2008;52:1435–41.PubMedCrossRef
34.
Zurück zum Zitat Florkowski CM, Molyneux SL, George PM. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2008;358:1301.PubMedCrossRef Florkowski CM, Molyneux SL, George PM. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2008;358:1301.PubMedCrossRef
35.
Zurück zum Zitat McMurray JJV, Dunselman P, Wedel H, et al. Coenzyme Q10, rosuvastatin and clinical outcomes in heart failure. J Am Coll Cardiol. 2010;56:1196–204.PubMedCrossRef McMurray JJV, Dunselman P, Wedel H, et al. Coenzyme Q10, rosuvastatin and clinical outcomes in heart failure. J Am Coll Cardiol. 2010;56:1196–204.PubMedCrossRef
36.
Zurück zum Zitat Keith M, Mazer CD, Mikhail P, et al. Co-enzyme Q10 in patients undergoing CABG: effect of statins and nutritional supplementation. Nutr Metab Cardiovasc Dis. 2008;18:105–11.PubMedCrossRef Keith M, Mazer CD, Mikhail P, et al. Co-enzyme Q10 in patients undergoing CABG: effect of statins and nutritional supplementation. Nutr Metab Cardiovasc Dis. 2008;18:105–11.PubMedCrossRef
37.
Zurück zum Zitat Kuettner A, Pieper A, Koch J, et al. Influence of coenzyme Q10 and cerivastatin on the flow-mediated vasodilation of the brachial artery: results of the ENDOTACT study. Int J Cardiol. 2005;98:413–9.PubMedCrossRef Kuettner A, Pieper A, Koch J, et al. Influence of coenzyme Q10 and cerivastatin on the flow-mediated vasodilation of the brachial artery: results of the ENDOTACT study. Int J Cardiol. 2005;98:413–9.PubMedCrossRef
38.
Zurück zum Zitat Sander S, Coleman CI, Patel AA, et al. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail. 2006;12:464–72.PubMedCrossRef Sander S, Coleman CI, Patel AA, et al. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail. 2006;12:464–72.PubMedCrossRef
39.
Zurück zum Zitat Shin MJ, Chung N, Lee JH, et al. Effect of simvastatin on plasma antioxidant status and vitamins in hypercholesterolaemic patients. Int J Cardiol. 2007;118:173–7.PubMedCrossRef Shin MJ, Chung N, Lee JH, et al. Effect of simvastatin on plasma antioxidant status and vitamins in hypercholesterolaemic patients. Int J Cardiol. 2007;118:173–7.PubMedCrossRef
40.
Zurück zum Zitat Mortensen SA. Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of “Q-symbio”—A multinational trial. Biofactors. 2003;18:79–89.PubMedCrossRef Mortensen SA. Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of “Q-symbio”—A multinational trial. Biofactors. 2003;18:79–89.PubMedCrossRef
41.
Zurück zum Zitat Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR trial). Am J Cardiol. 2003;92:152–60.PubMedCrossRef Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR trial). Am J Cardiol. 2003;92:152–60.PubMedCrossRef
42.
Zurück zum Zitat Susic D, Varagic J, Ahn J, et al. Beneficial pleiotropic vascular effects of rosuvastatin in two hypertensive models. J Am Coll Cardiol. 2003;42:1091–7.PubMedCrossRef Susic D, Varagic J, Ahn J, et al. Beneficial pleiotropic vascular effects of rosuvastatin in two hypertensive models. J Am Coll Cardiol. 2003;42:1091–7.PubMedCrossRef
43.
Zurück zum Zitat Stalker TJ, Lefer AM, Scalia R. A new HMG-CoA reductase inhibitor, rosuvastatin, exerts anti-inflammatory effects on the microvascular endothelium: the role of mevalonic acid. Br J Pharm. 2001;133:406–12.CrossRef Stalker TJ, Lefer AM, Scalia R. A new HMG-CoA reductase inhibitor, rosuvastatin, exerts anti-inflammatory effects on the microvascular endothelium: the role of mevalonic acid. Br J Pharm. 2001;133:406–12.CrossRef
44.
Zurück zum Zitat The Jupiter study group. Rosuvastatin to prevent vascular events in men and women with elevated CRP. N Engl J Med. 2008;359:2195–207.CrossRef The Jupiter study group. Rosuvastatin to prevent vascular events in men and women with elevated CRP. N Engl J Med. 2008;359:2195–207.CrossRef
45.
Zurück zum Zitat ESC taskforce. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Health J. 2008;29:2388–442. ESC taskforce. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Health J. 2008;29:2388–442.
46.
Zurück zum Zitat NICE Guideline Chronic Heart Failure. Management of chronic heart failure in adults in primary and secondary care. July 2003. NICE Guideline Chronic Heart Failure. Management of chronic heart failure in adults in primary and secondary care. July 2003.
47.
Zurück zum Zitat Silver MA, Langsjoen PH, Szabo S, et al. Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction. Am J Cardiol. 2004;94:1306–10.PubMedCrossRef Silver MA, Langsjoen PH, Szabo S, et al. Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction. Am J Cardiol. 2004;94:1306–10.PubMedCrossRef
Metadaten
Titel
Statins in Heart Failure—Where Do We Stand?
verfasst von
Kristopher S. Lyons
Gary E. McVeigh
Mark T. Harbinson
Publikationsdatum
01.02.2011
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 1/2011
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-010-6269-1

Weitere Artikel der Ausgabe 1/2011

Cardiovascular Drugs and Therapy 1/2011 Zur Ausgabe

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.