Statins are cholesterol-lowering drugs, highly effective in the primary and secondary prevention of coronary artery disease. It has been found, however, that statins also have nonlipid effects; they can influence different pathways, which have been described to participate in the pathogenesis of acute coronary syndrome (ACS). Inflammation or decreased production of nitric oxide are obvious targets for statin therapy. Recently, several large clinical trials have been published, showing safety and, in some areas, efficacy of administration of statins early after ACS. Furthermore, there is growing evidence from both experimental and small clinical studies that statin therapy may have favourable effects when started as soon as possible after the development of ACS. Confirmation of this approach by large randomized trials is needed; however, based on currently available data, statins have high chance of achieving a similar place in the first-line therapy of ACS as the pillar of contemporary therapeutic strategy, aspirin.

Department of Cardiology Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Zobrazit více v PubMed

Aikawa M, Libby P. The vulnerable atherosclerotic plaque: Pathogenesis and therapeutic approach. Cardiovasc Pathol. 2004;13:125–38. PubMed

Shah PK, Falk E, Badimon JJ, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation. 1995;92:1565–9. PubMed

Loree HM, Kamm RD, Stringfellow RG, Lee RT. Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. Circ Res. 1992;71:850–8. PubMed

Heinecke JW. Oxidized amino acids: Culprits in human atherosclerosis and indicators of oxidative stress. Free Radic Biol Med. 2002;32:1090–101. PubMed

Sugiyama S, Okada Y, Sukhova GK, Virmani R, Heinecke JW, Libby P. Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am J Pathol. 2001;158:879–91. PubMed PMC

Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest. 1996;98:2572–9. PubMed PMC

Libby P. Atherosclerosis: The new view. Sci Am. 2002;286:46–55. PubMed

Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA. 1989;86:2839–43. PubMed PMC

Lupu F, Bergonzelli GE, Heim DA, et al. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries. Arterioscler Thromb. 1993;13:1090–100. PubMed

Dickson BC, Gotlieb AI. Towards understanding acute destabilization of vulnerable atherosclerotic plaques. Cardiovasc Pathol. 2003;12:237–48. PubMed

Libby P. Changing concepts of atherogenesis. J Intern Med. 2000;247:349–58. PubMed

Pinderski LJ, Fischbein MP, Subbanagounder G, et al. Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient mice by altering lymphocyte and macrophage phenotypes. Circ Res. 2002;90:1064–71. PubMed

Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels: The pravastatin inflammation/CRP evaluation (PRINCE): A randomized trial and cohort study. JAMA. 2001;286:64–70. PubMed

Kinlay S, Schwartz GG, Olsson AG, et al. High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study. Circulation. 2003;108:1560–6. PubMed

Ridker PM, Rifai N, Lowenthal SP. Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation. 2001;103:1191–3. PubMed

Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S. Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation. 2001;103:1933–5. PubMed

Riesen WF, Engler H, Risch M, Korte W, Noseda G. Short-term effects of atorvastatin on C-reactive protein. Eur Heart J. 2002;23:794–9. PubMed

van de Ree MA, Huisman MV, Princen HM, Meinders AE, Kluft C. Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus. Atherosclerosis. 2003;166:129–35. PubMed

Koh KK, Schenke WH, Waclawiw MA, Csako G, Cannon RO., 3rd Statin attenuates increase in C-reactive protein during estrogen replacement therapy in postmenopausal women. Circulation. 2002;105:1531–3. PubMed

Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Taylor AJ. Effect of atorvastatin and pravastatin on serum C-reactive protein. Am Heart J. 2003;145:e8. PubMed

Ansell BJ, Watson KE, Weiss RE, Fonarow GC. hsCRP and HDL effects of statins trial (CHEST): Rapid effect of statin therapy on C-reactive protein and high-density lipoprotein levels: A clinical investigation. Heart Dis. 2003;5:2–7. PubMed

Romano M, Diomede L, Sironi M, et al. Inhibition of monocyte chemotactic protein-1 synthesis by statins. Lab Invest. 2000;80:1095–100. PubMed

Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Res. 2001;89:763–71. PubMed

Koh KK, Son JW, Ahn JY, et al. Non-lipid effects of statin on hypercholesterolemic patients established to have coronary artery disease who remained hypercholesterolemic while eating a step-II diet. Coron Artery Dis. 2001;12:305–11. PubMed

Rezaie-Majd A, Maca T, Bucek RA, et al. Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vasc Biol. 2002;22:1194–9. PubMed

Brull DJ, Sanders J, Rumley A, Lowe GD, Humphries SE, Montgomery HE. Statin therapy and the acute inflammatory response after coronary artery bypass grafting. Am J Cardiol. 2001;88:431–3. PubMed

Ikeda U, Shimada K. Statins and monocytes. Lancet. 1999;353:2070. PubMed

Ferro D, Parrotto S, Basili S, Alessandri C, Violi F. Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia. J Am Coll Cardiol. 2000;36:427–31. PubMed

Bustos C, Hernandez-Presa MA, Ortego M, et al. HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol. 1998;32:2057–64. PubMed

Ikeda U, Shimpo M, Ohki R, et al. Fluvastatin inhibits matrix metalloproteinase-1 expression in human vascular endothelial cells. Hypertension. 2000;36:325–9. PubMed

Aikawa M, Rabkin E, Sugiyama S, et al. An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro. Circulation. 2001;103:276–83. PubMed

Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: Implications for plaque stabilization. Circulation. 2001;103:926–33. PubMed

Seljeflot I, Tonstad S, Hjermann I, Arnesen H. Reduced expression of endothelial cell markers after 1 year treatment with simvastatin and atorvastatin in patients with coronary heart disease. Atherosclerosis. 2002;162:179–85. PubMed

Sardo MA, Castaldo M, Cinquegrani M, et al. Effects of atorvastatin treatment on sICAM-1 and plasma nitric oxide levels in hypercholesterolemic subjects. Clin Appl Thromb Hemost. 2002;8:257–63. PubMed

Niwa S, Totsuka T, Hayashi S. Inhibitory effect of fluvastatin, an HMG-CoA reductase inhibitor, on the expression of adhesion molecules on human monocyte cell line. Int J Immunopharmacol. 1996;18:669–75. PubMed

Colli S, Eligini S, Lalli M, Camera M, Paoletti R, Tremoli E. Vastatins inhibit tissue factor in cultured human macrophages. A novel mechanism of protection against atherothrombosis. Arterioscler Thromb Vasc Biol. 1997;17:265–72. PubMed

Ferro D, Basili S, Alessandri C, Cara D, Violi F. Inhibition of tissue-factor-mediated thrombin generation by simvastatin. Atherosclerosis. 2000;149:111–6. PubMed

Nagata K, Ishibashi T, Sakamoto T, et al. Rho/Rho-kinase is involved in the synthesis of tissue factor in human monocytes. Atherosclerosis. 2002;163:39–47. PubMed

Eto M, Kozai T, Cosentino F, Joch H, Luscher TF. Statin prevents tissue factor expression in human endothelial cells: Role of Rho/Rho-kinase and Akt pathways. Circulation. 2002;105:1756–9. PubMed

Camera M, Toschi V, Comparato C, et al. Cholesterol-induced thrombogenicity of the vessel wall: Inhibitory effect of fluvastatin. Thromb Haemost. 2002;87:748–55. PubMed

Baetta R, Camera M, Comparato C, Altana C, Ezekowitz MD, Tremoli E. Fluvastatin reduces tissue factor expression and macrophage accumulation in carotid lesions of cholesterol-fed rabbits in the absence of lipid lowering. Arterioscler Thromb Vasc Biol. 2002;22:692–8. PubMed

Ferro D, Basili S, Alessandri C, Mantovani B, Cordova C, Violi F. Simvastatin reduces monocyte-tissue-factor expression type IIa hypercholesterolaemia. Lancet. 1997;350:1222. PubMed

Holschermann H, Hilgendorff A, Kemkes-Matthes B, et al. Simvastatin attenuates vascular hypercoagulability in cardiac transplant recipients. Transplantation. 2000;69:1830–6. PubMed

Cortellaro M, Cofrancesco E, Arbustini E, et al. Atorvastatin and thrombogenicity of the carotid atherosclerotic plaque: the ATROCAP study. Thromb Haemost. 2002;88:41–7. PubMed

Hansen JB, Huseby KR, Huseby NE, Sandset PM, Hanssen TA, Nordoy A. Effect of cholesterol lowering on intravascular pools of TFPI and its anticoagulant potential in type II hyperlipoproteinemia. Arterioscler Thromb Vasc Biol. 1995;15:879–85. PubMed

Lorena M, Perolini S, Casazza F, Milani M, Cimminiello C. Fluvastatin and tissue factor pathway inhibitor in type IIA and IIB hyperlipidemia and in acute myocardial infarction. Thromb Res. 1997;87:397–403. PubMed

Nordoy A, Bonaa KH, Sandset PM, Hansen JB, Nilsen H. Effect of omega-3 fatty acids and simvastatin on hemostatic risk factors and postprandial hyperlipemia in patients with combined hyperlipemia. Arterioscler Thromb Vasc Biol. 2000;20:259–65. PubMed

Morishita E, Asakura H, Saito M, et al. Elevated plasma levels of free-form of TFPI antigen in hypercholesterolemic patients. Atherosclerosis. 2001;154:203–12. PubMed

Krysiak R, Okopien B, Herman Z. Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes. Drugs. 2003;63:1821–54. PubMed

Szczeklik A, Musial J, Undas A, et al. Inhibition of thrombin generation by simvastatin and lack of additive effects of aspirin in patients with marked hypercholesterolemia. J Am Coll Cardiol. 1999;33:1286–93. PubMed

Musial J, Undas A, Undas R, Brozek J, Szczeklik A. Treatment with simvastatin and low-dose aspirin depresses thrombin generation in patients with coronary heart disease and borderline-high cholesterol levels. Thromb Haemost. 2001;85:221–5. PubMed

Aoki I, Aoki N, Kawano K, et al. Platelet-dependent thrombin generation in patients with hyperlipidemia. J Am Coll Cardiol. 1997;30:91–6. PubMed

Alessandri C, Basili S, Maurelli M, et al. Relationship between prothrombin activation fragment F1+2 and serum cholesterol. Haemostasis. 1996;26:214–9. PubMed

Puccetti L, Bruni F, Di Renzo M, et al. Hypercoagulable state in hypercholesterolemic subjects assessed by platelet-dependent thrombin generation: In vitro effect of cerivastatin. Eur Rev Med Pharmacol Sci. 1999;3:197–204. PubMed

Puccetti L, Bruni F, Bova G, et al. Effect of diet and treatment with statins on platelet-dependent thrombin generation in hypercholesterolemic subjects. Nutr Metab Cardiovasc Dis. 2001;11:378–87. PubMed

Meade TW, Mellows S, Brozovic M, et al. Haemostatic function and ischaemic heart disease: Principal results of the Northwick Park Heart Study. Lancet. 1986;2:533–7. PubMed

Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med. 1984;311:501–5. PubMed

Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA. 1987;258:1183–6. PubMed

Davidson M, McKenney J, Stein E, et al. Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I. Am J Cardiol. 1997;79:1475–81. PubMed

Seeger H, Wallwiener D, Mueck AO. Lipid-independent effects of an estrogen-statin combination: Inhibition of expression of adhesion molecules and plasminogen activator inhibitor-I in human endothelial cell cultures. Climacteric. 2001;4:209–14. PubMed

Warkentin TE. Hemostasis and atherosclerosis. Can J Cardiol. 1995;11(Suppl C):29C–34C. PubMed

Essig M, Nguyen G, Prie D, Escoubet B, Sraer JD, Friedlander G. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase fibrinolytic activity in rat aortic endothelial cells. Role of geranylgeranylation and Rho proteins. Circ Res. 1998;83:683–90. PubMed

Mussoni L, Banfi C, Sironi L, Arpaia M, Tremoli E. Fluvastatin inhibits basal and stimulated plasminogen activator inhibitor 1, but induces tissue type plasminogen activator in cultured human endothelial cells. Thromb Haemost. 2000;84:59–64. PubMed

Haslinger B, Goedde MF, Toet KH, Kooistra T. Simvastatin increases fibrinolytic activity in human peritoneal mesothelial cells independent of cholesterol lowering. Kidney Int. 2002;62:1611–9. PubMed

Morikawa S, Takabe W, Mataki C, et al. The effect of statins on mRNA levels of genes related to inflammation, coagulation, and vascular constriction in HUVEC. Human umbilical vein endothelial cells. J Atheroscler Thromb. 2002;9:178–83. PubMed

Lopez S, Peiretti F, Bonardo B, Juhan-Vague I, Nalbone G. Effect of atorvastatin and fluvastatin on the expression of plasminogen activator inhibitor type-1 in cultured human endothelial cells. Atherosclerosis. 2000;152:359–66. PubMed

Bourcier T, Libby P. HMG CoA reductase inhibitors reduce plasminogen activator inhibitor-1 expression by human vascular smooth muscle and endothelial cells. Arterioscler Thromb Vasc Biol. 2000;20:556–62. PubMed

Ishibashi T, Nagata K, Ohkawara H, et al. Inhibition of Rho/Rho-kinase signaling downregulates plasminogen activator inhibitor-1 synthesis in cultured human monocytes. Biochim Biophys Acta. 2002;1590:123–30. PubMed

Wiesbauer F, Kaun C, Zorn G, Maurer G, Huber K, Wojta J. HMG CoA reductase inhibitors affect the fibrinolytic system of human vascular cells in vitro: A comparative study using different statins. Br J Pharmacol. 2002;135:284–92. PubMed PMC

Tsiara S, Elisaf M, Mikhailidis DP. Early vascular benefits of statin therapy. Curr Med Res Opin. 2003;19:540–56. PubMed

Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet. 1996;348:1079–82. PubMed

Jeremy JY, Rowe D, Emsley AM, Newby AC. Nitric oxide and the proliferation of vascular smooth muscle cells. Cardiovasc Res. 1999;43:580–94. PubMed

De Caterina R, Libby P, Peng HB, et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest. 1995;96:60–8. PubMed PMC

Kalinowski L, Dobrucki IT, Malinski T. Cerivastatin potentiates nitric oxide release and enos expression through inhibition of isoprenoids synthesis. J Physiol Pharmacol. 2002;53:585–95. PubMed

Kalinowski L, Dobrucki LW, Brovkovych V, Malinski T. Increased nitric oxide bioavailability in endothelial cells contributes to the pleiotropic effect of cerivastatin. Circulation. 2002;105:933–8. 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

Laufs U, Gertz K, Dirnagl U, Bohm M, Nickenig G, Endres M. Rosuvastatin, a new HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice. Brain Res. 2002;942:23–30. PubMed

Laufs U, Endres M, Custodis F, et al. Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation. 2000;102:3104–10. PubMed

Laufs U, Liao JK. Targeting Rho in cardiovascular disease. Circ Res. 2000;87:526–8. PubMed

Jagroop IA, Mikhailidis DP. Effect of endothelin-1 on human platelet shape change: reversal of activation by naftidrofuryl. Platelets. 2000;11:272–7. PubMed

Barton M, Lattmann T, d’Uscio LV, Luscher TF, Shaw S. Inverse regulation of endothelin-1 and nitric oxide metabolites in tissue with aging: implications for the age-dependent increase of cardiorenal disease. J Cardiovasc Pharmacol. 2000;36(Suppl 1):S153–6. PubMed

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;101:2711–9. PubMed PMC

Dupuis J, Tardif JC, Cernacek P, Theroux P. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial. Circulation. 1999;99:3227–33. PubMed

de Jongh S, Lilien MR, op’t Roodt J, Stroes ES, Bakker HD, Kastelein JJ. Early statin therapy restores endothelial function in children with familial hypercholesterolemia. J Am Coll Cardiol. 2002;40:2117–21. PubMed

Marchesi S, Lupattelli G, Siepi D, et al. Short-term atorvastatin treatment improves endothelial function in hypercholesterolemic women. J Cardiovasc Pharmacol. 2000;36:617–21. PubMed

Tsunekawa T, Hayashi T, Kano H, et al. Cerivastatin, a hydroxymethylglutaryl coenzyme a reductase inhibitor, improves endothelial function in elderly diabetic patients within 3 days. Circulation. 2001;104:376–9. PubMed

Omori H, Nagashima H, Tsurumi Y, et al. Direct in vivo evidence of a vascular statin: A single dose of cerivastatin rapidly increases vascular endothelial responsiveness in healthy normocholesterolaemic subjects. Br J Clin Pharmacol. 2002;54:395–9. PubMed PMC

Suzumura K, Yasuhara M, Narita H. Superoxide anion scavenging properties of fluvastatin and its metabolites. Chem Pharm Bull (Tokyo) 1999;47:1477–80. PubMed

Suzumura K, Yasuhara M, Tanaka K, Odawara A, Narita H, Suzuki T. An in vitro study of the hydroxyl radical scavenging property of fluvastatin, and HMG-CoA reductase inhibitor. Chem Pharm Bull (Tokyo) 1999;47:1010–2. PubMed

Suzumura K, Yasuhara M, Tanaka K, Suzuki T. Protective effect of fluvastatin sodium (XU-62-320), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on oxidative modification of human low-density lipoprotein in vitro. Biochem Pharmacol. 1999;57:697–703. PubMed

Hussein O, Schlezinger S, Rosenblat M, Keidar S, Aviram M. Reduced susceptibility of low density lipoprotein (LDL) to lipid peroxidation after fluvastatin therapy is associated with the hypocholesterolemic effect of the drug and its binding to the LDL. Atherosclerosis. 1997;128:11–8. PubMed

Fuhrman B, Koren L, Volkova N, Keidar S, Hayek T, Aviram M. Atorvastatin therapy in hypercholesterolemic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Atherosclerosis. 2002;164:179–85. PubMed

Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet. 1994;344:1383–9. PubMed

Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001–9. PubMed

Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339:1349–57. PubMed

Stenestrand U, Wallentin L. Early statin treatment following acute myocardial infarction and 1-year survival. JAMA. 2001;285:430–6. PubMed

Aronow HD, Topol EJ, Roe MT, et al. Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: An observational study. Lancet. 2001;357:1063–8. PubMed

Cannon CP, McCabe CH, Bentley J, Braunwald E. Early statin therapy is associated with markedly lower mortality in patients with acute coronary syndromes: observations from OPUS-TIMI 16 [abstract] J Am Coll Cardiol. 2001;37(Suppl A):334A. (Abst) PubMed

Newby LK, Kristinsson A, Bhapkar MV, et al. Early statin initiation and outcomes in patients with acute coronary syndromes. JAMA. 2002;287:3087–95. PubMed

Heeschen C, Hamm CW, Laufs U, Snapinn S, Bohm M, White HD. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation. 2002;105:1446–52. PubMed

Schiele R, Gitt AK, Heer T. Early statin use in acute myocardial is associated with a reduced hospital mortality: Results of the Mitra-2 [abstract] Circulation. 2000;102(Suppl 2):II-435. (Abst)

Briguori C, Colombo A, Airoldi F, et al. Statin administration before percutaneous coronary intervention: Impact on periprocedural myocardial infarction. Eur Heart J. 2004;25:1822–8. PubMed

Kayikcioglu M, Turkoglu C, Kultursay H, Evrengul H, Can L. The short term results of combined use of pravastatin with thrombolytic therapy in acute myocardial infarction. Circulation. 1999;100(Suppl 1):I-303. (Abst)

Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial. JAMA. 2001;285:1711–8. PubMed

Liem AH, van Boven AJ, Veeger NJ, et al. Effect of fluvastatin on ischaemia following acute myocardial infarction: A randomized trial. Eur Heart J. 2002;23:1931–7. PubMed

Arntz HR, Agrawal R, Wunderlich W, et al. Beneficial effects of pravastatin (+/−colestyramine/niacin) initiated immediately after a coronary event (the randomized Lipid-Coronary Artery Disease [L-CAD] Study) Am J Cardiol. 2000;86:1293–8. PubMed

Serruys PW, de Feyter P, Macaya C, et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: A randomized controlled trial. JAMA. 2002;287:3215–22. PubMed

Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504. PubMed

Thompson PL, Meredith I, Amerena J, Campbell TJ, Sloman JG, Harris PJ. Effect of pravastatin compared with placebo initiated within 24 hours of onset of acute myocardial infarction or unstable angina: The Pravastatin in Acute Coronary Treatment (PACT) trial. Am Heart J. 2004;148:e2. PubMed

de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: Phase Z of the A to Z trial. JAMA. 2004;292:1307–16. PubMed

LaBlanche JM, Jukema JW, Charbonneau F, et al. ESC Congress; 2004. Munich: 2004. PRINCESS: Prevention of ischemic events by early treatment of cerivastatin after acute myocardial infarction.

Lefer AM, Campbell B, Shin YK, Scalia R, Hayward R, Lefer DJ. Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts. Circulation. 1999;100:178–84. PubMed

Ueda Y, Kitakaze M, Komamura K, et al. Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction. J Am Coll Cardiol. 1999;34:2120–5. PubMed

Lefer DJ, Scalia R, Jones SP, et al. HMG-CoA reductase inhibition protects the diabetic myocardium from ischemia-reperfusion injury. FASEB J. 2001;15:1454–6. PubMed

Di Napoli P, Antonio Taccardi A, Grilli A, et al. Simvastatin reduces reperfusion injury by modulating nitric oxide synthase expression: An ex vivo study in isolated working rat hearts. Cardiovasc Res. 2001;51:283–93. PubMed

Bauersachs J, Galuppo P, Fraccarollo D, Christ M, Ertl G. Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme a reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction. Circulation. 2001;104:982–5. PubMed

Hayashidani S, Tsutsui H, Shiomi T, et al. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation. 2002;105:868–73. PubMed

Bell RM, Yellon DM. Atorvastatin, administered at the onset of reperfusion, and independent of lipid lowering, protects the myocardium by up-regulating a pro-survival pathway. J Am Coll Cardiol. 2003;41:508–15. PubMed

Wolfrum S, Dendorfer A, Schutt M, et al. Simvastatin acutely reduces myocardial reperfusion injury in vivo by activating the phosphatidylinositide 3-kinase/Akt pathway. J Cardiovasc Pharmacol. 2004;44:348–55. PubMed

Ostadal P, Alan D, Hajek P, et al. The effect of early treatment by cerivastatin on the serum level of C-reactive protein, interleukin-6, and interleukin-8 in the patients with unstable angina and non-Q-wave myocardial infarction. Mol Cell Biochem. 2003;246:45–50. PubMed

Ostadal P, Alan D, Hajek P, et al. Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial) Curr Control Trials Cardiovasc Med. 2005. (In press) PubMed PMC

Statins as first-line therapy for acute coronary syndrome?

Immediate effect of fluvastatin on lipid levels in acute coronary syndrome