Articles1 June 2004
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    Background:

    Statins administered early in patients with acute coronary syndromes may lead to modest reductions in recurrent ischemic events.

    Objective:

    To examine the association between previous and early in-hospital statin therapy and the presentation and outcomes of an acute coronary syndrome.

    Design:

    Cohort study.

    Setting:

    94 hospitals in 14 countries participating in the Global Registry of Acute Coronary Events (GRACE).

    Patients:

    19 537 patients with an acute coronary syndrome who were enrolled from April 1999 to September 2002.

    Measurements:

    Statin use before and after presentation with an acute coronary syndrome and associated rates of myocardial infarction, hospital complications, and hospital mortality. The composite end point included death, in-hospital myocardial infarction, and stroke.

    Results:

    Patients who were already taking statins when they presented to the hospital were less likely to have ST-segment elevation (odds ratio [OR], 0.79 [95% CI, 0.71 to 0.88]) or myocardial infarction (OR, 0.78 [CI, 0.70 to 0.86]). Patients who continued to take statins in the hospital were less likely to experience complications or die than patients who never received statins (OR, 0.66 [CI, 0.56 to 0.77]). Patients not previously taking statins who began statin therapy in the hospital were less likely to die than patients who never received statin therapy (OR, 0.38 [CI, 0.30 to 0.48]). However, adjustment for the hospital of admission attenuated the association between initiation of statin therapy and the composite end point (OR, 0.84 [CI, 0.65 to 1.10]).

    Limitations:

    This observational study cannot exclude confounding by clinical and hospital factors.

    Conclusions:

    These data support the hypothesis that statin therapy can modulate early pathophysiologic processes in patients with acute coronary syndromes. A randomized trial of statin therapy in acute myocardial infarction is warranted.

    *For a list of the members of the GRACE Scientific Advisory Committee, see the Appendix.

    References

    • 1. Sacks FMPfeffer MAMoye LARouleau JLRutherford JDCole TGet 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 Med1996;335:1001-9. [PMID: 8801446] CrossrefMedlineGoogle Scholar
    • 2. 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 Med1998;339:1349-57. [PMID: 9841303] CrossrefMedlineGoogle Scholar
    • 3. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet1994;344:1383-9. [PMID: 7968073] MedlineGoogle Scholar
    • 4. Rosenson RSTangney CCAntiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA1998;279:1643-50. [PMID: 9613915] CrossrefMedlineGoogle Scholar
    • 5. Schwartz GGOlsson AGEzekowitz MDGanz POliver MFWaters Det al Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized, controlled trial. JAMA2001;285:1711-8. [PMID: 11277825] CrossrefMedlineGoogle Scholar
    • 6. Heeschen CHamm CWLaufs USnapinn SBohm MWhite HDet al Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation2002;105:1446-52. [PMID: 11914253] CrossrefMedlineGoogle Scholar
    • 7. Rationale and design of the GRACE (Global Registry of Acute Coronary Events) Project: a multinational registry of patients hospitalized with acute coronary syndromes. Am Heart J2001;141:190-9. [PMID: 11174331] CrossrefMedlineGoogle Scholar
    • 8. Fox KAGoodman SGKlein WBrieger DSteg PGDabbous Oet al Management of acute coronary syndromes. Variations in practice and outcome; findings from the Global Registry of Acute Coronary Events (GRACE). Eur Heart J2002;23:1177-89. [PMID: 12127920] CrossrefMedlineGoogle Scholar
    • 9. Steg PGGoldberg RJGore JMFox KAEagle KAFlather MDet al Baseline characteristics, management practices, and in-hospital outcomes of patients hospitalized with acute coronary syndromes in the Global Registry of Acute Coronary Events (GRACE). Am J Cardiol2002;90:358-63. [PMID: 12161222] CrossrefMedlineGoogle Scholar
    • 10. Spencer FASantopinto JJGore JMGoldberg RJFox KAMoscucci Met al Impact of aspirin on presentation and hospital outcomes in patients with acute coronary syndromes (The Global Registry of Acute Coronary Events [GRACE]). Am J Cardiol2002;90:1056-61. [PMID: 12423703] CrossrefMedlineGoogle Scholar
    • 11. Col NFYarzbski JGore JMAlpert JSGoldberg RJDoes aspirin consumption affect the presentation or severity of acute myocardial infarction? Arch Intern Med1995;155:1386-9. [PMID: 7794087] CrossrefMedlineGoogle Scholar
    • 12. Borzak SCannon CPKraft PLDouthat LBecker RCPalmeri STet al Effects of prior aspirin and anti-ischemic therapy on outcome of patients with unstable angina. TIMI 7 Investigators. Thrombin Inhibition in Myocardial Ischemia. Am J Cardiol1998;81:678-81. [PMID: 9527073] CrossrefMedlineGoogle Scholar
    • 13. Crisby MNordin-Fredriksson GShah PKYano JZhu JNilsson JPravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation2001;103:926-33. [PMID: 11181465] CrossrefMedlineGoogle Scholar
    • 14. Notarbartolo ADavi GAverna MBarbagallo CMGanci AGiammarresi Cet al Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscler Thromb Vasc Biol1995;15:247-51. [PMID: 7749833] CrossrefMedlineGoogle Scholar
    • 15. Hernandez-Perera OPerez-Sala DNavarro-Antolin JSanchez-Pascuala RHernandez GDiaz Cet 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 Invest1998;101:2711-9. [PMID: 9637705] CrossrefMedlineGoogle Scholar
    • 16. Fukumoto YLibby PRabkin EHill CCEnomoto MHirouchi Yet al Statins alter smooth muscle cell accumulation and collagen content in established atheroma of watanabe heritable hyperlipidemic rabbits. Circulation2001;103:993-9. [PMID: 11181475] CrossrefMedlineGoogle Scholar
    • 17. Lefer AMCampbell BShin YKScalia RHayward RLefer DJSimvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts. Circulation1999;100:178-84. [PMID: 10402448] CrossrefMedlineGoogle Scholar
    • 18. Endres MLaufs UHuang ZNakamura THuang PMoskowitz MAet al Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A1998;95:8880-5. [PMID: 9671773] CrossrefMedlineGoogle Scholar
    • 19. Hayashidani STsutsui HShiomi TSuematsu NKinugawa SIde Tet al Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation2002;105:868-73. [PMID: 11854129] CrossrefMedlineGoogle Scholar
    • 20. Laufs UWassmann SHilgers SRibaudo NBohm MNickenig GRapid effects on vascular function after initiation and withdrawal of atorvastatin in healthy, normocholesterolemic men. Am J Cardiol2001;88:1306-7. [PMID: 11728362] CrossrefMedlineGoogle Scholar
    • 21. Laufs UEndres MCustodis FGertz KNickenig GLiao JKet al Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation2000;102:3104-10. [PMID: 11120702] CrossrefMedlineGoogle Scholar
    • 22. Fonarow GCGawlinski AMoughrabi STillisch JHImproved treatment of coronary heart disease by implementation of a Cardiac Hospitalization Atherosclerosis Management Program (CHAMP). Am J Cardiol2001;87:819-22. [PMID: 11274933] CrossrefMedlineGoogle Scholar
    • 23. Stenestrand UWallentin LEarly statin treatment following acute myocardial infarction and 1-year survival. JAMA2001;285:430-6. [PMID: 11242427] CrossrefMedlineGoogle Scholar