Circulation. 2002;105:1446-1452
Published online before print March 4, 2002, doi: 10.1161/01.CIR.0000012530.68333.C8
Published online before print March 4, 2002, doi: 10.1161/01.CIR.0000012530.68333.C8
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(Circulation. 2002;105:1446.)
© 2002 American Heart Association, Inc.
Withdrawal of Statins Increases Event Rates in Patients With Acute Coronary Syndromes
From University Hospital Frankfurt, Germany (C.H.); Kerckhoff Heart Center, Bad Nauheim, Germany (C.W.H.); University Hospital Homburg (Saar), Germany (U.L., M.B.); Merck Research Laboratories, West Point, Pa (S.S.); and Green Lane Hospital, Auckland, New Zealand (H.D.W.).
Correspondence to Prof Christian W. Hamm, Kerckhoff Heart Center, Benekestrasse 2-8, 61231 Bad Nauheim, Germany. E-mail Christian.hamm{at}kerckhoff.med.uni-giessen.de
Background— HMG-CoA Reductase Inhibitors (statins) reduce cardiac event rates in patients with stable coronary heart disease. Withdrawal of chronic statin treatment during acute coronary syndromes may impair vascular function independent of lipid-lowering effects and thus increase cardiac event rate.
Methods and Results— We investigated the effects of statins on the cardiac event rate in 1616 patients of the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study who had coronary artery disease and chest pain in the previous 24 hours. We recorded death and nonfatal myocardial infarction during the 30-day follow-up. Baseline clinical characteristics did not differ among 1249 patients without statin therapy, 379 patients with continued statin therapy, and 86 patients with discontinued statin therapy after hospitalization. Statin therapy was associated with a reduced event rate at 30-day follow-up compared with patients without statins (adjusted hazard ratio, 0.49 [95% CI, 0.21 to 0.86]; P=0.004). If the statin therapy was withdrawn after admission, cardiac risk increased compared with patients who continued to receive statins (2.93 [95% CI, 1.64 to 6.27]; P=0.005) and tended to be higher compared with patients who never received statins (1.69 [95% CI, 0.92 to 3.56]; P=0.15). This was related to an increased event rate during the first week after onset of symptoms and was independent of cholesterol levels. In a multivariate model, troponin T elevation (P=0.005), ST changes (P=0.02), and continuation of statin therapy (P=0.008) were the only independent predictors of patient outcome.
Conclusions— Statin pretreatment in patients with acute coronary syndromes is associated with improved clinical outcome. However, discontinuation of statins after onset of symptoms completely abrogates this beneficial effect.
Key Words: angina • coronary disease • statins • ischemia • prognosis
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 O. Schouten, E. Boersma, S. E. Hoeks, R. Benner, H. van Urk, M. R.H.M. van Sambeek, H. J.M. Verhagen, N. A. Khan, M. Dunkelgrun, J. J. Bax, et al. Fluvastatin and Perioperative Events in Patients Undergoing Vascular Surgery N. Engl. J. Med., September 3, 2009; 361(10): 980 - 989. [Abstract] [Full Text] [PDF]
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|
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|
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|
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|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
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|
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|
|
|
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|
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|
|
|
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|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
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|
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|
|
|
|
 |
|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
F.M Sacks Do statins play a role in the early management of the acute coronary syndrome? Eur. Heart J. Suppl., March 1, 2004; 6(suppl_A): A32 - A36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
D. J. Kereiakes Adjunctive Pharmacotherapy before Percutaneous Coronary Intervention in Non-ST-Elevation Acute Coronary Syndromes: The Role of Modulating Inflammation Circulation, October 21, 2003; 108(90161): III-22 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Braunwald Application of Current Guidelines to the Management of Unstable Angina and Non-ST-Elevation Myocardial Infarction Circulation, October 21, 2003; 108(90161): III-28 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Piek and R. J. de Winter Type II secretory phospholipase A2: The emerging role of biochemical markers of plaque inflammation Eur. Heart J., October 2, 2003; 24(20): 1804 - 1806. [Full Text] [PDF]
|
|
|
|
 |
|
 W. S. Aronow Review Article: Treatment of Unstable Angina Pectoris/Non-ST-Segment Elevation Myocardial Infarction in Elderly Patients J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2003; 58(10): M927 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 J Cramer Medicine partnerships Heart, May 1, 2003; 89(90002): ii19 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Laufs and J. K. Liao Rapid Effects of Statins: From Prophylaxis to Therapy for Ischemic Stroke Arterioscler Thromb Vasc Biol, February 1, 2003; 23(2): 156 - 157. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
A.H Liem, A.J van Boven, N.J.G.M Veeger, A.J Withagen, R.M Robles de Medina, J.G.P Tijssen, and D.J van Veldhuisen Effect of fluvastatin on ischaemia following acute myocardial infarction: a randomized trial Eur. Heart J., December 2, 2002; 23(24): 1931 - 1937. [Abstract] [PDF]
|
|
|
|
|
|
J. Herrmann, A. Lerman, D. Baumgart, L. Volbracht, R. Schulz, C. von Birgelen, M. Haude, G. Heusch, and R. Erbel Preprocedural Statin Medication Reduces the Extent of Periprocedural Non-Q-Wave Myocardial Infarction Circulation, October 22, 2002; 106(17): 2180 - 2183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Lefer Statins as Potent Antiinflammatory Drugs Circulation, October 15, 2002; 106(16): 2041 - 2042. [Full Text] [PDF]
|
|
|
|
|
|
J. K. Plenge, T. L. Hernandez, K. M. Weil, P. Poirier, G. K. Grunwald, S. M. Marcovina, and R. H. Eckel Simvastatin Lowers C-Reactive Protein Within 14 Days: An Effect Independent of Low-Density Lipoprotein Cholesterol Reduction Circulation, September 17, 2002; 106(12): 1447 - 1452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C Fonarow Treating to goal: new strategies for initiating and optimizing lipid-lowering therapy in patients with atherosclerosis Vascular Medicine, August 1, 2002; 7(3): 187 - 194. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Vecchione and R. P. Brandes Withdrawal of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Elicits Oxidative Stress and Induces Endothelial Dysfunction in Mice Circ. Res., July 26, 2002; 91(2): 173 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Jackevicius, M. Mamdani, and J. V. Tu Adherence With Statin Therapy in Elderly Patients With and Without Acute Coronary Syndromes JAMA, July 24, 2002; 288(4): 462 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. B. Applegate Elderly Patients' Adherence to Statin Therapy JAMA, July 24, 2002; 288(4): 495 - 497. [Full Text] [PDF]
|
|
|
|
 |
|
 J. R Chiong and A. B Miller Review: Renin-angiotensin system antagonism and lipid-lowering therapy in cardiovascular risk management Journal of Renin-Angiotensin-Aldosterone System, June 1, 2002; 3(2): 96 - 102. [Abstract] [PDF]
|
|