Ezetimibe added to statin therapy after acute coronary syndromes

IMPROVE-IT Investigators

Research output: Contribution to journalArticle

1637 Citations (Scopus)

Abstract

BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). Rates of pre-specified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit.

Original languageEnglish (US)
Pages (from-to)2387-2397
Number of pages11
JournalNew England Journal of Medicine
Volume372
Issue number25
DOIs
StatePublished - Jun 18 2015
Externally publishedYes

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Acute Coronary Syndrome
LDL Cholesterol
Therapeutics
Lipids
Ezetimibe
Unstable Angina
Intestinal Absorption
Random Allocation
Gallbladder
Stroke
Myocardial Infarction
Cholesterol
Placebos
Confidence Intervals
Muscles
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ezetimibe added to statin therapy after acute coronary syndromes. / IMPROVE-IT Investigators.

In: New England Journal of Medicine, Vol. 372, No. 25, 18.06.2015, p. 2387-2397.

Research output: Contribution to journalArticle

IMPROVE-IT Investigators. / Ezetimibe added to statin therapy after acute coronary syndromes. In: New England Journal of Medicine. 2015 ; Vol. 372, No. 25. pp. 2387-2397.
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abstract = "BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7{\%} in the simvastatin-ezetimibe group, as compared with 34.7{\%} in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95{\%} confidence interval, 0.89 to 0.99; P = 0.016). Rates of pre-specified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit.",
author = "{IMPROVE-IT Investigators} and Cannon, {Christopher P.} and Blazing, {Michael A.} and Giugliano, {Robert P.} and Amy McCagg and White, {Jennifer A.} and Pierre Theroux and Harald Darius and Lewis, {Basil S.} and Ophuis, {Ton Oude} and Jukema, {J. Wouter} and {De Ferrari}, {Gaetano M.} and Witold Ruzyllo and {De Lucca}, Paul and Im, {Kyung Ah} and Bohula, {Erin A.} and Craig Reist and Wiviott, {Stephen D.} and Tershakovec, {Andrew M.} and Musliner, {Thomas A.} and Eugene Braunwald and Califf, {Robert M.} and T. Musliner and A. Tershakovec and E. Gurfinkel and P. Aylward and A. Tonkin and G. Maurer and {Van de Werf}, F. and JC Nicolau and J. Genest and P. Armstrong and R. Corbalan and D. Isaza and J. Spinar and P. Grande and J. Voitk and A. Kesaniemi and JP Bassand and M. Farnier and M. Keltai and A. Mathur and S. Mittal and K. Reddy and H. White and T. Pedersen and F. Britto and M. Carrageta and T. Duris and A. Dalby and Garcia, {Mario J.}",
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TY - JOUR

T1 - Ezetimibe added to statin therapy after acute coronary syndromes

AU - IMPROVE-IT Investigators

AU - Cannon, Christopher P.

AU - Blazing, Michael A.

AU - Giugliano, Robert P.

AU - McCagg, Amy

AU - White, Jennifer A.

AU - Theroux, Pierre

AU - Darius, Harald

AU - Lewis, Basil S.

AU - Ophuis, Ton Oude

AU - Jukema, J. Wouter

AU - De Ferrari, Gaetano M.

AU - Ruzyllo, Witold

AU - De Lucca, Paul

AU - Im, Kyung Ah

AU - Bohula, Erin A.

AU - Reist, Craig

AU - Wiviott, Stephen D.

AU - Tershakovec, Andrew M.

AU - Musliner, Thomas A.

AU - Braunwald, Eugene

AU - Califf, Robert M.

AU - Musliner, T.

AU - Tershakovec, A.

AU - Gurfinkel, E.

AU - Aylward, P.

AU - Tonkin, A.

AU - Maurer, G.

AU - Van de Werf, F.

AU - Nicolau, JC

AU - Genest, J.

AU - Armstrong, P.

AU - Corbalan, R.

AU - Isaza, D.

AU - Spinar, J.

AU - Grande, P.

AU - Voitk, J.

AU - Kesaniemi, A.

AU - Bassand, JP

AU - Farnier, M.

AU - Keltai, M.

AU - Mathur, A.

AU - Mittal, S.

AU - Reddy, K.

AU - White, H.

AU - Pedersen, T.

AU - Britto, F.

AU - Carrageta, M.

AU - Duris, T.

AU - Dalby, A.

AU - Garcia, Mario J.

PY - 2015/6/18

Y1 - 2015/6/18

N2 - BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). Rates of pre-specified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit.

AB - BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). Rates of pre-specified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit.

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U2 - 10.1056/NEJMoa1410489

DO - 10.1056/NEJMoa1410489

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EP - 2397

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

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