IMPROVE-IT (TIMI 40)

IMPROVE-IT (TIMI 40) determined whether the addition of ezetimibe to statin therapy, using ezetimibe/simvastatin, improves cardiovascular outcomes compared with simvastatin monotherapy in patients after ACS. In addition, the difference in achieved LDL-C levels between the groups provided data on whether the target for LDL-C lowering should be reduced further.

MAIN RESULTS:
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
N Engl J Med. 2015 Jun 18;372(25):2387-97.

MAIN RESULTS PRESENTATION

PUBLICATIONS

Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J. 2008 Nov;156(5):826-32.

An update on the IMProved reduction of outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) design. Am Heart J. 2010 May;159(5):705-9.

Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population. Am Heart J. 2014 Aug;168(2):205-12.e1.

Baseline LDL-C And Clinical Outcomes With Addition Of Ezetimibe To Statin In 18,144 Patients Post ACS. J Am Coll Cardiol. 2015 Mar, 65 (10_Supplement) A4.

Risk Stratification For Cardiovascular Events In The IMPROVE-IT Trial. J Am Coll Cardiol. 2015 Mar, 65 (10_Supplement) A3.

Achievement of Dual Low-Density Lipoprotein Cholesterol and High-Sensitivity C-Reactive Protein Targets More Frequent With the Addition of Ezetimibe to Simvastatin and Associated With Better Outcomes in IMPROVE-IT. Circulation. 2015 Sep 29;132(13):1224-33.

Increasing Age and the Benefit From Higher-intensity Lipid Lowering With Ezetimibe/Simvastatin vs. Simvastatin Alone: Results From the IMPROVE-IT Trial. Circulation. November 10, 2015; Vol 132, Issue suppl_3.

Impact of Ezetimibe on Hospitalization-Related Costs Among Patients With a Recent Acute Coronary Syndrome: Results From the IMPROVE-IT Trial. November 10, 2015; Vol 132, Issue suppl_3.

Fatty Liver Index is Reduced With Ezetimibe in an Analysis of 15,095 Patients Randomized to Ezetimibe vs Placebo in the Improve-it Trial. November 10, 2015; Vol 132, Issue suppl_3.

Reduction in Non-hemorrhagic Stroke With Ezetimibe/Simvastatin Compared With Simvastatin Alone in the IMPROVE-IT Trial. November 10, 2015; Vol 132, Issue suppl_3.

Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial. J Am Coll Cardiol. 2016 Feb 2;67(4):353-361.

Response to Letter Regarding Article, “Achievement of Dual Low-Density Lipoprotein Cholesterol and High-Sensitivity C-Reactive Protein Targets More Frequent With the Addition of Ezetimibe to Simvastatin and Associated With Better Outcomes in IMPROVE-IT”. Circulation. 2016 Mar 29;133(13):e463.

Long Term Significance Of Heart Failure Complicating Acute Myocardial Infarction In 11,185 Patients From The Improved Reduction Of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). J Am Coll Cardiol. 2016 Apr, 67 (13_Supplement) 484.

The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial. Eur Heart J. 2016 Dec 21;37(48):3576-3584.

On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). Am Heart J. 2016 Dec;182:89-96.

Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention. J Am Coll Cardiol. 2017 Feb 28;69(8):911-921.

Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and Associated Costs Among Patients With a Recent Acute Coronary Syndrome: Results From the IMPROVE-IT Trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circ Cardiovasc Qual Outcomes. 2017 May;10(5):e003201.

Prevention of Stroke with the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation. 2017 Dec 19;136(25):2440-2450.

Association of Type of Presentation, STEMI vs NSTEMI/UA, With the Relative Long-Term Incidence of Cardiovascular and Non-Cardiovascular Mortality. November 11, 2016; Vol 134, Issue suppl_1.

The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe. Int J Cardiol. 2018 Nov 1;270:245-252.

Response by Bohula et al to Letters Regarding Article, “Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)”. Circulation. 2018 Jun 12;137(24):2662-2663.

Polyvascular Disease, Diabetes Mellitus And Long-Term Vascular Risk: Insights From The IMPROVE-IT TIMI 40 Trial. Lancet Diabetes Endocrinol. 2018 Dec;6(12):934-943.

Biomarkers and Clinical Cardiovascular Outcomes With Ezetimibe in the IMPROVE-IT Trial. J Am Coll Cardiol. 2019 Aug 27;74(8):1057-1068.

Effect of Simvastatin-Ezetimibe Compared With Simvastatin Monotherapy After Acute Coronary Syndrome Among Patients 75 Years or Older: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2019 Sep 1;4(9):846-854.

Muscle Complaints or Events in Patients Randomized to Simvastatin or Ezetimibe/Simvastatin. J Am Coll Cardiol. 2020 Feb 25;75(7):835-837.