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.

IMPROVE-IT

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

PRESENTATIONS

Main Study Results (Cannon, AHA 2014)
On-Treatment Analysis (AHA 2014)

Total Events (Murphy, ACC 2015)

hsTnt (Qamar, AHA 2017)

Biomarkers (Qamar, AHA 2017) Association of Genetic Risk Score with Risk of Recurrent Coronary Events in IMPROVE-IT (Ruff, AHA 2018)
Ezetimibe Consistently Reduces LDL-C with Little Interindividual Variability in 14,970 Patients Post-ACS (Patel, AHA 2021)
Risk of Major Adverse Limb Events with Ezetimibe versus Placebo in Addition to Statin Therapy-Insights from the IMPROVE IT Trial (Bonaca, ESC 2023)

OTHER 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.

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.

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.

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.

Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA. 2016 Sep 27;316(12):1289-97.

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.

Long-term Safety and Efficacy of Achieving Very Low Levels of Low-Density Lipoprotein Cholesterol : A Prespecified Analysis of the IMPROVE-IT Trial. JAMA Cardiol. 2017 May 1;2(5):547-555.

Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function. J Am Soc Nephrol. 2017 Oct;28(10):3034-3043. doi: 10.1681/ASN.2016090957. Epub 2017 May 15.

Competing Risks of Cardiovascular Versus Noncardiovascular Death During Long-Term Follow-Up After Acute Coronary Syndromes. J Am Heart Assoc. 2017 Sep 18;6(9):e005840.

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.

Efficacy and Safety of Adding Ezetimibe to Statin Therapy Among Women and Men: Insight From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). J Am Heart Assoc. 2017 Nov 18;6(11):e006901.

Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus: Results From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation. 2018 Apr 10;137(15):1571-1582.

Natural History of Patients Postacute Coronary Syndrome Based on Heart Failure Status. Am J Cardiol. 2018 Nov 1;122(9):1451-1458. doi: 10.1016/j.amjcard.2018.07.034. Epub 2018 Aug 4.

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.

Efficacy and Safety of Further Lowering of Low-Density Lipoprotein Cholesterol in Patients Starting With Very Low Levels: A Meta-analysis. JAMA Cardiol. 2018 Sep 1;3(9):823-828.

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.

Medication Discontinuation in the IMPROVE-IT Trial. Circ Cardiovasc Qual Outcomes. 2019 Jan;12(1):e005041.

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.

Outcomes of Women Compared With Men After Non-ST-Segment Elevation Acute Coronary Syndromes. J Am Coll Cardiol. 2019 Dec 17;74(24):3013-3022.

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

Prospective Evaluation of Malignancy in 17,708 Patients Randomized to Ezetimibe Versus Placebo: Analysis From IMPROVE-IT. JACC CardioOncol. 2020 Sep 15;2(3):385-396.

Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020 Nov 21;396(10263):1637-1643.

Sex, Permanent Drug Discontinuation, and Study Retention in Clinical Trials: Insights From the TIMI trials. Circulation. 2021 Feb 16;143(7):685-695.

Baseline Low-Density Lipoprotein Cholesterol and Clinical Outcomes of Combining Ezetimibe With Statin Therapy in IMPROVE-IT. J Am Coll Cardiol. 2021 Oct 12;78(15):1499-1507.

Reply: Analyzing IMPROVE-IT Beyond LDL Cholesterol. J Am Coll Cardiol. 2022 Feb 1;79(4):e153. doi: 10.1016/j.jacc.2021.11.018.

Cardiovascular Events and Long-Term Risk of Sudden Death Among Stabilized Patients After Acute Coronary Syndrome: Insights From IMPROVE-IT. J Am Heart Assoc. 2022 Feb 15;11(4):e022733.

Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients Stabilized After Acute Coronary Syndrome: A Secondary Analysis From IMPROVE-IT. JAMA Cardiol. 2022 Dec 1;7(12):1199-1206.

Benefit of Combination Ezetimibe/Simvastatin Among High-Risk Populations: Lessons from the IMPROVE-IT Trial. Curr Atheroscler Rep. 2023 Mar;25(3):85-93.

Impact of Ezetimibe on New-Onset Diabetes: A Substudy of IMPROVE-IT. J Am Heart Assoc. 2023 Jun 22:e029593. doi: 10.1161/JAHA.122.029593.

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