Implications for Ezetimibe Therapy Use Based on IMPROVE-IT Criteria - 22/10/15

Doi : 10.1016/j.amjmed.2015.05.027

Salim S. Virani, MD, PhD ^a,^b,^c,^d,^e,^⁎ , Julia M. Akeroyd, MPH ^a,^b, Vijay Nambi, MD, PhD ^c,^d,^e, Thomas M. Maddox, MD, MSc ^f, Michael A. Gillette, PharmD ^c, P. Michael Ho, MD, PhD ^f, John Rumsfeld, MD, PhD ^f, Laura A. Petersen, MD, MPH ^a,^b, Christie M. Ballantyne, MD ^d,^e
^a Health Policy, Quality & Informatics Program, Michael E. DeBakey Veterans Affairs Medical Center Health Services Research and Development Center for Innovations, Houston, Tex
^b Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Tex
^c Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Tex
^d Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Tex
^e Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, Tex
^f Veterans Affairs Eastern Colorado Health Care System, Denver

^∗Requests for reprints should be addressed to Salim S. Virani, MD, PhD, Health Services Research and Development (152), Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Blvd, Houston, TX 77030.

Abstract

Purpose

In the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), simvastatin/ezetimibe combination was associated with a 6% relative risk reduction in the combined cardiovascular outcome compared with simvastatin alone in patients with acute coronary syndrome. Given strict inclusion criteria (low-density lipoprotein cholesterol 50-125 mg/dL and no use of statins more potent than simvastatin 40 mg), the implications of this important trial in routine acute coronary syndrome care are unknown.

Methods

We identified patients with acute coronary syndrome from the Veterans Affairs health care system over a 5-year period and determined what proportion would be candidates for ezetimibe on the basis of IMPROVE-IT criteria. We then evaluated what proportion could potentially see an increase in ezetimibe use if IMPROVE-IT criteria are not strictly followed.

Results

Of 219,625 patients with acute coronary syndrome, 69,508 (31.6%) would qualify for ezetimibe on the basis of strict criteria. Among those who did not meet IMPROVE-IT criteria (n = 150,117), ezetimibe could potentially be prescribed by clinicians in a further 28% of patients (n = 61,635) using statins more potent than simvastatin 40 mg, 7.1% of patients (15,527) with a documented statin intolerance, and 10.4% of patients (22,758) with low-density lipoprotein cholesterol >125 mg/dL.

Conclusions

Our results provide a first look at the implications of this trial in a large health care system. Although 31.6% of patients would qualify for ezetimibe, there is a large potential for an increase in ezetimibe use in acute coronary syndrome outside of the strict trial inclusions. These findings call for a discussion on ezetimibe's role in patients with acute coronary syndrome already taking high-intensity statins or those with statin intolerance.

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Keywords : Ezetimibe, IMPROVE-IT, Moderate- to high-intensity statin therapy, Treatment practice

Plan

Materials and Methods

	Funding: SSV and TMM are supported by a Department of Veterans Affairs Health Services Research and Development Service Career Development Award. SSV is also supported by American Heart Association Beginning Grant-in-Aid (14BGIA20460366) and the American Diabetes Association Clinical Science and Epidemiology award (1-14-CE-44). This work was also supported by the Houston Veterans Affairs Health Services Research and Development Center for Innovations Grant HFP 90-020.
	Conflict of Interest: VN is a national monitor for a study sponsored by Anthera; is on the regional advisory board of Sanofi Regeneron; and has a research collaboration with TomTec and a provisional patent: “Biomarkers to Improve Prediction of Heart Failure Risk” (Patent No. 61721475) filed by Baylor College of Medicine and Roche. CMB received grant and research support (all paid to the institution, not the individual) from Abbott Diagnostics, Amarin, Amgen, Eli Lilly, Esperion, Novartis, Otsuka, Pfizer, Regeneron, Roche Diagnostics, Sanofi-Synthelabo, National Institutes of Health, American Diabetes Association, and American Heart Association; is a consultant to Abbott Diagnostic, Amarin, Amgen, AstraZeneca, Eli Lilly, Esperion, Genzyme, Merck, Novartis, Pfizer, Regeneron, Roche, and Sanofi-Synthelabo; and has a provisional patent: “Biomarkers to Improve Prediction of Heart Failure Risk” (Patent No. 61721475) filed by Baylor College of Medicine and Roche.
	Authorship: All authors had access to the data and played a role in writing this manuscript.