IMPROVE‑ IT studies in patients with diabetes mellitus

Czech version

Authors: J. Špinar ^1,2; L. Špinarová ³; J. Vítovec ³
Authors‘ workplace: Interní kardiologická klinika LF MU a FN Brno ¹; Mezinárodní centrum klinického výzkumu, FN u sv. Anny v Brně ²; I. interní kardioangiologická klinika LF MU a FN u sv. Anny v Brně ³
Published in: Kardiol Rev Int Med 2015, 17(3): 253-256
Category: Cardiology Review

Overview

The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE‑ IT) is evaluating the potential benefit for reduction of major cardiovascular events from the addition of ezetimibe vs. placebo to 40 mg/ d of simvastatin therapy in patients who present with acute coronary syndromes and have low‑ density lipoprotein cholesterol ≤ 125 mg/ dL. 18,144 patients were enrolled with either ST‑segment elevation MI (STEMI, n = 5,192) or UA/ non‑ST‑segment elevation MI (UA/ NSTEMI, n = 12,952). Primary endpoint occurred in 2,742 patients (34.7%) treated with simvastatin in monotherapy and in 2,572 patients (32.7%) (p = 0.016) treated with combination. Compared to patients with coronary heart disease given the drug simvastatin plus a placebo, those given both simvastatin and the non‑statin drug, ezetimibe, had a 6.4 percent lower combined risk of subsequent heart attack, stroke, cardiovascular death, rehospitalisation for unstable angina and procedures to restore blood flow to the heart. Heart attacks alone were reduced by 13%, and non‑fatal stroke by 20%. Deaths from cardiovascular disease were statistically the same in both groups. Approximately two patients out of every 100 patients treated for seven years avoided a heart attack or stroke. (Number Needed to Treat (NNT) = 50/ 7 years). The results of sub analysis of the IMPROVE IT study with diabetics n = 4.933 (27%) were presented on European Cardiology Congress in London 2015 Diabetics were older, more frequently female and less frequently smoker. The baseline lipid values and the changes did not differ. The most important finding was the effect on myocardial infarction and on ischemic stroke (values in %/ 7years). Myocardial infarction appeared in nodiabetics in 12.7 (S) vs. 12.0 (S/ E) and in u diabetics 20.8 (S) vs. 16.4 (/ E), p = 0.002 and for ischemic stroke nondiabetics 3.4 (S) vs. 3.2 (S/ E) and diabetics 6.5 (S) vs. 3.8 (S/ E) p = 0.031.

Conclusion:
Patients with diabetes mellitus have a higher profit from adding ezetimibe to statin and this effect is not explainable by lipid changes.

Keywords:
acute coronary syndrome – LDL cholesterol – combination therapy – ezetimibe – diabetes mellitus

Sources

1. Cannon CP, Blazing MA, Giugliano RP et al. The IMPROVE‑ IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372: 387– 397. doi: 10.1056/ NEJMoa1410489.

2. Jarcho JA, Keaney JF. Proof That Lower Is Better –LDL Cholesterol and IMPROVE‑ IT. N Engl J Med 20015; 372: 2448– 2450. doi: 10.1056/ NEJMe1507041.

3. Špinar J, Špinarová L, Vítovec J. Improve-IT změní guidelines. Kardiol Rev Int Med 2014; 16: 71– 74.

4. Giugliano RP, Canon CP, Blazing MA et al. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in partients with vs. without diabetes: the IPMROVE‑ IT Trial. Eur Heart J.In press 2015.