Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs The CVD-REAL 2 Study

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:71

Article

Kosiborod, Mikhail^1,2  Lam, Carolyn S. P.^3,4,5  Kohsaka, Shun⁶  Kim, Dae Jung⁷  Karasik, Avraham⁸  Shaw, Jonathan⁹  Tangri, Navdeep¹⁰  Goh, Su-Yen¹¹  Thuresson, Marcus¹²  Chen, Hungta¹³  Surmont, Filip¹⁴  Hammar, Niklas^15,16  Fenici, Peter¹⁷ 

[1] St Lukes Mid Amer Heart Inst, Dept Cardiovasc Dis, Kansas City, MO USA

[2] Univ Missouri Kansas City, Kansas City, MO 64110 USA

[3] Natl Heart Ctr, Singapore, Singapore

[4] SingHlth Duke NUS, Singapore, Singapore

[5] Univ Med Ctr Groningen, Groningen, Netherlands

[6] Keio Univ, Sch Med, Dept Cardiol, Tokyo, Japan

[7] Ajou Univ, Sch Med, Dept Endocrinol & Metab, Suwon, South Korea

[8] Tel Aviv Univ & Maccabi Healthcare Israel, Inst Endocrinol, Tel Aviv, Israel

[9] Baker Heart & Diabet Inst, Clin & Populat Hlth, Melbourne, Vic, Australia

[10] Univ Manitoba, Dept Internal Med, Winnipeg, MB, Canada

[11] Singapore Gen Hosp, Dept Endocrinol, Singapore, Singapore

[12] Statisticon AB, Uppsala, Sweden

[13] AstraZeneca, Gaithersburg, MD USA

[14] AstraZeneca, Luton, Beds, England

[15] Karolinska Inst, Stockholm, Sweden

[16] AstraZeneca, Gothenburg, Sweden

[17] AstraZeneca, Cambridge, England

关键词: death;    diabetes mellitus;    heart failure;    observational studies;    sodium glucose cotransporter-2 inhibitors;    SGLT-2 inhibitor;   

DOI  :  10.1016/j.jacc.2018.03.009

来源: Elsevier

【 摘 要 】

BACKGROUND Randomized trials demonstrated a lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high CV risk. Prior real-world data suggested similar SGLT-2i effects in T2D patients with a broader risk profile, but these studies focused on heart failure and death and were limited to the United States and Europe. OBJECTIVES The purpose of this study was to examine a broad range of CV outcomes in patients initiated on SGLT-2i versus other glucose-lowering drugs (oGLDs) across 6 countries in the Asia Pacific, the Middle East, and North American regions. METHODS New users of SGLT-2i and oGLDs were identified via claims, medical records, and national registries in South Korea, Japan, Singapore, Israel, Australia, and Canada. Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching. Hazard ratios (HRs) for death, hospitalization for heart failure (HHF), death or HHF, MI, and stroke were assessed by country and pooled using weighted meta-analysis. RESULTS After propensity-matching, there were 235,064 episodes of treatment initiation in each group; w27% had established CV disease. Patient characteristics were well-balanced between groups. Dapagliflozin, empagliflozin, ipragliflozin, canagliflozin, tofogliflozin, and luseogliflozin accounted for 75%, 9%, 8%, 4%, 3%, and 1% of exposure time in the SGLT-2i group, respectively. Use of SGLT-2i versus oGLDs was associated with a lower risk of death (HR: 0.51; 95% confidence interval [CI]: 0.37 to 0.70; p < 0.001), HHF (HR: 0.64; 95% CI: 0.50 to 0.82; p = 0.001), death or HHF (HR: 0.60; 95% CI: 0.47 to 0.76; p < 0.001), MI (HR: 0.81; 95% CI: 0.74 to 0.88; p < 0.001), and stroke (HR: 0.68; 95% CI: 0.55 to 0.84; p < 0.001). Results were directionally consistent across both countries and patient subgroups, including those with and without CV disease. CONCLUSIONS In this large, international study of patients with T2D from the Asia Pacific, the Middle East, and North America, initiation of SGLT-2i was associated with a lower risk of CV events across a broad range of outcomes and patient characteristics. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

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