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Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs

2018; Elsevier BV; Volume: 71; Issue: 23 Linguagem: Inglês

10.1016/j.jacc.2018.03.009

1558-3597

Mikhail Kosiborod, Carolyn S.P. Lam, Shun Kohsaka, Dae Jung Kim, Avraham Karasik, Jonathan E. Shaw, Navdeep Tangri, Su‐Yen Goh, Marcus Thuresson, Hungta Chen, Filip Surmont, Niklas Hammar, Peter Fenici, Mikhail Kosiborod, Matthew A. Cavender, Alex Z. Fu, John Wilding, Kamlesh Khunti, Anna Norhammar, Kåre I. Birkeland, Marit E. Jørgensen, Reinhard W. Holl, Carolyn S.P. Lam, Hanne Løvdal Gulseth, Bendix Carstensen, Esther Bollow, Josep Franch‐Nadal, Luis A. Garcı́a Rodrı́guez, Avraham Karasik, Navdeep Tangri, Shun Kohsaka, Dae Jung Kim, Jonathan E. Shaw, Suzanne V. Arnold, Su‐Yen Goh, Niklas Hammar, Peter Fenici, Johan Bodegård, Hungta Chen, Filip Surmont, Kyle Nahrebne, Betina T. Blak, Eric Wittbrodt, Matthias Saathoff, Yusuke Noguchi, Donna Tan, Maro R. I. Williams, Hye Won Lee, Maya Greenbloom, Oksana Kaidanovich‐Beilin, Khung Keong Yeo, Yong Mong Bee, Joan Khoo, Agnes Koong, Yee How Lau, Fei Gao, Wee Boon Tan, Hanis Abdul Kadir, Kyoung Hwa Ha, Jinhee Lee, Gabriel Chodick, Cheli Melzer Cohen, Reid Whitlock, Lucía Cea Soriano, Oscar Fernándex Cantero, Ellen Riehle, Jenni Ilomäki, Dianna J. Magliano,

Diabetes Management and Research

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.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.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.After propensity-matching, there were 235,064 episodes of treatment initiation in each group; ∼27% 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.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. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614).