Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study - PubMed (original) (raw)
Randomized Controlled Trial
. 2018 Jun 12;71(23):2628-2639.
doi: 10.1016/j.jacc.2018.03.009. Epub 2018 Mar 11.
Carolyn S P Lam 2, Shun Kohsaka 3, Dae Jung Kim 4, Avraham Karasik 5, Jonathan Shaw 6, Navdeep Tangri 7, Su-Yen Goh 8, Marcus Thuresson 9, Hungta Chen 10, Filip Surmont 11, Niklas Hammar 12, Peter Fenici 13; CVD-REAL Investigators and Study Group
Collaborators, Affiliations
- PMID: 29540325
- DOI: 10.1016/j.jacc.2018.03.009
Free article
Randomized Controlled Trial
Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study
Mikhail Kosiborod et al. J Am Coll Cardiol. 2018.
Free article
Abstract
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; ∼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.
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. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614).
Keywords: SGLT-2 inhibitor; death; diabetes mellitus; heart failure; observational studies; sodium glucose cotransporter-2 inhibitors.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Comment in
- Cardioprotection: SGLT2 blockers in T2DM.
Barranco C. Barranco C. Nat Rev Cardiol. 2018 May;15(5):255. doi: 10.1038/nrcardio.2018.35. Epub 2018 Mar 29. Nat Rev Cardiol. 2018. PMID: 29593287 No abstract available. - Only Trials Tell the Truth About Treatment Effects.
McMurray JJV. McMurray JJV. J Am Coll Cardiol. 2018 Jun 12;71(23):2640-2642. doi: 10.1016/j.jacc.2018.04.019. J Am Coll Cardiol. 2018. PMID: 29880123 No abstract available.
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