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J Am Coll Cardiol. 2018 Jun 12;71(23):2628-2639. doi: 10.1016/j.jacc.2018.03.009. Epub 2018 Mar 11.

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

Author information

1
Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, Missouri. Electronic address: mkosiborod@saint-lukes.org.
2
National Heart Centre, Singapore and SingHealth Duke-NUS, Singapore; University Medical Centre Groningen, Groningen, the Netherlands.
3
Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
4
Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea.
5
Institute of Endocrinology, Tel Aviv University and Maccabi Healthcare Israel, Tel Aviv, Israel.
6
Clinical and Population Health, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
7
Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
8
Department of Endocrinology, Singapore General Hospital, Singapore.
9
Statisticon AB, Uppsala, Sweden.
10
AstraZeneca, Gaithersburg, Maryland.
11
AstraZeneca, Luton, United Kingdom.
12
Karolinska Institutet, Stockholm, Sweden; AstraZeneca, Gothenburg, Sweden.
13
AstraZeneca, Cambridge, United Kingdom.

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

PMID:
29540325
DOI:
10.1016/j.jacc.2018.03.009
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