Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2018; 9(12): 252-257
Published online Dec 15, 2018. doi: 10.4239/wjd.v9.i12.252
Using real world data to assess cardiovascular outcomes of two antidiabetic treatment classes
Manfred Paul Stapff
Manfred Paul Stapff, CMO, TriNetX Inc., Cambridge, MA 02140, United States
Author contributions: Stapff MP developed the scientific concept, literature search, study design, applied the data querying, result interpretation, scientific discussion, and prepared the manuscript.
Institutional review board statement: As a federated network TriNetX received a waiver from Western IRB since only aggregated counts, statistical summaries of de-identified information, but no protected health information is received, and no study specific activities are performed in retrospective analyses.
Informed consent statement: This was an observational study based on analyses of anonymized electronic medical records describing real world treatment. No intervention or any study specific activity was done. Therefore, no informed consent was necessary and would even have been not feasible considering the anonymized and retrospective character of the analysis.
Conflict-of-interest statement: The author is employee of TriNetX Inc., the data network and analytics platform used for this publication. TriNetX as a company was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. The author does not declare conflicting interests (including but not limited to commercial, personal, political, intellectual, or religious interests).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Manfred Paul Stapff, MD, PhD, Chief Medical Officer, CMO, TriNetX Inc., 125 Cambridgepark Drive, Ste 500, Cambridge, MA 02140, United States. manfred.stapff@trinetx.com
Telephone: +1-857-2856043
Received: August 22, 2018
Peer-review started: August 22, 2018
First decision: October 4, 2018
Revised: October 10, 2018
Accepted: November 15, 2018
Article in press: November 15, 2018
Published online: December 15, 2018
Abstract
AIM

To evaluate the effect on cardiovascular outcomes of sodium-glucose co-transporter-2 (SGLT2) inhibitors in a real world setting by analyzing electronic medical records.

METHODS

We used TriNetX, a global federated research network providing statistics on electronic health records (EHR). The analytics subset contained EHR from approximately 38 Million patients in 35 Health Care Organizations in the United States. The records of 46,909 patients who had taken SGLT2 inhibitors were compared to 189,120 patients with dipeptidyl peptidase (DPP) 4 inhibitors. We identified five potential confounding factors and built respective strata: elderly, hypertension, chronic kidney disease (CKD), and co-medication with either insulin or metformin. Cardiovascular events were counted as stroke (ICD10 code: I63) or myocardial infarction (ICD10: I21) occurring within three years after the first instance of the respective medication in the patients’ records.

RESULTS

Of the 46909 patients with SGLT2 inhibitors in their EHR, 1667 patients (3.6%) had an ICD code for stroke or for myocardial infarction within the first three years after the first instance of the medication. In the control group, there were 10680 events of 189120 patients (5.6%), which represents a risk ratio of 0.63 (95%CI: 0.60-0.66). The overall incidence of stroke or myocardial infarction in the strata with a potential confounding risk factor reached from 4.9% in patients taking metformin to 12.5% in the stratum with the highest risk (concomitant CKD). In all strata, the difference in risk of experiencing a cardiovascular event was similarly in favor of SGLT2 vs control, with Risk Ratio ranging from 0.62 to 0.81.

CONCLUSION

Real world data replicated the results from randomized clinical trials, confirmed the cardiovascular advantages of SGLT2 inhibitors, and showed its applicability to the US population.

Keywords: Sodium-glucose co-transporter-2 inhibitors, Cardiovascular events, Clinical trials, Electronic medical records, Dipeptidyl peptidase 4 inhibitors, Real world evidence, Diabetes

Core tip: Cardiovascular advantages of sodium-glucose co-transporter-2 (SGLT2) inhibitors were shown in complex clinical trials or in countries with large registries. However, it was unclear whether these findings could be applied to routine medical practice in the US. This real world analysis from 46909 patients with SGLT2 inhibitors revealed a 0.63 (95%CI: 0.60-0.66) risk ratio of SGLT2 inhibitors compared to 189120 patients with dipeptidyl peptidase 4 inhibitors. This analysis of electronic health records could replicate the results of randomized clinical trials, which supports the usefulness of such real world studies (e.g., for long-term outcome or safety observations).