Gender differences in cardiovascular risk, treatment, and outcomes: a post hoc analysis from the REWIND trial

Abstract

Objectives. To assess whether the use of cardioprotective therapies for type 2 diabetes varies by gender and whether the risk of cardiovascular events is higher in women versus men in the REWIND trial, including an international type 2 diabetes patient population with a wide range of baseline risk. Design. Gender differences in baseline characteristics, cardioprotective therapy, and the achieved clinical targets at baseline and two years were analyzed. Hazards for cardiovascular outcomes (fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, cardiovascular death, all-cause mortality, and heart failure hospitalization), in women versus men were analyzed using two Cox proportional hazard models, adjusted for randomized treatment and key baseline characteristics respectively. Time-to-event analyses were performed in subgroups with or without history of cardiovascular disease using Cox proportional hazards models that included gender, subgroup, randomized treatment, and gender-by-subgroup interactions. Results. Of 9901 participants, 46.3% were women. Significantly fewer women than men had a cardiovascular disease history. Although most women met treatment targets for blood pressure (96.7%) and lipids (72.8%), fewer women than men met the target for cardioprotective therapies at baseline and after two years, particularly those with prior cardiovascular disease, who used less renin-angiotensin-aldosterone system inhibitors, statins, and aspirin than men. Despite these differences, women had lower hazards than men for all outcomes except stroke. No significant gender and cardiovascular disease history interactions were identified for cardiovascular outcomes. Conclusions. In REWIND, most women met clinically relevant treatment targets, but in lower proportions than men. Women had a lower risk for all cardiovascular outcomes except stroke.

Clinical trials.gov registration number: NCT01394952

Keywords:

• Gender differences
• risk factor management
• diabetes
• cardiovascular prognosis
• clinical trial

Acknowledgements

The authors gratefully acknowledge the REWIND study participants, the investigators, and study coordinators who cared for them. The authors thank Dr. Shirin Ghodke (Eli Lilly Services India Limited, Bangalore, India) for medical writing assistance.

Author contributions

G.F., J.M.M., L.R., and M.A.B, reviewed the literature and interpreted the data. S.R. P.R-M., and R.K. did or confirmed the statistical analyses and interpreted the data. C.A., L.S., and H.C.G. (REWIND Chair) interpreted the data. All authors critically reviewed and revised the draft and approved the report before submission. All authors agreed to be accountable for accuracy, integrity, and other aspects of the work.

Disclosure statement

This study was funded by Eli Lilly and Company. G.F., P.R-M., and R.K. report no conflicts of interest relevant to this article. L.R. reports grants from the Swedish Heart Lung Foundation, Region Stockholm, and Boehringer Ingelheim, fees for consulting, travel, and clinical research grant from Eli Lilly and Company, and fees for consulting and speaking from Boehringer Ingelheim, Novo Nordisk, Merck, and Bayer. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly and Company, AstraZeneca, Merck, Novo Nordisk, and Sanofi; honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, and Sanofi; and consulting fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck, Novo Nordisk, Janssen, Sanofi, Kowa. S.R. is an employee of Eli Lilly and Company. J.M.M., L.S., and M.A.B. are employees and stockholders of Eli Lilly and Company. C. A. was an employee of Eli Lilly and Company. No other potential conflicts of interest relevant to this article were reported.

Data availability statement

The data that support the findings will be disclosed only upon request and approval of the proposed use of the data by a review committee. All the data for the present report came from the Population Health Institute (PHRI) in Hamilton, Canada, who also did all the data analysis for the REWIND trial. The REWIND data sharing policy is described in the Supplemental Material.

Additional information

Funding

This work was sponsored by Eli Lilly and Company.