Influence of sex, age and race on coronary and heart failure events in patients with diabetes and post-acute coronary syndrome

Abstract

Background

Women, older patients and non-White ethnic groups experience a substantial proportion of acute coronary syndromes (ACS), although they have been historically underrepresented in ACS randomized clinical trials (RCTs). To assess the influence of sex, age and race on major adverse cardiovascular events (MACE) and on heart failure events, we studied patients with type 2 diabetes in a large post-ACS trial (EXAMINE).

Methods

Differences in baseline characteristics and the respective composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE) and cardiovascular death or heart failure hospitalization (HF events) were evaluated by subgroups in a cohort of post-ACS patients with diabetes, using unadjusted and adjusted Cox regression modelling.

Results

The EXAMINE trial enrolled 5380 patients with 35% aged > 65, 32% female and 27% non-White. The risk of MACE was higher in non-White compared to White patients after adjustment for potential confounding (HR = 1.35; 95% CI 1.04–1.75), but there were no significant differences by sex and age (HR = 1.03; 95% CI 0.87–1.22 for women; HR = 1.14; 95% CI 0.96–1.35 for patients ≥ 65 years). The risk of HF events was higher in non-White patients (HR = 1.56; 95% CI 1.13–2.14), and in patients aged > 65 (HR = 1.33; 95% CI 1.07–1.66) and nominally so in women (HR = 1.23; 95% CI 0.99–1.52). The additive risk of each demographic factor (women, older age and non-White race) was greater for HF events in comparison with MACE. Moreover, non-White elderly patients consistently had poorer prognosis regardless of sex.

Conclusions

Older adults, women and non-White patients with diabetes who are post-ACS are often underrepresented in RCTs. The risk for HF events was higher in older and non-White patients, with a trend towards significance in women, whereas only non-White patients (and not women and older patients) were at higher risk for MACE. Future trials should enrich enrollment of these persons at risk.

Graphic abstract

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Acknowledgements

The EXAMINE trial was funded by Takeda.

Funding

The EXAMINE trial was funded by Takeda.

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Corresponding author

Correspondence to Faiez Zannad.

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Conflict of interest

XR, JPF, FC, ZL and CM have nothing to disclose. AS has received support from the FRSQ-Junior 1 clinician scientist award, the Alberta Innovates Health Solution Clinician Scientist fellowship, the European Society of Cardiology Young Investigator research grant, and has received support from Roche Diagnostics, Astrazeneca, Boeringer-Ingelheim, Novartis, Servier, Novo-Nordisk, and the Canadian Cardiovascular Society Bayer Vascular award. Dr Ferreira has received consulting fees from Boehringer-Ingelheim. GB reports other from Merck, Novo Nordisk, Vasular Dynamics, Bayer, Ionis, Alnylam, KBP Biosciences, outside the submitted work. CPC reports in calendar years 2018–2020: (1) Research Grants from: Amgen, Boehringer-Ingelheim (BI), Bristol-Myers Squibb (BMS), Daiichi Sankyo, Janssen, Merck, Novo Nordisk, Pfizer, and (2) Consulting fees from Aegerion, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, BI, BMS, Corvidia, Eli Lilly, HLS Therapeutics, Innovent, Janssen, Kowa, Merck, Pfizer, Rhoshan, Sanofi. WBW reports personal fees from Takeda Millenium Pharmaceuticals, outside the submitted work. FZ reports steering committee personal fees from Applied Therapeutics, Amgen, Bayer, Boehringer, Novartis, Janssen, Cellprothera and CVRx, advisory board personal fees from, AstraZeneca, Vifor Fresenius, Cardior, Cereno pharmaceutical, Corvidia, Merck, Myokardia, NovoNordisk and Owkin, stock options at Cereno and G3Pharmaceutical, and being the founder of the Global Cardiovascular Clinical Trialist Forum.

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The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki.

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Informed consents were obtained from each patient.

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All authors agree with de publications of the present article.

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Rossello, X., Ferreira, J.P., Caimari, F. et al. Influence of sex, age and race on coronary and heart failure events in patients with diabetes and post-acute coronary syndrome. Clin Res Cardiol (2021). https://doi.org/10.1007/s00392-021-01859-2

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Keywords

  • Type 2 diabetes mellitus
  • Acute coronary syndromes
  • cardiovascular outcomes
  • Heart failure
  • Randomized clinical trials