Summary | Real world evidence and outcomes in the management of heart failure patients with T2DM

Prof. Lam started by presenting a global picture of the burden of HF. She highlighted the high prevalence of HF in Asia. In Southeast Asia there are an estimated 9 million HF cases. The global burden of diabetes is even worse. Lam said that Asia is the capital of diabetes in the world: 60% of all diabetes patient live in Asia and the number of patients in Southeast Asia is expected to increase by 70% by 2035.

The Asian-HF registry prospectively follows HF patients from 11 regions in Asia [29]. Lam showed that there are interactions between regional income level and ethnicity on risk factor burden in HFrEF [30]. For instance, among those of Indian ethnicity, the odds of having diabetes in HF patients from a high income region (like Singapore) was >5 times higher compared to HF patients from a low income region (like India). She suggested that this might be explained by the rapid demographic transitions that some countries have experienced. She gave the example of Singapore; a fishing village in the 1960s and a metropolis today. A rapid transition from starvation to diets rich in carbohydrates might explain the high incidence of diabetes and HF nowadays.

Comparing registry data from Asian HF patients with Swedish HF patients showed that more Asian HF patients had diabetes, for each HF type [31]. As BMI increased, prevalence of diabetes increased for both Asian and Swedish HF patients, but at any given BMI, diabetes prevalence was much higher in Asian patients, even at BMI <20 kg/m². Clustering of comorbidities in the Asian-HF register by a machine learning approach resulted in five phenotypes: 1) young, familial HFrEF, 2) traditional, ischemic HFrEF, 3) elderly, atrial fibrillation (AF)-type HFpEF, 4) metabolic phenotype HFpEF, 5) lean diabetic HFpEF [32].

Subanalyses of data from the Asian-HF registry suggested that in those with a low BMI, women were more likely to develop diabetes than men, and in women diabetes was more related to CKD [33]. Also, LV geometry and diabetes were more strongly related in women than in men, and diabetes was associated with worse outcomes after 1 year in women compared to men.

Real world practices of treatment of patient with diabetes and HFrEF using data from the Asian-HF registry showed that patients with diabetes were less likely to be prescribed guideline-directed medical therapies for HF (RAASi and mineralocorticoid receptor antagonists [MRAs]). Use of diabetes medication in HF patients varied widely throughout Asia; the most commonly used therapy was metformin, followed by sulfonylurea (SU), then insulin and dipeptidyl peptidase 4 (DPP-4) inhibitors and some patients were on thiazolidine (TZD). Use of TZD in the presence of HF is contra-indicated according to the 2016 ESC HF guidelines, because it can exacerbate HF. Diabetes worsens outcomes in HF patients, and only metformin was associated with a reduced risk of the composite outcome of HF hospitalization and death [34]. Lam noted that this was an observational study and although adjustments for baseline characteristics were done, it was not an RCT. Nevertheless, the results are reassuring because the ESC HF guidelines of 2016 recommend metformin as first-line therapy for glycemic control in patients with HF and diabetes. Comparing data from the Asian-HF registry with data from the ACC-Diabetes collaborative registry showed that HF patients from the US were more likely to be prescribed insulin than Asian HF patients, US patients were less likely to be prescribed SUs and a small percentage was prescribed TZD [35]. Use of guideline-directed medical therapies for HF was lower in patients from lower income Asian countries. Both in the US and Asia there are opportunities to improve evidence-based therapy for diabetes and HF.

Observational real-world data from the CVD REAL 2 study, which includes T2DM patients from Asia, showed that use of SGLT2i was associated with reduced risk for HF hospitalization and the composite of death and HF hospitalization [36]. Inspired by these results, the ADOPT (Asian Diabetes Outcomes Prevention trial) is about to be launched, in which T2DM patients with high risk for HF, indicated by NT-proBNP level >125 pg/mL, will be treated with intensive therapeutic regime, including RAASi and SGLT2i, or standard care and followed for the primary endpoint of CV outcomes.

References

Faculty

This is a summary of the presentation given by prof. Carolyn Lam, during the PACE symposium entitled 'Heart Failure, diabetes and SGLT2i: Time to change practice?', held during ESC HF in Athens, Greece on May 25, 2019.

View the slides of her presentation Watch the video of her presentation