Meta-analysis confirms benefits of SGLT2 inhibitors in various high-risk populations
Click Here to Manage Email Alerts
Key takeaways:
- SGLT2 inhibitors consistently reduce risk for death from heart disease and hospitalization for heart failure in various types of high-risk patients.
- Widespread adoption of SGLT2 inhibitors is needed.
SGLT2 inhibitors reduce risk for CV death and HF events in patients with any or multiple of HF, type 2 diabetes and chronic kidney disease, according to a meta-analysis published in the Journal of the American College of Cardiology.
The researchers conducted a meta-analysis of 13 trials of SGLT2 inhibitors vs. placebo in 90,413 patients with HF, type 2 diabetes and/or chronic kidney disease (CKD).
Image: Adobe Stock
“Type 2 diabetes, HF and CKD frequently overlap, but the effect of SGLT2 inhibitors in patients with varying multimorbidity remains less clear because the individual trials were underpowered to assess subpopulations,” Muhammad Shariq Usman, MD, research fellow and cardiovascular outcomes researcher at the University of Mississippi Medical Center, and colleagues wrote. “Accordingly, there are concerns that the benefits of SGLT2 inhibitors may be attenuated in the presence of multiple comorbidities. Furthermore, the effect of SGLT2 inhibitors on CV death remains unclear owing to inconsistent results across individual trials. Therefore, the aim of this systematic review and meta-analysis was to evaluate the effect of SGLT2 inhibitors on outcomes in subgroups of patients with varying combinations of CV, kidney and metabolic comorbidity.”
Risk reductions
Compared with placebo, SGLT2 inhibitors reduced risk for first incidence of CV death or HF hospitalization by 24% in patients with HF (HR = 0.76; 95% CI, 0.72-0.81), by 23% in patients with type 2 diabetes (HR = 0.77; 95% CI, 0.73-0.81) and by 23% in patients with CKD (HR = 0.77; 95% CI, 0.72-0.82), according to the researchers.
The benefit was consistent in patients with HF and reduced or preserved ejection fraction, in patients with HF with or without type 2 diabetes and in patients with HF with or without CKD, the researchers wrote.
The benefit was also consistent in patients with type 2 diabetes with or without CKD, in patients with type 2 diabetes without HF, in patients with CKD without HF and in patients with all three conditions, Usman and colleagues wrote.
Compared with placebo, SGLT2 inhibitors reduced risk for CV death by 16% in patients with HF, by 15% in patients with type 2 diabetes and by 12% in patients with CKD, according to the researchers.
“The present analyses provide comprehensive evidence that SGLT2 inhibitors improve HF outcomes in patients with HF, type 2 diabetes, CKD and any combination of these diseases, with a consistent but more modest benefit on CV death,” Usman and colleagues wrote. “These findings support a ‘call to action’ for the widespread adoption of the use of SGLT2 inhibitors across all three patient populations.”
SGLT2 inhibitors ‘should be widely embraced’
In a related editorial, Stephen D. Wiviott, MD, senior investigator and chairman of the clinical events committee with the TIMI Study Group, cardiovascular medicine specialist at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, and David D. Berg, MD, MPH, cardiologist at Brigham and Women’s Hospital and investigator in the TIMI Study Group, wrote that “with an adequate sample size (accomplished through rigorous meta-analysis), it is undeniable that SGLT2 inhibitors reduce the risk of cardiovascular death in patients with cardio-renal-metabolic disease. In other words, these are agents with the potential to prevent or modify the course of cardiovascular disease, including cardiovascular mortality, in multiple patient populations.
“The remarkable consistency in the effects of SGLT2 inhibitors on HF hospitalization (approximately 30% relative risk reduction), not just in the overall subgroups but in the subgroups with multiple comorbidities, highlights another key point, which is that there does not appear to be any meaningful effect modification by one’s individual comorbidity profile,” they wrote. “Simply stated, SGLT2 inhibitors are beneficial in diverse populations and should be widely embraced by clinicians caring for such patients.”
Reference:
Perspective
Back to Top
This analysis fills a gap that was not addressed by most of the randomized trials of SGLT2 inhibitor treatment for patients with HF: What are the outcomes for patients with comorbid disease? The data provided are more than reassuring. The benefits of the therapy extend to patients who might have been excluded from the original trials.
As with many cardiovascular trials, the patient populations studied included many fewer women and didn't represent the prevalence of disease in women.
Readers of this paper would do well to print the Central Illustration and display it in their clinic as a reminder of the benefits of SGLT2 inhibitors in nearly all patients with HF. There is no reason for therapeutic inertia in light of the evidence of benefit.
I hope that these findings will move the needle on the prescription of SGLT2 inhibitors, though the biggest barrier continues to be cost and lack of insurance coverage for these medications. High co-pays can really deter patients from accepting prescriptions, too.
Collapse
Click Here to Manage Email Alerts