Medical Technology

Inhibitors of SGLT2 improve cardiovascular outcomes in all groups

Sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrate “remarkable consistency of class benefit” in enhancing cardiovascular outcomes for high-risk individuals across sex, age, and race/ethnicity categories.

The results of an analysis of a meta-analysis of 10 important random clinical trials were published online on January 5, in JAMA Open by Mukul Bhatrai, MD, a cardiology fellow at Southern Illinois University School of Medicine, Springfield (Illinois) and his colleagues.

“Our meta-analysis assessed a broad range of outcomes for efficacy in addition to defining the primary outcome in various subgroups of large clinical trials. It demonstrates that SGLT2 inhibitions are a highly effective class of drugs that can improve cardiovascular morbidity, mortality, and reduce hospitalization due to heart failure] in certain patients.” Bhattarai et al. write.

The cardiovascular outcomes of SGLT2 inhibitor treatment, they say, “can be compared across all trials, and it shows remarkable consistency of class benefit, despite the variances in the populations that are that are enrolled.”

They also observed that SGLT inhibitors did not reduce the risk of AMI overall and that most trials were short-term with a mean follow up of only 2.3 year.

Ten Trials, Consistent Cardiovascular Benefits

Bhattarai and his colleagues scoured the literature between January 10, 2021 until presentation at the meeting and other sources. They identified 10 placebo-controlled randomized clinical trials in which participants were diagnosed with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk factors diabetes, heart failure. In total, 71,553 high-risk patients received an SGLT2 inhibitor, while 32,500 received a placebo.

The primary outcome of cardiovascular disease or hospitalization for heart attack was observed in 8.10 percent of patients that were randomized to SGLT2 inhibitions, compared with 11.56% from the placebo group. This is a significant distinction with an odds ratio 0.67 ( .001). Both outcomes were lower in SGLT2 inhibitors as was the number of patients required to treat of 5.7 ( .001).

Patients taking SGLT2 inhibitors had significantly lower rates of major adverse cardiovascular events, defined as death due to cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke. The events occurred in 9.82 percent versus 10.22%, with an odds ratio of 0.90 ( P = .03).

Hospitalizations and emergency room visits with heart failure were also reduced with SGLT2 inhibitors (4.37 percent and 6.81 percent odds ratio, 0.67; P > .001) as was cardiovascular death (4.65% vs 5.14 percent odds ratio, 0.87; P = .009). According to the authors, heart failure could be reduced by a combination of a decreased interstitial fluid and an natriuretic action, and also by reducing heart fibrisis.

On contrary there were no reductions in acute myocardial ischemia, assessed in five of the studies. The event was observed in 4.66 percent of those who were taking SGLT2 inhibitors, compared with 4.70 percent in the placebo group. This is a non-significant difference with an odds ratio of 0.95 ( p = 0.22). This is probably due to the fact that SGLT2 inhibitors do not have antianginal properties or vasodilatory effects. they don’t decrease the amount of oxygen consumed by myocardium, and they don’t prevent the development of cardiac muscle, they note.

All-cause mortality was significantly lower in patients taking SGLT2 inhibitors, though they were at 7.09 percent versus 7.86% (odds ratio, 0.87; P = .004).

Benefits seen across age, Sex, and Race/Ethnicity Subgroups

Despite no difference in benefit between men and women compared to the placebo groups, the rates of heart failure hospitalizations or deaths due to cardiovascular disease were slightly higher for men than women (9.01 percent [odds ratio, 0.75] and. 5.34% [0.78]; P =.002]).

As we the time you reach age, SGLT2 inhibitors have benefited people who were younger than 65 years and those aged 65 years and over, though the primary outcome was slightly less in the younger group (6.94% [0.79; P < 0.001] vs 10.47 percent [0.78; P < .001]).

By race, the same advantages from SGLT2 inhibitors were seen among people who were White as compared to those who were Asian, Black, or of other race/ethnicity, with events rates of 8.77 percent (0.82; P < .001) and 8.75% (0.66; P = .06) respectively.

“Owing to the short-term duration of trials the future prospective studies with a long-term duration and post-marketing surveillance studies are warranted to discover the rate of cardiovascular outcomes,” Bhattarai and colleagues conclude.

The authors haven’t disclosed any information.

JAMA Netw Open. Published online January 5, 2021. Full Text

Miriam E. Tucker, freelance journalist, lives in Washington DC. She is a regular contributor to Medscape as well as other work appearing in the Washington Post, NPR’s Shots blog and Diabetes Forecast magazine. She is on Twitter @MiriamETucker.

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