PracticeUpdate Cardiology Best of 2018

AHA 2018 27

Type 2 Diabetes Patients Receiving Empagliflozin Experience Left Ventricle Reverse Remodeling Changes were seen within 6 months, suggesting a fast-acting mechanism of action. T he SGLT2 inhibitor empagliflozin can initiate reverse remodeling and changes in left ventricular structure " …these results reinforce the guidelines that emphasize the importance of empagliflozin as a priority in patients with type 2 diabetes who have established cardiovascular disease. "

and function within 6 months, according to the results of the EMPA-HEART Cardiolink-6 study. To investigate how empagliflozin may improve cardiovascular health, as has been described in previous observational studies, the EMPA-HEART investigators randomized 97 patients with type 2 dia- betes and well-treated coronary artery disease with no history of heart failure to receive either empagliflozin (10 mg/day) or placebo. Patients received a baseline cardiac MRI, with repeat cardiac MRI eval- uation at 6 months. The primary study endpoint was change in left ventricular mass index at 6 months, which was significantly greater with empag- liflozin than with placebo (–2.5 g/m 2 vs –0.01 g/m 2 , P = .01). “Empagliflozin has an important effect that occurs within the short term to facil- itate clinically and statistically significant reductions in left ventricular mass,” study

and despite that, and despite the fact that most of the patients were well-treated with background therapy and had normal blood pressure, these results were quite compel- ling,” Dr. Verma said. Dr. Verma noted that he was impressed with how quickly empagliflozin was able to mediate a reverse remodeling effect, highlighting that he was “pleasantly sur- prised that there was significant reduction in the left ventricular mass index that was observed within 6 months.” “The curves in the EMPA-REG outcome trial appeared to separate very early after treatment was initiated,” Dr. Verma contin- ued. “Therefore, the benefit that is being observed in the large outcome trials sug- gested that we search for an important mechanism that may be occurring quickly. Most studies of reverse remodeling are done over the long term, and the fact that we are observing this within 6 months is quite intriguing.” Although these results chiefly elucidate an important mechanism of action for the car- dioprotective effects of SGLT2 inhibitors, Dr. Verma suggested that these findings do hold relevance for clinical practice in that they are consistent with current guide- line recommendations, going so far as to suggest that these results “reinforce the guidelines that emphasize the importance of empagliflozin as a priority in patients with type 2 diabetes who have established car- diovascular disease.” “The next question we would like to ask,” said Dr. Verma, “is whether these therapies can be beneficial even in people without diabetes.” Future studies may investigate such issues, as well as address limitations of the pres- ent study, such as its small sample size, relatively short follow up, and single-center design. This study was supported by an inves- tigator-initiated grant from Boehringer Ingelheim. www.practiceupdate.com/c/76130

presenter Subodh Verma, MD, of St. Michael’s Hospital in Toronto, Canada, told Elsevier’s PracticeUpdate . “Left ventricular mass is well recognized as a key surro- gate marker of cardiovascular death and all-cause mortality.” Notably, there were no significant differ- ences in secondary cardiac outcomes between patients receiving empagliflozin and those receiving placebo, including in left ventricular end-systolic volume index, left ventricular end-diastolic volume index, and left ventricular ejection fraction. Despite the limited scope of the results, Dr. Verma said he found them to be encouraging. “The vast majority of patients that we enrolled in the study had relatively nor- mal left ventricular mass to begin with,

© AHA/Todd Buchanan 2018

VOL. 3 • NO. 4 • 2018