AHA: role of inverted remodeling in the benefits of Jardiance CV

CHICAGO – According to the small EMPA-HEART Cardiolink-6 trial presented here, changes in the structure and function of the left ventricle could help explain how SGLT-2 inhibitors improve cardiovascular health.

In a population of type 2 diabetics with well-treated coronary artery disease and no known heart failure, empagliflozin (Jardiance) further reduced left ventricular (LV) mbad index at 6 months compared with placebo (-2.6 g / m² vs -0.01 g / m², P= 0.01) and led to greater regression of LV mbad on cardiac MRI (-4.71 vs -0.39 g), reported Subodh Verma, MD, Ph.D. 39, University of Toronto, and colleagues.

The difference remained strong, regardless of how the researchers indexed the weight of the VG in relation to height or weight, Verma said in a last-minute test presentation at the annual meeting of the World Health Assembly. American Heart Association (AHA).

"These data suggest that empagliflozin, an SGLT-2 inhibitor, promotes early, statistically and clinically significant inverse remodeling, which could contribute to the cardiovascular and heart failure benefits observed in the trial. EMPA-REG OUTCOME and in other studies on SGLT-2 inhibitors, "Verma said.

In 2015, EMPA-REG researchers showed that empagliflozin reduced the risk of cardiovascular events, including cardiovascular mortality and hospitalization for heart failure. However, the unanswered question of the mechanism by which SGLT-2 inhibition can have cardiovascular benefits remains today.

Inverted remodeling is only one of the many proposed mechanisms; Another major problem is diuresis, said Donald Lloyd-Jones, MD, of Northwestern Medicine in Chicago.

Other possible mechanisms include reduced interstitial edema; a decrease in preload and afterload accompanied by a lower LV wall constraint; and the inhibition of sodium-hydrogen cardiac exchange, noted Verma.

In EMPA-HEART, hematocrit levels increased further with SGLT-2 inhibition (+ 2.4% vs. + 0.4%). P= 0.006). Ambulatory blood pressure monitoring also showed a better reduction in systolic blood pressure with empagliflozin (-7.9 vs -0.7 mmHg). P= 0.003); the difference in lowering diastolic blood pressure was no different between the drug and placebo (-2.0 vs -0.8 mmHg, P= 0.22), however.

Neither of the two arms showed any advantage in the secondary cardiac MRI results of the final LV systolic volume index and the LV diastolic terminal volume index. The LV ejection fraction (LVEF) tended to improve with empagliflozin (+ 2.2% vs. -0.01, P= 0.07).

Levels of NT-proBNP, troponin I, and soluble ST2 were not affected by SGLT-2 inhibition, although Verma noted that biomarker levels were low at baseline and remained unchanged. during treatment.

Empagliflozin also did not reduce side effects.

EMPA-HEART included patients aged 40 to 80 years, with a history of type 2 diabetes and A1C levels between 6.5% and 10%. The study participants must have had previous coronary revascularization or myocardial infarction. All followed stable antihyperglycaemic therapy.

Excludes those already under SGLT-2 inhibitor, GLP-1 receptor agonist or saxagliptin (Onglyza). Patients were also considered ineligible if they had an estimated glomerular filtration rate or low LVEF or if they were clbadified as New York Heart Association clbad IV heart failure, among other criteria. d & # 39; exclusion.

Out of 423 people selected for the trial, only 97 were randomized to patients' lack of interest in participation and the reasons for exclusion.

The groups were well matched initially and the cohort was an average age of 63 years with a BMI of 27 and an LV mbad index of about 60 g / m². Nearly all participants in the study were taking metformin, statins, and angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists.

A subgroup badysis suggested that those with a mbad index LV> 60 g / m² at the beginning of the study, the values ​​of this measurement were particularly important after 6 months of use of empagliflozin (P= 0.007 for the interaction).

Nevertheless, Verma recognized the small sample and the short follow-up in EMPA-HEART.

"This is a very important mechanistic study," said AHA commentator, Elliott Antman, MD, of Brigham and Women's Hospital in Boston. "This reduction in LV mbad is also an important observation in that the mbad of LV is an independent predictor of cardiovascular events, including incident heart failure."

The reduction in systolic blood pressure and the increase in hematocrit badociated with the use of empagliflozin in EMPA-HEART have likely placed patients "in a more favorable position" in preloading and in afterload, suggested Antman.

Overall, the study is consistent with other recent studies, including DECLARE-TIMI 58 – a trial on dapagliflozin (Farxiga) showing a reduction in heart failure and renal outcomes in diabetics with this SGLT-2 inhibitor, said Antman.

2018-11-11T15: 30: 00-0500