CHICAGO – Dapagliflozin ( Farxiga / Forxiga AstraZeneca) showed an insignificant trend towards a reduced rate of major negative heart…
CHICAGO – Dapagliflozin ( Farxiga / Forxiga AstraZeneca) showed an insignificant trend towards a reduced rate of major negative heart failure (MACE) but significantly reduced hospitalization for heart failure in the DECLARE-TIMI 58 trial in patients with type 2 diabetes.
The trial was presented here at the Scientific Sessions of the American Heart Association (AHA) 2018 by Chief Writer Stephen Wiviott, MD, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. It was simultaneously published online in the New England Journal of Medicine .
“ What we see in this experiment is a similar theme for other major attempts with sodium glucose cotransporter-2 (SGLT2) inhibitors ̵
1; a significant reduction in heart failure hospitalization and kidney disease,” Wiviott commented theheart.org | Medscape Cardiology.
However, DECLARE-TIMI 58 differs from the other trials by recording a much wider and healthier population including 10,000 patients without existing cardiovascular disease but with multiple risk factors, as well as 7,000 patients with the present cardiovascular disease. “
” We found that the benefit of dapagliflozin on heart failure was similar in those with and without existing cardiovascular disease, whereas the effect on MACE differs between these populations without any effect in the primary prevention group and a trend towards a reduction of those with secondary prevention.
“All three SGLT2 inhabitants studies have found a major effect on the heart failure endpoint, and our attempt adds the known literature in that regard. But it also extends this heart failure to the primary preventive diabetic population, “said Wiviott.
He added: “If we look at all experiments empagliflozin showed the most benefit of MACE, but it was still less than heart failure. I think after the DECLARE-TIMI 58 test we can now say that the biggest advantage of The SGLT2 inhibitors are to prevent heart failure and the reduction of cardiac cardiovascular disease is limited to patients with existing underlying cardiovascular disease. “
” The DECLARE TIMI-58 test also provides very calming data on safety without evidence of stroke, amputations or bladder cancer, “he added.
The major cardiovascular outcomes of newer type 2 diabetes drugs are performed to demonstrate safety following a mandate by the US Food and Drug Administration (FDA) 2008 after concerns about CV injury with older Type 2 diabetes drugs.
But so far none of the eight completed CV outcomes have identified excess CV risk from the current drugs, and three have actually shown an advantage.
These included two studies of oral SGLT2 inhibitors: EMPA-REG OUTCOMES experiment with empagliflozin ( Jard iance Boehringer Ingelheim / Lilly) and CANVAS with canagliflozin ( Invokana Janssen). In both studies, all patients had type 2 diabetes and existing CVD or had a high risk of CVD.
Similarly, in the third study, LEADER, with the injectable glucagon-like protein 1 (GLP-1) agonist liraglutide ( Victoza Novo Nordisk), all patients with type 2 diabetes had established CV disease (CVD) or chronic renal failure or at least 60 years of age with CVD risk factors.
DECLARE now adds this list of studies showing cardiovascular disease with new diabetes drugs, although the benefits are limited to the endpoint of the heart failure and did not show the same reductions in MACE as the other SGLT2 inhibitor or LEADER. However, this trial submitted a low-risk population of type 2 diabetes patients than in previous studies of cardiovascular studies.
For the DECLARE-TIMI 58 study, 17,160 patients with type 2 diabetes who had atherosclerotic CVD or multiple risk factors for CVD were randomly assigned to dapagliflozin 10 mg daily or placebo in addition to standard therapy.
The primary safety result was a composite of MACE events, defined as CV death, myocardial infarction (MI) or ischemic stroke. The two co-effective endpoints were MACE and a composite of cardiovascular death or hospitalization for heart failure.
Following an average follow-up of 4.2 years, the primary safety result met the criteria for non-inferiority.
With respect to the two efficacy results, MACE was numerically reduced in the dapagliflozin group, but this result was not significant. CV death / heart failure hospitalization endpoint was significantly reduced. This was a consequence of a lower hospital stay for heart failure.
A key rat outcome was a renal composite (≥40% decrease in the calculated glomerular filtration rate to <60 ml / min per 1.73 m 2 of the body surface area, renal kidney disease or death from renal or CV- causes). This was also significantly reduced with dapagliflozin.
|Table 1. DECLARE-TIMI 58: Main Result |
After the groups were separated in patients with and those who had no established cardiovascular disease, MACE was not significantly reduced by dapagliflozin in those with established disease but there was no effect in the non-established CVD.