- The cardiovascular benefits of AstraZeneca's Type 2 diabetes drug Farxiga appear more pronounced in patients with heart failure and a condition known as reduced ejection fraction, new findings reported Monday at the American College of Cardiology's annual meeting suggest.
- Farxiga, one of a class of drugs known as SGLT-2 inhibitors, reduced the risk of hospitalization for heart failure regardless of heart failure status or ejection fraction, a measure of how effectively the heart can pump blood. But only those patients with reduced ejection fraction experienced lower rates of cardiovascular death and death from all causes, according to sub-analyses of a study called DECLARE-TIMI 58.
- "The objective of this study was not really in heart failure and the number of patients with reduced ejection fraction is relatively small," cautioned Valentin Fuster, physician-in-chief at Mount Sinai Hospital, in a ACC press conference on the data Monday. "I would call this preliminary data," he added, while noting he viewed the results positively.
The new data from DECLARE-TIMI 58 are the first to categorize the benefit of Farxiga (dapagliflozin) by ejection fraction, giving cardiologists assembled at the ACC annual meeting in New Orleans a fuller picture of the SGLT-2 inhibitor's heart benefits.
"I think this is definitely a step forward in this class of medications," said Gurusher Panjrath, an associate professor of medicine at the George Washington University School of Medicine and chair of the ACC Heart Failure Council, in an interview. "Beyond overall cardiovascular benefit, sub-typing into the heart failure with reduced ejection fraction patients is a big plus."
Panjrath noted, though, that more data from other ongoing studies would help clarify the implications from the sub-analyses in DECLARE-TIMI 58.
Diabetes is considered a risk factor for heart failure, and proving the cardiovascular benefit of drugs like Farxiga has become an essential step for drugmakers looking to compete in the crowded therapeutic space.
Last year, AstraZeneca revealed that Farxiga met one of two primary endpoints in DECLARE TIMI-58, reducing the risk of cardiovascular death or hospitalization for heart failure. Yet the drug didn't significantly reduce the risk of major adverse cardiovascular events, or MACE, compared to placebo.
Monday's results expanded on that result, showing Farxiga's benefit to be greater in those with reduced left ventricular ejection fraction, defined in the study as less than 45%.
All patients experienced a reduced risk of hospitalization for heart failure. But in those with lower ejection fraction, the risk reduction extended to cardiovascular death and all-cause mortality as well.
Additionally, among patients who had a previous heart attack, Farxiga reduced the risk of MACE by 16% compared to placebo.
Farxiga showed greater heart benefits in patients with reduced ejection fraction
|Among patients with reduced ejection fraction (vs. placebo)||Among patients without reduced ejection fraction (vs. placebo)|
|Hospitalization for heart failure (HHF) or CV death||38% relative risk reduction||12% relative risk reduction|
|HHF alone||36% relative risk reduction||24% relative risk reduction|
|CV death alone||45% relative risk reduction||No benefit observed|
|All cause mortality||41% relative risk reduction||No benefit observed|
SOURCE: Presentation by Eri T. Kato, ACC
"The clinical implication of this finding is that ejection fraction is a strong tool to identify those who are at highest risk and may derive particular benefit from SGLT2 inhibitors," said Eri Kato, the study's lead author and a cardiologist at Kyoto University Hospital, in a statement from ACC.
Only 30% of the more than 17,000 patients enrolled in DECLARE-TIMI 58 had documented ejection fraction at the beginning of the study. Of those roughly 5,000 trial participants, 13% had heart failure with reduced ejection fraction.
The benefit of SGLT-2 inhibitors in heart failure has gradually become clearer since Eli Lilly's EMPA-REG study of Jardiance (empagliflozin) read out positively in 2015 — progress that Subodh Verma of St. Michael's Hospital at the University of Toronto dubbed "a serendipitous story" in an article published Monday in the journal Circulation.
Data from DECLARE-TIMI 58, as well as a similar trial sponsored by Johnson & Johnson, have bolstered confidence in use of SGLT-2 inhibitors more broadly. On Monday, ACC and the American Heart Association for the first time recommended use of the drug class in joint guidelines for the primary prevention of cardiovascular disease among Type 2 diabetes patients.
Trial results like those from DECLARE-TIMI 58 should spur more physicians to use SGLT-2 inhibitors earlier in treatment, said Rod Wooten, a vice president in AstraZeneca's cardiovascular and metabolic diseases unit, in an interview. "Physicians will have to look beyond glycemic control and look at cardiovascular risk more."
The Food and Drug Administration has accepted AstraZeneca's application to add cardiovascular data to Farxiga's label, and the company anticipates an expanded approval by the end of the year, Wooten said.
An additional OK, if forthcoming, could help AstraZeneca compete against Eli Lilly and J&J. Prescription data from mid-February cited by Cowen & Co. show Jardiance holding a roughly 50% share of weekly new prescriptions, compared to about 26% for Farxiga and 18% for J&J's Invokana (canagliflozin).