No new danger for CV events with Farxiga in older adults

Issue: August 2015

BOSTON — Farxiga is not associated with an added risk for cardiovascular events in older adults with type 2 diabetes, cardiovascular disease and hypertension, according to study findings presented here.

In a post-hoc, pooled analysis of 19 studies involving older, high-risk adults with type 2 diabetes and a follow-up of approximately 4 years, researchers found that Farxiga (dapagliflozin, AstraZeneca) did not lead to an increase in major adverse cardiac events (MACE), CV death, myocardial infarction (MI) or stroke, while leading to reductions over time in HbA1c, body weight and blood pressure levels.

“Cardiovascular disease and hypertension are common co-morbidities in patients with type 2 diabetes, especially in older patients,” Ingrid Gause-Nilsson, MD, PhD, a research physician with AstraZeneca, told Endocrine Today. “It is important to evaluate that medications [used] to treat type 2 diabetes do not negatively affect the risk for these patients, as they already are at increased risk of having new cardiovascular events.”

Ingrid Gause-Nilsson

Gause-Nilsson and colleagues analyzed data from 1,263 adults aged 65 years or older (mean age, 70 years) with a history of CV disease and hypertension from eight short-term (12 to 24 weeks) and 11 short-term plus long-term studies (24 weeks plus; up to 4 years). Within the study participants, 707 participants were assigned dapagliflozin (in most cases, 10-mg doses; in some cases, 2.5 mg and 5-mg doses); 556 patients were assigned a comparator (in most cases, placebo; in some cases, placebo plus metformin). Baseline demographic characteristics were similar for both groups.

CV endpoints

Researchers used Cox proportional hazards stratified by study to measure MACE, MACE plus unstable angina, CV death, MI and stroke.

The hazard ratio for MACE was 0.92 (0.51, 1.64); for MACE plus unstable angina, the hazard ratio was 0.82 (0.5, 1.37). For CV death, the hazard ratio was 1.02 (0.37, 2.81); for MI, the hazard ratio was 0.77 (0.30, 1.99); for stroke, the hazard ratio was 0.81 (0.32, 2.05).

Patients assigned dapagliflozin showed a decrease in HbA1c over time, with an adjusted mean difference at week 24 of -0.37%, as well as a decrease in body weight, with an adjusted mean difference at 24 weeks of -2 kg.

Adverse events

Researchers also noted adverse events of special interest over the course of treatment, including genital and urinary tract infections, which occurred in a greater proportion of patients assigned dapagliflozin vs. comparators. Renal impairment and renal failure, mainly based on pre-specified, laboratory-based criteria, were also seen more frequently in patients assigned dapagliflozin. Researchers observed no increased risk for hypoglycemia.

Results were consistent with a previous pooled meta-analysis of 21 trials involving adults with type 2 diabetes followed for up to 4 years, which showed no increase in MACE or MACE plus unstable angina for those assigned dapagliflozin (n=5,936) vs. comparators (n=3,403). The hazard ratio for MACE was 0.77; the hazard ratio for MACE plus unstable angina was 0.79.

The results do not have any immediate clinical implications, Gause-Nilsson said, but add to the knowledge of dapagliflozin treatment in older adults.

“As previously reported, a meta-analysis of the dapagliflozin development program did not indicate any increased risk of cardiovascular events overall or in patients with some specific risk factors for cardiovascular disease,” Gause-Nilsson said. “The current post hoc analysis showed that this was true also for elderly patients, aged 65 years and older, with pre-existing cardiovascular disease and hypertension.”

The impact of dapagliflozin on CV risk is being prospectively tested in the ongoing DECLARE-TIMI 58 CV outcome study. Researchers with that trial aim to enroll 17,150 participants age 40 years or older with type 2 diabetes and an established risk of CVD or multiple risk factors. – by Regina Schaffer

Reference:

Gause-Nilsson IA, et al. Abstract 15-OR. Presented at: American Diabetes Association’s 75th Scientific Sessions; June 5-9, 2015; Boston.

Disclosure: All study authors report that they are employees of AstraZeneca.