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EXAMINE: Use of Nesina, placebo with, without ACE inhibitors reveals similar CV outcomes
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BOSTON — The use of Nesina compared with placebo with and without ACE inhibitors did not result in any significant differences in cardiovascular outcomes, cardiac ischemic events and cardiovascular hospitalizations in patients with type 2 diabetes and acute coronary syndrome, according to two study results of the EXAMINE trial.
“The original objective of the EXAMINE trial was to demonstrate the major CV event rates [of] ... alogliptin vs. placebo and [the rates] were found to [be] noninferior on alogliptin vs. placebo in patients receiving the standard of care for type 2 diabetes and recent acute coronary syndrome,” William B. White, MD, of the University of Connecticut, said during a presentation here.
William B. White
White and colleagues evaluated 5,380 patients from the EXAMINE trial who were randomly assigned to receive Nesina (alogliptin, Takeda Pharmaceuticals USA, Inc.) or placebo added to existing anti-hyperglycemic and CV therapies to determine CV outcomes after treatment.
Sixty-two percent of participants were using an angiotensin-converting enzyme (ACE) inhibitor (1,681 on alogliptin; 1,642 on placebo).
Rate of adverse events
Similar rates of nonfatal myocardial infarction (MI) and stroke were found between the alogliptin and placebo with ACE inhibition (HR = 0.97; 95% CI, 0.79-1.19) and without ACE-inhibition use (HR = 0.94; 95% CI, 0.73-1.21). More participants assigned placebo (7.2%) compared with alopliptin (6.8%) experienced CV death or hospitalized heart failure than those on ACE inhibitors at baseline (HR = 0.93; 95% CI, 0.72-1.2). No effect on hospitalized heart failure alone in patients treated with ACE inhibitors was found between alogliptin or placebo (HR = 1.07; 95% CI, 0.73-1.56). Similarly, no impact on CV events were found between higher and lower doses of ACE inhibitors.
Pre-randomization for heart failure history and ACE-inhibitor use at baseline revealed nonfatal MI and stroke occurred in more patients assigned placebo (16.5%) compared with alogliptin (13.9%; HR = 0.87; 95% CI, 0.63-1.19). Hospitalized heart failure and CV death also occurred more in patients assigned placebo (13.2%) compared with alogliptin (12%; HR = 1.02; 95% CI, 0.72-1.44).
“These data do not support an unfavorable interaction with ACE inhibitor use and therapy with alogliptin in [high-risk] CV patients,” White said.
Additional evaluation of patients
In a separate study, Yuichi J. Shimada, MD, of The Harvard Clinical and Translational Science Center, and colleagues evaluated the same patients from the EXAMINE trial to determine the rates of cardiac ischemic events and CV hospitalizations among this population.
Patients were randomly assigned to placebo (n = 2,679) or alogliptin (n = 2,701).
The researchers found that event rates were generally high among all of the study’s participants, not only for CV hospitalizations (HR = 1.02; 95% CI, 0.89-1.17) but also for coronary revascularizations (HR = 0.98; 95% CI, 0.82-1.16). However, no significant differences in any of the cardiac ischemic endpoints were found between the two groups.
“These new data demonstrate that alogliptin did not increase the rates of cardiac ischemic events or CV hospitalizations in a high-risk post-acute coronary syndrome patient population,” Shimada concluded. “In addition, since CV hospitalization and revascularization are a main driver of health care costs, these data suggest that there would be no adverse impact on health care resource utilization and costs.” – by Amber Cox
References :
Shimada YJ, et al. Abstract 13-OR.
White WB, et al. Abstract 12-OR.
Presented at: American Diabetes Association’s 75th Scientific Sessions; June 5-9, 2015; Boston.
Disclosure s : White reports various financial ties with Ardea Biosciences, AstraZeneca Pharmaceuticals LP, Forest Research Institute, Roche USA, Takeda Pharmaceutical Company Limited and Teva Pharmaceuticals USA. Shimada reports no relevant financial disclosures.
Perspective
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Anthony L. McCall, MD, PhD
DPP-IV inhibitors are popular, oral incretin drugs with moderate glucose lowering efficacy and good tolerability in type 2 diabetes. Post-marketing safety studies like EXAMINE had new data presented about safety regarding risks known to be increased in people with type 2 diabetes.
White presented a thorough analysis of heart failure risk in patients from the EXAMINE trial showing no evidence of increased risk with the DPP-IV inhibitor alogliptin, whether patients were on ACE inhibitor therapy or not. The data raised no concerns for increase in heart failure. The issue of heart failure hospitalization has been specifically a concern for this class of drugs, and there is a "neutral" result, with reassurance that safety issues are not found about CV outcomes and specifically risk of congestive heart failure that is known to be more common in type 2 diabetes. These are important new observations on safety.
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