Clinical trial failings leave effect of diabetes medications on HF uncertain
medwireNews: Heart failure (HF) is poorly characterized and reported even in cardiovascular (CV) outcome trials of glucose-lowering therapies, making it difficult to ascertain the effect of antidiabetic medications on this outcome, say the authors of a systematic review.
“Even recently completed large CV outcome trials of novel glucose lowering agents lack sufficient details to fully appraise treatment effects on a HF endpoint or relative safety in patients with prevalent HF,” they write in the Journal of the American College of Cardiology.
The team found that baseline HF prevalence was reported in just 67% of 21 phase III or IV randomized clinical trials (involving 152,737 patients), although it was reported in all those published after 2010.
Prevalence ranged from 0.5% to 27.9%, but only one trial provided a definition of HF, and information relating to ejection fraction, functional class, and treatment was sparse and inconsistent.
Of the 20 trials with published results, only 30% reported incident HF during follow-up (which ranged from 1.7 to 17.9%). Among those that did, the definitions varied or were not published and it was rarely clear whether events were adjudicated.
Javed Butler (Stony Brook Medicine Health Sciences Center, New York, USA) and study co-authors describe better characterization and reporting of HF in these trials as an “unmet and compelling need.”
They point out that the prevalence of HF is “poised to increase” and that its presence may have a substantial impact on the risk profiles of diabetes patients and could influence the CV benefits of glucose-lowering therapies.
This is particularly notable considering that the CV safety trials for glucose-lowering therapies have actually led to efficacy indications within the glucagon-like peptide-1 receptor agonist and sodium-glucose cotransporter-2 inhibitor classes, they add.
“As such, subgroup analysis by presence or absence of baseline HF should be standard and adequate enrollment of both subgroups should be ensured to allow for meaningful analysis” within the CV outcome trials, write Butler et al, although they stress that dedicated trials will be needed to support drug labeling and guideline changes.
They lay out detailed recommendations for trial population enrolment, data collection, standardized endpoint event ascertainment, and endpoint event adjudication.
The team also presented the findings today at the American College of Cardiology scientific sessions in Orlando, Florida, USA.
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