A new dawn for the treatment of heart failure? - Comorbidites and humility
BRIGHAM AND WOMEN’S TRANSATLANTIC DIALOGUES ON CONTROVERSIES IN CONTEMPORARY CARDIOLOGYDec. 4, 2016
Marc A Pfeffer and Martin R Cowie chose to focus on comorbidities and humility, to address what we do not know and what we do not like to talk about. Firstly, Pfeffer discussed diabetes mellitus (DM). He noted that the main aim of treatment lowering HbA1c, is mostly based on epidemiological data. While evidence suggests a benefit of intensive glucose-lowering therapy on microvascular complications, generally no positive effect has been observed on CV disease and on mortality.
The diabetes field was stirred when a relationship between treatment with rosiglitazone and the risk of myocardial infarction (MI) and possibly death from CV causes was published.12 Pfeffer noted that this effect was, however, not seen in a randomised controlled trial. This publication led to the FDA (and similar EMA) requirement that new antidiabetic agents had to be tested for CV safety, by means of non-inferiority study designs in comparison with placebo. Unfortunately, the regulation does not include evaluation of the effect on HF, even though it is the major non-fatal end point as well as the main cause of death in diabetes trials.
Little attention was paid to the HF benefit seen with empagliflozin treatment in the EMPA-REG OUTCOME trial
The non-inferiority CV outcome trials evaluating DPP4- inhibitors, SAVOR-TIMI 53, EXAMINE and TECOS, all showed that they were not harming patients, but HF was not included in the primary endpoint. When rosiglitazone was evaluated in type 2 diabetes (T2DM) patients in the randomised RECORD trial, it turned out that it did not increase MI, as had been suggested by the epidemiological study.12 It did, however, increase the risk of HF.13 Several studies showed that T2DM patients were not harmed, but they were not helped much either.
Then came the EMPA-REG OUTCOME study in September 2015, showing that fewer people died and less heart failure was seen in those receiving treatment with empagliflozin.14 Still, little attention was given to this HF benefit, as exemplified by a vote of 12 yes vs. 11 no on the question whether the available data convinced the attendants of an FDA Endocrinologic and Metabolic Drugs Advisory Committee Meeting that empagliflozin reduces CV mortality in the population studied. Pfeffer therefore calls for more cross-boundary education, to increase awareness on the important link between T2DM and heart failure.
Marc A Pfeffer, MD – Victor J. Dzau Professor of Medicine Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA