JACC. Heart failure
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JACC. Heart failure · Jun 2018
ReviewWorsening Heart Failure During the Use of DPP-4 Inhibitors: Pathophysiological Mechanisms, Clinical Risks, and Potential Influence of Concomitant Antidiabetic Medications.
Although dipeptidyl peptidase (DPP)-4 inhibitors have been reported to have a neutral effect on thromboembolic vaso-occlusive events in large-scale trials, they act to potentiate several endogenous peptides that can exert deleterious cardiovascular effects. Experimentally, DPP-4 inhibitors may augment the ability of glucagon-like peptide-1 to stimulate cyclic adenosine monophosphate in cardiomyocytes, and potentiation of the effects of stromal cell-derived factor-1 by DPP-4 inhibitors may aggravate cardiac fibrosis. These potentially deleterious actions of DPP-4 inhibitors might not become clinically apparent if these drugs were to promote sodium excretion. ⋯ The only trial that specifically evaluated patients with pre-existing left ventricular dysfunction observed important drug-related adverse structural and clinical effects. In conclusion, an increased risk of worsening heart failure appears to be a class effect of DPP-4 inhibitors, even in patients without a history of heart failure. Additional clinical trials are urgently needed to elucidate the benefits and risks of DPP-4 inhibitors in patients with established left ventricular dysfunction.