Neuherberg, Germany—Severe hypoglycemic events are known to increase risk of cardiovascular (CV) events. What is less understood, according to a new study, is that a history of CV events can increase the likelihood of suffering severe hypoglycemia.

An article in Diabetes Care discusses the bidirectional association between severe hypoglycemic events (SHEs) and CV event risk and describes which patients are most likely to be at dual risk.

The international study group conducted a post hoc analysis of 14,752 Exenatide Study of Cardiovascular Event Lowering participants, Researchers focused on time-dependent associations between SHEs and subsequent major adverse cardiac events, including CV death, nonfatal myocardial infarction [MI] or stroke, fatal/nonfatal MI, fatal/nonfatal stroke, hospitalization for acute coronary syndrome (hACS), hospitalization for heart failure (hHF), and all-cause mortality (ACM). They also sought to identify any time-dependent associations between nonfatal CV events and subsequent SHEs.

The authors point out that severe hypoglycemia was uncommon and not associated with once-weekly exenatide therapy (hazard ratio 1.13 [95% CI, 0.94–1.36], P = .179).

In fully adjusted models, however, SHEs were shown to be associated with an increased risk of subsequent ACM (1.83 [1.38-2.42], P < .001), CV death (1.60 [1.11-2.30], P = .012), and hHF (2.09 [1.37-3.17], P = 0.001), while nonfatal MI (2.02 [1.35-3.01], P = .001), nonfatal stroke (2.30 [1.25-4.23], P = .007), hACS (2.00 [1.39-2.90], P <0.001), and hHF (3.24 [1.98-5.30], P <.001) were all associated with a subsequent increased risk of SHEs, according to the report.

“The elevated bidirectional time-dependent hazards linking SHEs and a composite of all CV events were approximately constant over time, with those individuals at dual risk showing higher comorbidity scores compared with those without,” the authors explain.

The study reached the conclusion that both a greater risk of SHEs after CV events as well as greater risk of CV events after SHEs validate a bidirectional relationship between CV events and SHEs in patients with high comorbidity scores.

Background information in the report notes, “In the post-2008 era of cardiovascular outcome trials (CVOTs) mandated by the U.S. Food and Drug Administration (FDA) for any new glucose-lowering drug, severe hypoglycemic events requiring third-party assistance have remained a major challenge complicating diabetes therapy. Post hoc analyses of several CVOTs have found that SHEs are associated with an increased risk of subsequent cardiovascular (CV) and all-cause mortality (ACM) events.”

The authors emphasize that patients with features of “frailty,” i.e., those with a high summary comorbidity score, are at the highest risk.

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