Confirming the bidirectional nature of the association betwe
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This study sought to confirm a bidirectional association between severe hypoglycemic events (SHEs) and cardiovascular (CV) event risk and to characterize individuals at dual risk.

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 (SHEs) 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.

In this post hoc analysis of 14,752 Exenatide Study of Cardiovascular Event Lowering (EXSCEL) participants, we examined time-dependent associations between SHEs and subsequent major adverse cardiac events (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), as well as time-dependent associations between nonfatal CV events and subsequent SHEs.

RESULTS: SHEs were uncommon and not associated with once-weekly exenatide therapy. In fully adjusted models, SHEs were associated with an increased risk of subsequent ACM, while nonfatal MI, nonfatal stroke, hACS and hHF were all associated with a subsequent increased risk of SHEs. 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.

In summary, they report a robust bidirectional association in EXSCEL participants confirming a greater risk of SHEs after CV events as well as a greater risk of CV or all-cause death events after SHEs. These findings support our view of an existing common at-risk polymorbid and potentially frail type 2 diabetes patient phenotype, susceptible to both SHEs and CV events. These vulnerable patients with high comorbidity scores after a first CV event in conjunction with heart failure, advanced kidney disease, older age, longer duration of diabetes, and tendency to be on insulin and on higher doses warrant special consideration, including careful dosing of insulin therapy.

Dr. V●●●●●●j D●●●i
Dr. V●●●●●●j D●●●i Legal Medicine
For the sake of new doctors: Though I am not an authority in the branch of medicine dealing with hypoglycemia and cardiovascular diseases, it is basic knowledge that the hypoglycemia relevant here in such situations is DRUG-INDUCED HYPOGLYCEMIA.
Mar 4, 2020Like