Monday, December 16, 2013

Does hypoglycaemia increase the risk of cardiovascular events? A report from the ORIGIN trial


Does hypoglycaemia increase the risk of cardiovascular events? A report from the ORIGIN trial

Abstract

Aims Hypoglycaemia caused by glucose-lowering therapy has been linked to cardiovascular (CV) events. The ORIGIN trial provides an opportunity to further assess this relationship.
Methods and results A total of 12 537 participants with dysglycaemia and high CV-risk were randomized to basal insulin glargine titrated to a fasting glucose of ≤5.3 mmol/L (95 mg/dL) or standard glycaemic care. Non-severe hypoglycaemia was defined as symptoms confirmed by glucose ≤54 mg/dL and severe hypoglycaemia as a requirement for assistance or glucose ≤36 mg/dL. Outcomes were: (i) the composite of CV death, non-fatal myocardial infarction or stroke; (ii) mortality; (iii) CV mortality; and (iv) arrhythmic death. Hazards were estimated before and after adjustment for a hypoglycaemia propensity score. During a median of 6.2 years (IQR: 5.8–6.7), non-severe hypoglycaemic episodes occurred in 41.7 and 14.4% glargine and standard group participants, respectively, while severe episodes occurred in 5.7 and 1.8%, respectively. Non-severe hypoglycaemia was not associated with any outcome following adjustment. Conversely, severe hypoglycaemia was associated with a greater risk for the primary outcome (HR: 1.58; 95% CI: 1.24–2.02, P < 0.001), mortality (HR: 1.74; 95% CI: 1.39–2.19, P < 0.001), CV death (HR: 1.71; 95% CI: 1.27–2.30, P < 0.001) and arrhythmic death (HR: 1.77; 95% CI: 1.17–2.67, P = 0.007). Similar findings were noted for severe nocturnal hypoglycaemia for the primary outcome and mortality. The severe hypoglycaemia hazard for all four outcomes was higher with standard care than with insulin glargine.
Conclusion Severe hypoglycaemia is associated with an increased risk for CV outcomes in people at high CV risk and dysglycaemia. Although allocation to insulin glargine vs. standard care was associated with an increased risk of severe and non-severe hypoglycaemia, the relative risk of CV outcomes with hypoglycaemia was lower with insulin glargine-based glucose-lowering therapy than with the standard glycaemic control. 

4 comments:

  1. I also included the original origin trial paper from 2012 NEJM in Zotero. "Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia" is the paper.

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  2. Be sure to check out the following link in Clinical Endocrinology News and evaluate what's being said. For example: ' "What was reassuring was that while insulin glargine caused more hypoglycemic events" compared with standard treatment in these patients, "the absolute number of fatal events was still lower with insulin, showing insulin is a very safe treatment," said Dr. Lars Rydén, professor of cardiology at the Karolinska Institute and a coinvestigator with Dr. Mellbin. ' http://www.clinicalendocrinologynews.com/cme/click-for-credit-articles/single-article/insulin-triggered-hypoglycemia-poses-less-danger/3d682d9cb09d7e51a83a2ebaf910a229.html

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  3. Cardiologists may be parroting this, but is it true? ' "Hypoglycemia caused by insulin glargine–mediated glucose lowering is unlikely to cause cardiovascular outcomes," Dr. Linda G. Mellbin said at the European Society of Cardiology Congress 2013. '

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  4. The methods for the Origin trial can be found here on p. 30. http://www.nejm.org/doi/suppl/10.1056/NEJMoa1203858/suppl_file/nejmoa1203858_appendix.pdf

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