P4994Severe hypoglycemia: a marker for worse cardiovascular outcomes? A meta-analysis of randomised controlled trials

Abstract

Abstract Background Observational data have suggested that severe hypoglycemic events increase the risk of subsequent cardiovascular morbidity and mortality but the evidence from randomised studies has been inconsistent. Purpose This meta-analysis evaluates the relationship between severe hypoglycemic events (SHEs) and the subsequent risk of mortality and major adverse cardiovascular events (MACE). Methods PubMed, Embase, and Cochrane Central databases were searched for randomised controlled trials (RCTs) that reported cardiovascular outcomes in patients with diabetes with a history of SHE. Treatment effects and relative standard errors were calculated from the available data. These values were imputed in software R to perform meta-analysis via generic inverse variance method. Results Data from 9 RCTs and 3,462 randomised patients were available. Patients, who suffered a SHE, were found to have a significantly increased risk of subsequent all-cause mortality (HR 2.24; 95% CI 1.70, 2.95; p-value <0.01), cardiovascular mortality (HR 2.32; 95% CI 1.67, 3.22; p-value <0.01), and MACE (HR 1.66; 95% CI 1.35, 2.06; p-value <0.01) compared to the patients without a SHE. An increased risk of subsequent stroke and arrhythmic death (p-value<0.05) were also found. There was no significant association between SHE and the risk of subsequent myocardial infarction and hospitalisation for unstable angina or heart failure. Predictors of severe hypoglycemia Older age, Lower weight, Insulin-treated, CKD, Neuropathy, previous CVD Older age, Females, Lower weight, Insulin-treated, Longer duration of diabetes, CKD, Previous CVD Older age, Females, Lower weight, Insulin-treated, Longer duration of diabetes, CKD, Previous CVD Older age, Females, Insulin-treated, Longer duration of diabetes, CKD Older age, Females, Lower weight, Insulin-treated, CKD Older age, Lower weight, Longer duration of diabetes, CKD, Poor cognition, Previous CVD CKD = Chronic kidney disease; CVD = Cardiovascular disease. Conclusion In patients with diabetes, the occurrence of a SHE was associated with a significantly increased risk of subsequent cardiovascular morbidity and mortality. Further studies are required to explore and circumvent the predictors of SHEs in these patients. Acknowledgement/Funding None