Liraglutide cardioprotection replicated in real-world data
medwireNews: Registry data from Denmark and Sweden uphold the cardioprotective effects of liraglutide observed in randomized trials, with the strongest effects seen in patients with established cardiovascular disease.
“Although results from observational clinical effectiveness studies should be considered complementary, rather than comparable, to evidence from randomised trials, these findings suggest that the cardiovascular benefit of liraglutide seen in the LEADER trial might also be apparent in patients seen in routine clinical practice,” write the study authors in The Lancet Diabetes & Endocrinology.
Björn Pasternak (Karolinska Institutet, Stockholm, Sweden) and co-workers assessed rates of the 3-point major adverse cardiovascular events endpoint (nonfatal myocardial infarction and stroke, and cardiovascular death), as was used in the majority of the cardiovascular outcomes trials.
This occurred at a rate of 14.0 per 1000 person‑years among 23,402 new users of liraglutide during an average 3.5 years of follow-up and at a rate of 15.4 per 1000 person‑years among the same number of new users of dipeptidyl peptidase (DPP)-4 inhibitors during an average follow-up of 3.2 years.
The researchers chose DDP-4 inhibitors as the comparator medications because of their neutral cardiovascular effect in clinical trials. Users of these medications were matched to the liraglutide users by age, sex, and their propensity to be prescribed liraglutide.
The patients were aged an average of around 59.5 years and 59% were men. A third were insulin-dependent, just over a quarter were using sulfonylureas, 1% were taking a sodium-glucose cotransporter 2 inhibitor, and 5% were using other diabetes medications such as glitazones.
In contrast with the cardiovascular outcomes clinical trial cohorts, the majority of patients were free of overt cardiovascular disease, with rates of between 4% and 16% for heart failure, stroke, acute coronary syndromes, and other ischemic heart disease.
There was evidence that patients with established cardiovascular disease derived the greatest benefit from liraglutide, at a significant 19% risk reduction compared with a nonsignificant 4% reduction among patients without established disease. The test for interaction (ie, a significantly different response to treatment between the two subgroups) just missed significance, with a p value of 0.057.
There were very similar findings for age, with patients aged 65 years or older having a larger cardiovascular risk reduction than younger patients. However, the authors of an accompanying commentary believe that “this finding might be due to a higher baseline cardiovascular risk and hence larger effect size in older patients.”
Guntram Schernthaner (Rudolfstiftung Hospital, Vienna, Austria) and Marie Helene Schernthaner-Reiter (Medical University of Vienna, Austria) say the study “provides encouraging new data confirming a cardiovascular benefit of liraglutide in a large and overall relatively low-risk population that is representative of everyday clinical practice.”
But they also highlight the need for more studies of modern antidiabetes medications in patients with relatively low cardiovascular risk.
“Findings from such studies will allow us to determine which antihyperglycaemic drug should be used in combination with metformin in low-risk patients without established cardiovascular disease,” they write.
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