Canagliflozin may reduce stroke risk in patients with T2D, CVD
An additional benefit of canagliflozin when administered to patients with type 2 diabetes (T2D) and high cardiovascular (CV) risk may be a reduced risk of stroke, according to results from the CANVAS* Program.
“There were too few events to separately define the effects of canagliflozin on stroke, but these analyses show that benefit is more likely than harm,” said the researchers.
The 10,142 participants in the CANVAS Program had T2D and high CV risk at baseline (mean age 63.3 years, 35.8 percent female, mean T2D duration 13.5 years, 65.6 percent with CV disease history) and were randomized to receive either canagliflozin (100 or 300 mg) or placebo. Of these, 19.3 percent (n=1,958) had cerebrovascular disease history (stroke or transient ischaemic attack [TIA]) at baseline.
Over the mean 188.2-week follow-up period, 309 patients experienced either a fatal or nonfatal stroke, of whom 123 had a history of stroke or TIA at baseline. The rate of strokes during follow up was lower among those on canagliflozin compared with placebo (7.93 vs 9.62 per 1000 patient-years, hazard ratio [HR], 0.87, 95 percent confidence interval [CI], 0.69–1.09). [Stroke 2019;50:396-404]
This reduced risk may have been driven by a significantly lower risk of haemorrhagic stroke among canagliflozin compared with placebo recipients (0.53 vs 1.29 per 1000 patient-years, HR, 0.43, 95 percent CI, 0.20–0.89), though the overall incidence of haemorrhagic stroke was low (n=30). There was a numerical but not statistically reduced risk of ischaemic stroke among canagliflozin compared with placebo recipients (n=253, 6.70 vs 7.51 per 1000 patient-years, HR, 0.95, 95 percent CI, 0.74–1.22), while no benefit was conferred by canagliflozin on stroke of undetermined cause (n=29, 0.80 vs 0.79 per 1000 patient-years, HR, 1.04, 95 percent CI, 0.48–2.22).
Subgroup analysis showed that the effect of canagliflozin on stroke risk appeared to particularly benefit older patients (pinteraction=0.006), patients with lower estimated glomerular filtration rate (pinteraction=0.005), and patients on antithrombotics (pinteraction=0.04), though baseline antithrombotic use did not affect haemorrhagic stroke risk.
“The CANVAS Program was not powered to examine the individual contributions of stroke, myocardial infarction, and CV death to the primary outcome, but the observed effect on stroke events is consistent with that initially anticipated on the basis of the known blood pressure [BP]-lowering effect of the compound,” said the researchers.
The significant reduction in haemorrhagic stroke, despite the limited number of cases, reflects the BP-lowering mechanism of canagliflozin, with haemorrhagic stroke more likely influenced by elevated BP than ischaemic stroke, with no apparent benefit demonstrated by canagliflozin on the latter, they said.