SGLT-2 inhibitor did not decrease risk of stroke in diabetic patients
Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk
Literature - Zinman B, Inzucchi SE, Lachin, ScD JM, et al. - Stroke. 2017;48: published online ahead of printBackground
Diabetes mellitus (DM) patients have a 2-fold increased risk of stroke compared with individuals without DM [1]. With the exception of pioglitazone and semaglutide, intensive or specific glucose-lowering agents have not significantly reduced the risk of stroke in type 2 DM (T2DM) patients [2-5].
In this analysis of 7020 patients enrolled in the EMPA-REG OUTCOME trial, the impact of empagliflozin versus placebo on cerebrovascular events was evaluated.
Main results
- There was no significant difference between empagliflozin and placebo in the occurrence of stroke (HR 1.18, 95% CI 0.89–1.56, P=0.26).
- The proportion of patients with recurrent stroke during the trial was similar between the empagliflozin and placebo groups (0.3% vs 0.3%).
- Nonfatal disabling stroke was reported in 0.2% of patients on empagliflozin and 0.3% of patients on placebo (HR 0.82, 95% CI 0.30–2.26, P=0.70).
- Fatal stroke was reported in similar proportions of patients in the empagliflozin and placebo groups (0.3 and 0.5%, respectively, HR 0.72, 95% CI 0.33–1.55, P=0.40) as was the composite of non-fatal disabling stroke or fatal stroke (0.6% and 0.7%, respectively, HR 0.81, 95% CI, 0.43–1.50, P=0.50).
- There was no significant difference in the risk of TIA (HR 0.85, 95% CI 0.51–1.42, P=0.54) or the composite of stroke or TIA (HR 1.05, 95% CI 0.82–1.35, P=0.87) with empagliflozin versus placebo.
- Systolic blood pressure (SBP) decreased in patients treated with empagliflozin (mean change from baseline to last value on treatment −3.3 [SE 0.3] mmHg), but returned to its baseline level at follow-up (30 days after end of treatment).
- Patients with the largest SBP decreases from baseline (≥30 mmHg) did not have an increased risk of stroke compared with other patients.
- In the empagliflozin group, haematocrit increased during treatment (mean change from baseline to last value on treatment 3.61% [SE 0.06]), but decreased toward baseline at follow-up (30 days after end of treatment).
- Patients with the largest increases from baseline in haematocrit (increases ≥90th percentile, which corresponded to a change in haematocrit of 9 percentage points) did not have an increased risk of stroke compared with patients not meeting this threshold.
- The risk of stroke was comparable between patients with and without atrial fibrillation at baseline or during the study in the placebo and empagliflozin groups.
Conclusion
In T2DM patients at high cardiovascular risk enrolled in the EMPA-REG OUTCOME trial, empagliflozin, when compared with placebo, was not associated with either a reduction or an increase in the risk of cerebrovascular events.
References
1. Emerging Risk Factors Collaboration; Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–2222.
2. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ. 2011;343:d4169.
3. Green JB, Bethel MA, Armstrong PW, et al; TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232–242.
4. Scirica BM, Bhatt DL, Braunwald E, et al; SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–1326.
5. White WB, Cannon CP, Heller SR, et al; EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327–1335.
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