A retrospective study showed that, in patients with type 2 diabetes mellitus presenting with acute ischemic stroke, prior and continued use of sulfonylurea drugs as part of the treatment regimen for diabetes was associated with significantly better neurological and functional outcomes at discharge compared with patients whose diabetes was managed without the use of sulfonylurea drugs.110
Notably, the stroke subtype was very important for observing a salutary effect of sulfonylureas: no patient with a lacunar stroke benefited; all of the benefit was observed in patients with nonlacunar strokes.
Maintaining the use of the sulfonylurea drug after presenting with stroke was also crucial. The cohort of patients studied by Kunte et al.110
was actually a subgroup of patients previously reported by Weih et al.
which had included all diabetic patients presenting with acute ischemic stroke who had used a sulfonylurea drug before stroke, regardless of whether the drug was continued after hospitalization. In the combined cohort (patients still taking a sulfonylurea drug plus patients who stopped sulfonylurea drug after hospitalization), overall outcomes were less favorable, with only a nonsignificant trend toward improvement in neurological deficit by the time of discharge.
Another retrospective study suggesting possible protective effects of sulfonylurea drugs in diabetic patients with acute ischemic stroke was presented at an International Stroke Conference; however, this study also examined separately a subgroup of patients who received rt-PA.112
The data were from the Registry of the Canadian Stroke Network and concerned patients presenting to 11 stroke centers in Ontario between July 1, 2003, and March 31, 2008. Of the 15,814 patients screened, 2,448 with diabetes were admitted to hospital within 24 h of symptom onset. Information on medication use during the 48 h or more after admission was available for these patients.
Of the 2,448 patients, 1,469 had not been on and were not started on a sulfonylurea (group A); 729 had been on and were kept on a sulfonylurea (group D). Age (72.6 versus 72.6), gender (45% versus 39% female), admission serum glucose (9.7 ± 4.3 versus 11.1 ± 4.6 mmol/L), and thrombolysis (15% versus 12%) were reasonably balanced for groups A versus D, respectively. The likelihood of in-hospital mortality was less for patients in group D compared with group A (odds ratio, 0.51; 95% CI, 0.37–0.71; P < 0.05). The likelihood of neurological worsening was less for patients in group D compared with group A (odds ratio, 0.70; 95% CI, 0.55–0.89; P < 0.05).
Of the 2,448 patients, 358 were managed with rt-PA. These patients were dichotomized as previously discussed into group A (had not been on and were not started on a sulfonylurea) and group D (had been on and were kept on a sulfonylurea). The baseline characteristics of these patients were not analyzed separately. The likelihood of in-hospital mortality was less for patients in group D compared with group A (odds ratio, 0.30; 95% CI, 0.12–0.73; P < 0.05). The likelihood of neurological worsening was less for patients in group D compared with group A (odds ratio, 0.52; 95% CI, 0.28–0.98; P < 0.05). Although it is not known how well groups A and D were balanced regarding baseline characteristics, these findings are noteworthy, suggesting that the use of sulfonylureas may be beneficial in the context of rt-PA–aided recanalization/reperfusion following acute ischemic stroke.
The findings from the retrospective studies reviewed earlier, both without and with rt-PA, are limited to patients with diabetes mellitus. However, diabetic patients comprise one-third of stroke patients, diabetics are among those who suffer the worst outcomes from stroke, and stroke in diabetics has a high rate of recurrence,113,114
making it difficult to overestimate the importance of improving outcomes in this subgroup of stroke patients. A convergence of data suggests that an increased risk of symptomatic hemorrhagic transformation is a major factor in the poorer outcomes observed in diabetic patients,115,116
making the findings of these retrospective studies highly pertinent.