Dual therapy for lower target LDL after stroke reduces risk for events at 5 years

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Dual therapy for lower target LDL after stroke reduces risk for events at 5 years 

An LDL target of less than 70 mg/dL with ezetimibe plus statin therapy was associated with lower risk for subsequent events after stroke/transient ischemic attack at 5 years vs. a target between 90 mg/dL and 110 mg/dL, researchers reported.

In addition, ezetimibe plus statin therapy — dual therapy — for a lower target LDL was not associated with increased risk for intracranial bleeding, according to findings of a post hoc analysis of the Treat Stroke to Target trial published in Stroke.

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“In the lower target group, dual therapy with statin and ezetimibe significantly reduced major vascular events, and the reduction was not significant on the statin monotherapy, as compared with all patients in the higher target group,” Pierre Amarenco, MD, chairman of the department of neurology and the Stroke Center at Bichat Hospital and professor of neurology at Xavier Bichat Medical School and Denis Diderot University in Paris, and colleagues wrote. “This difference was observed although the mean LDL cholesterol achieved was very similar in both groups.”

The Treat Stroke to Target trial

Treat Stroke to Target was a parallel-group trial conducted in France and South Korea and included 2,860 patients with stroke or TIA and evidence of cerebrovascular or coronary artery atherosclerosis (mean age, 67 years; 68% men; mean LDL at baseline, 135 mg/dL). Participants received dual therapy or statin monotherapy and were assigned to an LDL target of less than 70 mg/dL or 90 to 110 mg/dL. The primary endpoint was subsequent stroke, MI, urgent revascularization or CV death at a median follow-up of 3.5 years.

As Healio previously reported, patients with signs of atherosclerosis after stroke or TIA who achieved a LDL level of less than 70 mg/dL had lower risk for subsequent CV events compared with patients achieving LDL between 90 mg/dL and 110 mg/dL (adjusted HR = 0.78; 95% CI, 0.61-0.98).

Dual vs. monotherapy and lower target LDL

For the post hoc analysis, researchers evaluated whether dual therapy or statin monotherapy reduced risk for the primary outcome in patients who achieved a lower target LDL compared with a higher target LDL.

In the group assigned to the lower LDL target, those on dual therapy had higher mean LDL at baseline compared with patients on statin monotherapy (141 vs. 131 mg/dL; P < .001).

Mean achieved LDL was 66.2 mg/dL in the dual therapy group and 64.1 mg/dL in the statin monotherapy group.

Amarenco and colleagues reported that dual therapy for a lower target LDL was associated with lower risk for the primary outcome compared with a higher target LDL (HR = 0.6; 95% CI, 0.39-0.91; P = .016).

However, there was no association between statin monotherapy and lower risk for the primary outcome in the lower LDL target group compared with the higher target (HR = 0.92; 95% CI, 0.7-1.2; P = .52).

Risk for intracranial bleeding was also lower in patients on dual therapy with an LDL target of less than 70 mg/dL compared with all patients with higher target LDL (HR = 0.62; 95% CI, 0.41-0.94; P = .023).

“Explanation for such a different effect between dual therapy and statin monotherapy groups may be a higher baseline mean LDL cholesterol level in the dual therapy group, with consequently greater reduction in LDL cholesterol from baseline,” the researchers wrote. “Indeed, the effect of LDL-lowering therapy has always been associated with the magnitude of the reduction in LDL cholesterol from baseline.”