Lower target LDL after stroke prevents 25% of events at 5 years
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During the 5 years after a stroke, targeting LDL of less than 70 mg/dL prevented more than one-quarter of major CV events, recurrent cerebral infarction or urgent carotid revascularization and recurrent cerebral infarction or hemorrhage vs. an LDL target of less than approximately 100 mg/dL.
According to new data from the Treat Stroke to Target trial presented at the International Stroke Conference, the target LDL of less than 70 mg/dL in the 5-year period after stroke was associated with lower risk for the primary endpoint of stroke, MI, new symptoms requiring urgent coronary or carotid revascularization and CV death compared with target LDL of less than 100 ± 10 mg/dL (9.6% vs. 12.9%; HR = 0.74; 95% CI, 0.75-0.94).
The lower target LDL was also associated with reductions in cerebral infarction or urgent carotid revascularization (27%; P = .046), cerebral infarction or intracranial hemorrhage (28%; P = .023), and the primary outcome plus intracranial hemorrhage (25%; P = .022) vs. the higher target LDL.
The findings were simultaneously published in Stroke.
“In patients with ischemic stroke associated with atherosclerotic disease, as compared to a target LDL of 100 mg/dL, targeting LDL of less than 70 mg/dL during 5.3 years avoided one subsequent major vascular event in four and one ischemic stroke or intracranial hemorrhage in four without increasing the risk of intracranial hemorrhage, with a number needed to treat of 30, meaning that if you treat 30 patients you will avoid one stroke,” Pierre Amarenco, MD, of the department of neurology and stroke center at Bichat Hospital, University of Paris, said during the presentation. “This is a very important achievement for future guidelines.”
In other findings, intracranial hemorrhages occurred in 1.2% of patients assigned to LDL less than 70 mg/dL and in 1% of patients assigned to LDL less than 100 ± 10 mg/dL (HR = 1.17; 95% CI, 0.53-2.62).
Patients with proven ischemic stroke
“In a subanalysis, we found a strange result in patients with proven ischemic stroke, having a 37% relative risk reduction and no apparent benefit in patients with transient ischemic attack, that is, no ischemia proven on a brain imaging, with a significant interaction. It’s difficult to explain that,” Amarenco said during his presentation. “Perhaps there is too much noise in the diagnosis of transient ischemic attacks. This is possible and, in future trials, we should concentrate on patients with proven ischemic stroke.”
For the Treat Stroke to Target trial, researchers assigned French and Korean patients with stroke to LDL targets of less than 70 mg/dL (mean age, 67 years; 68% men; 19% with diabetes) or 100 ± 10 mg/dL (mean age, 68 years; 69% men; 18% with diabetes) to evaluate the benefit of targeted LDL control with the aim of secondary CV event prevention. Researchers treated patients with statin and dosage of their choice, adding ezetimibe if needed. The present analysis included only the patients from France.
Future hypothesis
“As we use more potent drugs than statins or ezetimibe, like PCSK9 inhibitors, we would probably have a greater effect size,” Amarenco said during his presentation. “This is a hypothesis for the future, but this is a very important observation.” – by Scott Buzby
References:
Amarenco P, et al. LB9. Presented at: International Stroke Conference; Feb. 19-21, 2020; Los Angeles.
Amarenco P, et al. Stroke. 2020;doi:STROKE/2019/028718R1.
Disclosures: Amarenco reports he received grant support from AstraZeneca, Boston Scientific, Bristol-Myers Squibb, Merck, Pfizer, Sanofi and the French government; consultant fees from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boston Scientific, Daiichi-Sankyo, Fibrogen, Gilead, GlaxoSmithKline, Kowa, Merck, Pfizer, Portola and Shin Poong; and lecture fees from Amgen, Bayer and Pfizer. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Larry B. Goldstein, MD, FAAN, FANA, FAHA
The primary report was published in the New England Journal of Medicine earlier this year (Amarenco P, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa1910355.) and showed the benefit of treatment with a statin targeting an LDL of approximately 70 mg/dL compared with 100 mg/dL on reducing major vascular events in participants who had an ischemic stroke or TIA related to atherosclerosis within the prior 3 months (22% reduction). The trial was conducted in France and Korea, which started enrollment later and where follow up was shorter (5.3 vs. 2 years). Although there was no statistical heterogeneity based on country, there was no significant benefit in Korea. An exploratory analysis focused on France found a 26% reduction in major vascular events. The participants from Korea will continue to be followed to determine whether they also benefit. Overall, the results are consistent with exploratory analyses of the SPARCL trial that found a greater benefit with achieving an LDL of approximately 70 mg/dL and support this therapeutic target.
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