This article is more than 5 years old. Information may no longer be current.
Lower LDL target beneficial after stroke
Click Here to Manage Email Alerts
PHILADELPHIA — Among patients with signs of atherosclerosis following stroke or transient ischemic attack, those who achieved a target LDL level of less than 70 mg/dL had lower risk for subsequent CV events than patients achieving LDL levels between 90 and 110 mg/dL, according to findings presented at the American Heart Association Scientific Sessions.
In the Treat Stroke to Target trial of 2,860 patients with stroke or TIA (mean LDL at baseline, 135 mg/dL), those assigned to a regimen to treat LDL level to a target of < 70 mg/dL had a lower incidence of the primary endpoint of subsequent stroke, MI, urgent revascularization, or CV death at a median follow-up of 3.5 years compared with patients assigned a regimen to achieve LDL 90 mg/dL to 110 mg/dL (adjusted HR = 0.78; 95% CI, 0.61-0.98).
The primary endpoint occurred in 8.5% of the lower-target group, which achieved a mean LDL of 65 mg/dL, and in 10.9% of the higher-target group, which achieved a mean LDL of 98 mg/dL, according to the researchers.
The findings were simultaneously published in The New England Journal of Medicine.
The trial was stopped for administrative reasons after 277 of an anticipated 385 endpoint events had occurred, according to the presentation.
“With the limitation that we had to stop the trial ... it showed that after an ischemic stroke with evidence of atherosclerosis, the target LDL cholesterol of less than 70 mg/dL compared to 100 mg/dL reduces the risk of subsequent cardiovascular events,” 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, said during the presentation. “We also saw no significant increase in intracranial hemorrhage or in newly diagnosed diabetes.”
Methods and limitations
In this parallel-group trial conducted in France and South Korea, all patients (mean age, 67 years; 68% men) had evidence of cerebrovascular or coronary artery atherosclerosis and received a statin and/or ezetimibe.
“The extension of the trial by the sponsor allowed follow-up for every patient until the end of the trial rather than for 3 years, as initially planned,” the researchers wrote in NEJM. “This allowed for the observed 277 events to provide a sufficient power to detect a 25% lower relative risk in the lower-target group, as hypothesized in the original trial design.”
Looking forward
“In terms of future directions for this line of investigation, one could consider what we should do about patients who have evidence of silent infarctions on imaging and should they be treated with statins long or lipid-lowering long-term,” Mitchell Elkind, MD, MS, MPhil, professor of neurology at Columbia University College of Physicians and Surgeons, NY, said during the presentation. “Then there are patients with intracerebral hemorrhage who might have concomitant atherosclerotic disease, so how do we manage those patients given the potential for increase in bleeding as well?”
“Despite the limitations of this trial, the results could help to guide clinicians in the use of statins in patients with cardiovascular disease who have had strokes,” Lawrence R. Wechsler, MD, Henry B. Higman professor and chair of the department of neurology at the University of Pittsburgh Schools of the Health Sciences, wrote in a related editorial in NEJM. “The trial provides evidence to support the original concept of statins as an agent to reduce cardiovascular risk, primarily by reducing cholesterol levels. Is LDL cholesterol the only and best target to reach this goal? That question is subject to further study to fine-tune our approach in terms of risks and benefits.” – by Scott Buzby
References:
Amarenco P, et al. Late Breaking Science VI: New Frontiers in Lipid Therapy. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2019; Philadelphia.
Amarenco P, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1910355.
Wechsler LR. N Engl J Med. 2019;doi:10.1056/NEJMoa1914757.
Disclosures: Amarenco reports he received grants and/or personal fees from AstraZeneca, Bayer, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Fibrogen, Gilead, GlaxoSmithKline, Kowa, Merck, Ministère des Affaires Sociales et de la Santé, Pfizer, Portola, Sankyo, Sanofi and Shing Poon. Wechsler reports he received personal fees from Biogen. Elkind reports he is an expert witness for LivaNova, received honoraria from UptoDate and received research support from Bristol-Myers Squibb/Pfizer and Roche.