Lowering LDL cholesterol < 70 mg/dL with Statin and Ezetimibe combo reduces stroke risk: "Treat Stroke to Target" Trial

FRANCE: The results of a post hoc analysis done by a team of researchers concluded that targeting LDL cholesterol of < 70 mg/dL with a dual therapy of statin and ezetimibe compared with 100±10 mg/dL reduces the risk of subsequent stroke in the TST (Treat Stroke to Target) trial.

The study findings are published in the AHA journal "STROKE."

The first trial focusing on cholesterol reduction was the SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Level) randomizing  4731 patients with a history of recent stroke to atorvastatin 80 mg and it lowered 16%  risk of stroke (adjusted hazard ratio, 0.84) after 4.9 years. The second trial after this is the TST Trial.

Putting high-risk stroke patients on maximal statin therapy (fire-and-forget) or adjusting treatment to achieve a target LDL cholesterol (treat-to-target) is a matter of debate even after years of SPARCL.

"Addition of ezetimibe to statin therapy lowers LDL-C and reduces the risk for stroke in patients of the acute coronary syndrome.", as interpreted by IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

According to the American College of Cardiology and the American Heart Association, patients with clinical atherosclerotic cardiovascular disease, including ischemic stroke, receive high-dose statin therapy. The patients at very high risk (multiple major atherosclerotic cardiovascular disease events and additional vascular risk factors) are recommended to target LDL-C to <70 mg/dL by additional agents. These guidelines are supported by TST and mention that lower LDL target levels are achievable with statins with or without ezetimibe, but "LDL-C goal is more important than the choice of statin." This is similar to what is mentioned in the European Society of Cardiology 2020 guidelines.

Considering this, a post hoc analysis was performed by Dr. Pierre Amarenco, MD, at the Department of Neurology and Stroke Centre at Bichat Hospital with a team of researchers to determine the relative effects of dual therapy of statin and ezetimibe and statin monotherapy to achieve lower LDL cholesterol target and reduce the significant vascular events risk. A comparison was made with the higher target group.

The study included schemic stroke patients in the previous three months or had transient ischemic attacks within the last 15 days and a history of cerebrovascular or coronary artery atherosclerosis. The primary outcome measured was the major cardiovascular event. The secondary results measured were myocardial infarction and urgent coronary revascularization, cerebral infarction and urgent carotid and cerebral artery revascularization and intracranial haemorrhage.

In statistical analysis, the Cox regression model was included.

The critical points of the study are:

• 2860 patients enrolled in the study.

• The dual therapy (statin plus ezetimibe) had 529 patients.

• The monotherapy had 896 patients.

• The patients targeting LDL cholesterol < 70mg/dL were compared to those targeting 100±10 mg/dL. This had 1424 patients.

• Patients on dual therapy had a higher baseline LDL cholesterol of 141±38.

• The patients on statin monotherapy had lower baseline LDL cholesterol levels than the dual therapy and were 131±36.

• The achieved LDL cholesterol in patients on dual therapy and monotherapy was 66.2 and 64.1 mg/dL, respectively.

• The primary outcome of dual therapy had a Hazard Ratio of 0.59 and was reduced compared with the higher target group. The P value was 0.016.

• The primary outcome was not reduced in statin monotherapy with HR of 0.92 and P value of 0.56

• Myocardial infarction and urgent coronary revascularization had HR of 0.36 with a P value of 0.057 in dual therapy and 0.87 with a P value of 0.67 in monotherapy.

• The HR for dual therapy was 0.57 (P value 0.037) and 0.93 (P value 0.79 ) for cerebral infarction and urgent carotid and cerebral artery revascularization.

• The intracranial haemorrhage had an HR of 0.62 in dual therapy and 0.95 for monotherapy. The p-values were 0.023 and 0.74, respectively.

• There was no significant increase risk of intracranial bleeding with dual therapy.

Dr. Jong S. Kim said that we support the use of dual therapy. In this secondary analysis of the TNT trial, we recorded a lower risk of major adverse cardiovascular events and the composite of stroke and urgent carotid and cerebral artery revascularization in patients receiving dual therapy to achieve the target of LDL cholesterol <70 mg/dL compared to the patients targeting 100 ± 10 mg/dL.

Reference:

Yield of Dual Therapy With Statin and Ezetimibe in the Treat Stroke to Target Trial Pierre Amarenc Stroke. 2022;0:10.1161/STROKEAHA.122.039728