TST 5-year data: LDL <70 cuts risk of recurrent stroke

Treating stroke patients to a target LDL cholesterol (LDL-C) of <70 mg/dL significantly reduced the risk of recurrent stroke and other major cardiovascular (CV) events at 5 years, without raising the risk of intracranial haemorrhage (ICH), a subanalysis of the French cohort in the TST* trial has shown.

“Current AHA/ASA** guidelines recommend ‘intense’ statin therapy after an ischaemic stroke of atherosclerotic origin but does not stipulate a target level of LDL-C,” said Professor Pierre Amarenco of Bichat University Hospital, Paris, France during the ISC 2020 Meeting. “Therefore, there was uncertainty about the target level of LDL-C that is appropriate to reduce CV events after stroke.”

Analysing the French cohort of the TST trial with a median follow-up of 5.3 years, the investigators found that the primary composite outcome*** occurred less frequently in patients treated to an LDL-C target of <70 vs 100 ± 10 mg/dL (9.6 percent vs 12.9 percent; hazard ratio [HR], 0.74; p=0.019). [ISC 2020, abstract LB 19; Stroke 2020;doi:10.1161/STROKEAHA.119.028718]

“The positive result of the TST trial with a number needed to treat of 30 sets a new target range for LDL-C to achieve of <70 mg/dL during 5 years after a stroke of atherosclerotic origin,” said Amarenco.

He also pointed out that the result was obtained while other risk factors were also controlled at optimal levels, such as blood pressure (mean 135/75 mm Hg), HbA1c <7 percent, and active smoking status, which dropped from 30 percent at baseline to 5 percent during the study.

The finding was consistent with that in the overall population, which included 2,148 French and 742 Korean participants. The primary composite outcome was also reduced with more intensive vs less intensive LDL-C lowering (rates of primary outcome, 8.5 percent vs 10.9 percent; HR, 0.78; p=0.04), which has been reported previously. [N Engl J Med 2020;382:9-19]

The current subanalysis focused only on the French cohort as it was larger with a longer median follow-up of 5.3 years, compared with 2.0 years in the Korean patients. The longer follow-up was also comparable to the SPARCL^# trial (4.9 years median follow-up), on which the guideline recommendation for an intense LDL-lowering therapy after an ischaemic stroke was based on.

Participants in the subanalysis were 2,148 French patients (mean 67 years, ~68 percent male) with ischaemic stroke of atherosclerotic origin, who were randomized 1:1 to a target LDL-C level of <70 vs 100±10 mg/dL. On average, the LDL-C levels achieved were 66 mg/dL for the more aggressive target and 96 mg/dL for the less aggressive target.

The composite of primary outcome plus ICH was similarly reduced by 25 percent (p=0.021), as was cerebral infarction or ICH (all strokes; reduction, 28 percent; p=0.023).

“Targeting a LDL-C of <70 mg/dL during 5.3 years avoided one subsequent major vascular event in four patients, as well as one ischaemic stroke or ICH in four patients, without increasing the risk of ICH … compared with a target LDL-C of 100 mg/dL,” reported Amarenco. ICH occurred in 13 and 11 patients, respectively (HR, 1.17; p=0.70).

He also believed that further reduction in LDL-C may provide further benefit, without any lower threshold, as suggested by the CTT meta-analysis. [Lancet 2010;376:1670-1681]

“These studies and our trial results suggest that [further] lowering LDL-C with new, more potent lipid lowering drug in future randomized clinical trial may further address the residual risk in patients with stroke,” the investigators said.

“[But for now, physicians] may find useful in practice to target a number, such as <70 mg/dL as a first objective in prevention of new stroke, as suggested by our results,” they stated.