LDL-C levels do not predict ischaemic stroke in AF patients on DOACs

No association exists between low-density lipoprotein cholesterol (LDL-C) levels and ischaemic stroke risk among patients with atrial fibrillation (AF) treated with direct oral anticoagulants (DOACs).

“Because LDL-C levels did not improve the stroke prediction of the CHA2DS2-VASc score, our findings support the noninclusion of dyslipidaemia in ischaemic stroke risk stratification of patients with AF,” the researchers said.

This study used the electronic database of Clalit Health Services in Israel and included 21,229 patients with first-time diagnosis of nonvalvular AF treated with DOACs between 2010 and 2017. Participants were categorized according to the CHA₂DS₂-VASc score (1-2, 3-4, 5-6, and 7-9), and each group was further stratified to four subgroups according to LDL-C levels (<70, 70–99, 100–130, and >130 mg/dL).

Finally, the researchers compared ischaemic stroke rates among the four LDL-C subgroups of each CHA₂DS₂-VASc category.

A total of 2,481 ischaemic stroke incidents occurred during 56,467 person-years of follow-up. Higher CHA₂DS₂-VASc score correlated with a significantly higher risk of ischaemic stroke (17.5, 26.9, 46.3, and 94.9 cases per 1,000 person-years for patients with CHA₂DS₂-VASc score of 1-2, 3-4, 5-6, and 7-9, respectively; p<0.001). [Am J Med 2021;134:507-513]

However, no association was found between LDL-C levels and incident ischaemic stroke within each CHA₂DS₂-VASc score group even after a multivariate adjustment. There was also no association seen in subanalyses of patients with previous stroke and those treated with statins.

Previous studies have shown the association of LDL-C with stroke. In addition, intensive lipid-lowering therapy with either potent statins, ezetimibe, or PCSK9 inhibitors was reported to reduce stroke risk in both primary and secondary prevention. [Atherosclerosis 2016;248:123-131; Stroke 2018;49:820-827; Stroke 2012;43:958-966; Heart 2019;105:1149-1159; Atherosclerosis 2016;248:216-218]

“Therefore, the current guidelines recommend that in addition to therapeutic lifestyle changes, treatment with statins is recommended for the primary prevention of ischaemic stroke in patients estimated to have a high cardiovascular risk,” the researchers said. [Stroke 2014;45:3754-3832; Eur Heart J 2020;41:111-188]

The lack of association between LDL-C and incident ischaemic stroke among AF patients in the current study could be explained by some factors.

“Several studies have evaluated the aetiology of ischaemic stroke in patients with AF,” the researchers said. “Many patients with AF have concomitant cardiovascular risk factors.” [PLoS One 2018;13e0201062]

A study on 522 patients with AF and ischaemic stroke who underwent full assessment showed that AF was the cause of stroke in around 80 percent of participants. Of note, dyslipidaemia rates were similar between patients with atherosclerotic or cardioembolic stroke. [Cerebrovasc Dis 2013;36:373-382]

“Another possible explanation is the evidence suggesting that treatment with rivaroxaban may be associated with a significant reduction in major adverse cardiovascular outcomes, including ischaemic stroke in high-risk patients without AF,” the researchers said. [N Engl J Med 2017;377:1319-1330; JAMA Neurol 2020;77:43-48; Lancet 2018;391:219-229]

“These data suggest that DOACs may also prevent noncardioembolic ischaemic stroke,” the added.