Daniel M. Keller, PhD

Among patients with atrial fibrillation (AF), initiation of statins soon after diagnosis was protective against stroke and related vascular events, and longer duration of use was associated with greater protection, a new cohort study shows.

Statin use was associated with lower risks of ischemic stroke or systemic embolism, hemorrhagic stroke, and transient ischemic attack (TIA), regardless of whether patients were also taking anticoagulant medications.

Lead author Jiayi Huang, a PhD student at Hong Kong University at Shenzhen Hospital, Shenzhen, China, concluded that the study's findings support the use of statins to prevent stroke for patients with new-onset AF.

"The findings have important clinical implications, particularly given that in atrial fibrillation, patients' ischemic strokes are often fatal or disabling and have a high risk of recurrence," she said.

The results were presented in a moderated poster session at the European Heart Rhythm Association (EHRA) 2023 in Barcelona and are available online.

Widely Prescribed

Anticoagulant drugs are prescribed to lower the fivefold increased risk of stroke among individuals with AF compared with those without AF, but the therapy does not eliminate the higher risk, Huang explained. And although statins are widely prescribed to reduce the likelihood of myocardial infarction and stroke, "the benefit of statins for stroke prevention in patients with atrial fibrillation has been unclear," she said.

Huang and colleagues analyzed data from 51,472 patients newly diagnosed with AF between 2010 and 2018. The population was divided into statin users (n = 11,866), defined as patients who had taken statins for at least 19 consecutive days in the first year after AF diagnosis, and statin nonusers (n = 39,606), based on whether they were prescribed statin therapy after their first diagnosis of AF.

The median age of the cohort was 74.9 years, and 47.7% were women. The investigators used statistical methods to balance baseline covariates between the two groups.

The primary outcomes were ischemic stroke or systemic embolism, hemorrhagic stroke, and TIA. Median follow-up was 5.1 years.

Statin use was associated with a significantly lower risk of all outcomes compared with nonuse. Statin users had a 17% reduced risk of ischemic stroke or systemic embolism, a 7% reduced risk of hemorrhagic stroke, and a 15% rate of reduced risk of TIA, Huang reported.

Table.1  Outcomes With Stroke and Related Events by Statin Use

"We also found long-term statin use was associated with greater protection than short-term use," she said. For statin use of 6 years or longer, in comparison with use of 3 months to 2 years, the risk of ischemic stroke or systemic embolism was lowered by 43%; for hemorrhagic stroke, it was lowered by 44%, and for TIA, it was lowered by 42%.

These associations were consistent regardless of whether patients used anticoagulant medications or the type of anticoagulant.

Oussama Wazni, MD, MBA, section head of cardiac electrophysiology and pacing at the Cleveland Clinic in Ohio, was a moderator of the poster session at which Huang presented her study. In speaking with theheart.org | Medscape Cardiology, he called the study "very important."

"The message should be that all patients who have atrial fibrillation should be checked for cholesterol levels, and we should consider placing them on statins," he said. "Is there an opportunity? Probably there is, and that's why we're seeing this effect in this group of patients."

When asked about a possible mechanism by which statins produced the effects seen in the study, he pointed to LDL lowering and possibly an effect on inflammation. "If a patient had a carotid atheroma, for example, maybe it helped with that," he said. Previous work has shown that inflammation is related to or is associated with higher risk of thrombogenic effects, including MI or stroke.

It may be a bit less clear how statins reduced the incidence of hemorrhagic strokes, but Wazni proposed that some strokes could have started as an ischemic stroke "and then had hemorrhagic conversion, so we don't have the granularity in here to know whether that was the case or not," he said.

Given the fact that the effect was stronger the longer a patient had been taking a statin, Wazni said that if a patient is tolerating the drug well, there should be no reason to discontinue it, regardless of age.

He said the study provides "welcome data and evidence because it's pointing in the right direction," but prospective studies would be useful "so that we can see what is driving what. Otherwise, this is just an association."

The study was supported by Sanming Project Shenzhen. Huang and Wazni have disclosed no relevant financial relationships.