Antithrombotic treatment for migraine in patients with patent foramen ovale: multicentre, randomised, active controlled, open label trial.

Methods

Investigator initiated, multicentre, prospective, randomised, active controlled, open label clinical trial with blinded outcome assessment and hierarchical hypothesis testing.

研究者发起的多中心前瞻性随机活性对照开放标签临床试验，具有盲法结果评估和分层假设检验。

Secondary and tertiary care hospitals across 39 centres in China.

中国39个中心的二级和三级医院。

1000 adults aged 18-64 years with a diagnosis of migraine for more than one year, experiencing at least four migraine days per month, and with PFO confirmed by echocardiography.

1000名年龄在18-64岁之间，被诊断为偏头痛超过一年，每月至少有四天偏头痛发作，并且通过超声心动图确认存在卵圆孔未闭的成人。

All participants completed a 12 week screening period before randomisation during which eligibility was confirmed and baseline headache data were prospectively recorded.

所有参与者在随机分组前完成了为期12周的筛查期，在此期间确认了资格并前瞻性地记录了基线头痛数据。

Participants with previous stroke, transient ischaemic attack, intracranial haemorrhage, non-PFO right-to-left shunt, or contraindications to study drugs were excluded.

排除了既往有中风、短暂性脑缺血发作、颅内出血、非PFO右向左分流或对研究药物有禁忌症的参与者。

Of the randomised participants, 984 (75.1% female) were included in the full analysis set.

在随机分配的参与者中，984名（女性占75.1%）被纳入完整分析集。

After the screening phase, participants were randomised in a 1:1:1:1 ratio to receive aspirin (300 mg once daily), clopidogrel (75 mg once daily), rivaroxaban (20 mg once daily), or metoprolol (25 mg twice daily) for 12 weeks.

筛选阶段后，参与者按照1:1:1:1的比例被随机分配，分别接受阿司匹林（每日一次300毫克）、氯吡格雷（每日一次75毫克）、利伐沙班（每日一次20毫克）或美托洛尔（每日两次25毫克）治疗，持续12周。

No additional preventive migraine treatments were permitted during the intervention period.

在干预期间，不允许使用额外的预防性偏头痛治疗。

The primary outcome was the proportion of participants achieving a ≥50% reduction in monthly migraine days or attacks from baseline to weeks 9-12.

主要结果是参与者从基线到第9-12周实现每月偏头痛天数或发作减少≥50%的比例。

Safety outcomes included bleeding and other adverse events.

安全性结果包括出血和其他不良事件。

Results

For the primary endpoint, aspirin, clopidogrel, and rivaroxaban were all non-inferior to metoprolol.

对于主要终点，阿司匹林、氯吡格雷和利伐沙班均不劣于美托洛尔。

Responder rates were 61.7% (148/240) with aspirin, 66.8% (157/235) with clopidogrel, 78.4% (185/236) with rivaroxaban, and 61.8% (144/233) with metoprolol.

使用阿司匹林的反应者率为61.7%（148/240），使用氯吡格雷的为66.8%（157/235），使用利伐沙班的为78.4%（185/236），使用美托洛尔的为61.8%（144/233）。

Rivaroxaban further showed a statistically higher responder rate than metoprolol, with an absolute difference of 16.2% (98.33% confidence interval6.0 to 26.4; P<0.001).

利伐沙班显示出比美托洛尔更高的反应者率，绝对差异为16.2%（98.33%置信区间6.0至26.4；P<0.001）。

Among secondary endpoints, rivaroxaban was associated with greater reductions in migraine days and attacks, higher rates of complete migraine cessation, and greater improvements in migraine specific quality-of-life scores than metoprolol.

在次要终点中，利伐沙班与减少偏头痛天数和发作次数、更高的完全停止偏头痛率以及在偏头痛特异性生活质量评分上的更大改善相关，这些效果均优于美托洛尔。

No major bleeding events occurred.

未发生重大出血事件。

Conclusions

The antithrombotic agents evaluated in this trial (aspirin, clopidogrel, and rivaroxaban) were all non-inferior to metoprolol for responder rate in participants with PFO and migraine.

本试验评估的抗血栓药物（阿司匹林、氯吡格雷和利伐沙班）对于有卵圆孔未闭和偏头痛的参与者，其反应率均不低于美托洛尔。

Rivaroxaban also showed superior responder rates over metoprolol without an increase in major bleeding events.

利伐沙班在不增加主要出血事件的情况下，其反应率也优于美托洛尔。

trial_registration

ClinicalTrials.gov NCT05546320.

ClinicalTrials.gov NCT05546320。