BACKGROUND: Following regulatory approval, medical devices may be used “off-label.” Patent foramen ovale (PFO) closure is indicated to reduce recurrent stroke but has been proposed for other indications, including migraine, transient ischemic attack, and diving decompression illness. We sought to evaluate PFO closure rates and indications relative to the timing of regulatory approval and publication of key randomized trials. METHODS: We performed a retrospective cohort study using the OptumLabs Data Warehouse of US commercial insurance enrollees from 2006 to 2019. We quantified PFO closure among individuals with ≥2 years of preprocedure coverage to establish indications, classified hierarchically as stroke/systemic embolism, migraine, transient ischemia attack, or other. RESULTS: We identified 5315 patients undergoing PFO closure (51.8% female, 29.2%≥60 years old), which increased from 4.75 per 100 000 person-years in 2006 to 6.60 per 100 000 person-years in 2019. Patients aged ≥60 years accounted for 29.2% of closures. Procedure volumes corresponded weakly with supportive clinical publications and device approval. Among patients with PFO closure, 58.6% underwent closure for stroke/systemic embolism, 10.2% for transient ischemia attack, 8.8% for migraine, and 22.4% for other indications; 17.6% of patients had atrial fibrillation at baseline; and 11.9% developed atrial fibrillation postprocedure. Those aged ≥60 years and male were less likely to undergo closure for migraine than stroke/systemic embolism. CONCLUSIONS: From 2006 to 2019, PFO closure use was consistently low and corresponded weakly with clinical trial publications and regulatory status. Nearly half of patients underwent PFO closure for indications unapproved by the Food and Drug Administration. Regulators and payers should coordinate mechanisms to promote utilization for approved indications to ensure patient safety and should facilitate clinical trials for other possible indications.

中文翻译：

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批准、证据和“标签外”器械使用：卵圆孔未闭封堵术的故事

背景：经监管部门批准后，医疗器械可以“标签外”使用。卵圆孔未闭 (PFO) 封堵术可减少中风复发，但也被提议用于其他适应症，包括偏头痛、短暂性脑缺血发作和潜水减压病。我们试图评估 PFO 闭合率和与监管部门批准和关键随机试验发表时间相关的适应症。 方法：我们使用 OptumLabs 数据仓库对 2006 年至 2019 年美国商业保险参保者进行了一项回顾性队列研究。我们对术前保险范围≥2 年的个体的 PFO 封堵进行了量化，以确定适应症，按等级分类为中风/全身性栓塞、偏头痛、短暂性脑缺血攻击，或者其他。 结果：我们确定了 5315 例接受 PFO 封堵术的患者（51.8% 为女性，29.2%≥60 岁），从 2006 年的每 10 万人年 4.75 例增加到 2019 年的每 10 万人年 6.60 例。年龄≥60 岁的患者占29.2% 的工厂关闭。手术量与支持性临床出版物和设备批准的对应性较弱。在 PFO 封堵术患者中，58.6% 因中风/全身性栓塞接受封堵术，10.2% 因短暂性脑缺血发作，8.8% 因偏头痛，22.4% 因其他适应症接受封堵术；17.6% 的患者在基线时患有房颤；11.9% 的患者术后出现房颤。与中风/全身性栓塞相比，年龄≥60 岁的男性因偏头痛接受封堵术的可能性较小。 结论：从 2006 年到 2019 年，PFO 封堵器的使用率一直较低，并且与临床试验出版物和监管状况的对应性较差。近一半的患者因未经美国食品和药物管理局批准的适应症而接受了 PFO 封堵术。监管机构和付款人应协调机制，促进已批准适应症的使用，以确保患者安全，并应促进其他可能适应症的临床试验。