Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Department of Chronic Diseases and Aging, Norwegian Institute of Public Health, Oslo, Norway.
Pharmacotherapy. 2019 Feb;39(2):150-160. doi: 10.1002/phar.2217. Epub 2019 Feb 8.
Evidence on the cardiotoxicity of nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs), particularly diclofenac and the newer selective cyclooxygenase (COX)-2 inhibitors, has accumulated over the last decade. Our objective was to examine whether the use of NSAIDs in the Nordic countries changed with the emerging evidence, regulatory statements, and clinical guidelines advocating caution for the use of specific NSAIDs.
Drug utilization study.
Nationwide wholesale statistics and prescription registries in Denmark, Finland, Iceland, Norway, and Sweden (2000-2016).
Our main outcome measures were yearly total sales, expressed as number of sold defined daily doses (DDDs)/1000 inhabitants/day, and yearly prevalence of prescription use, expressed as number of prescription users per 1000 inhabitants. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. Total sales of NSAIDs increased in all countries and were highest in Iceland, with 74.3 DDDs/1000 inhabitants/day sold in 2016, followed by Finland (73.9), Sweden (54.4), Norway (43.8), and Denmark (31.8). Diclofenac use declined after 2008 in all countries but remained the most widely prescribed NSAID in Norway, with 63 prescription users/1000 inhabitants in 2016. Diclofenac sales also remained high in Iceland (12.7 DDD/1000 inhabitants/day), Norway (8.1), and Sweden (7.8). Since its introduction in 2003, the use of etoricoxib, a newer selective COX-2 inhibitor, increased in all countries except Denmark, with highest sales in Finland (6.7 DDD/1000 inhabitants/day in 2016).
Sales and prescription patterns of NSAIDs in the Nordic countries has changed along with the accumulating evidence for the cardiovascular risks of specific NSAIDs. However, given existing evidence on the cardiovascular risks associated with the use of diclofenac and etoricoxib, the persistent high use of diclofenac in Iceland, Norway, and Sweden, the persistent over-the-counter availability of diclofenac in Norway and Sweden, and the increasing use of etoricoxib in most of the Nordic countries pose a cardiovascular health concern.
在过去十年中,非阿司匹林类非甾体抗炎药(NSAIDs),尤其是双氯芬酸和新型选择性环氧化酶(COX)-2 抑制剂的心脏毒性证据不断增加。我们的目的是研究随着特定 NSAIDs 使用的心血管风险的证据、监管声明和临床指南不断增加,北欧国家对 NSAIDs 的使用是否发生了变化。
药物利用研究。
丹麦、芬兰、冰岛、挪威和瑞典的全国批发统计数据和处方登记处(2000-2016 年)。
我们的主要结局指标是每年的总销售额,以每 1000 名居民销售的规定日剂量(DDD)数量表示;以及每年处方使用的流行率,以每 1000 名居民的处方使用者数量表示。DDD 是用于成人主要适应证的药物的平均维持剂量。所有国家的 NSAIDs 总销售额均增加,冰岛最高,2016 年销售 74.3 DDD/1000 名居民/天,其次是芬兰(73.9)、瑞典(54.4)、挪威(43.8)和丹麦(31.8)。2008 年以后,所有国家的双氯芬酸使用量均下降,但在挪威仍是使用最广泛的 NSAID,2016 年有 63 名处方使用者/1000 名居民。双氯芬酸的销售额在冰岛(12.7 DDD/1000 名居民/天)、挪威(8.1)和瑞典(7.8)仍然很高。自 2003 年引入以来,新型选择性 COX-2 抑制剂依托考昔在除丹麦以外的所有国家的使用量都有所增加,2016 年在芬兰的销售额最高(6.7 DDD/1000 名居民/天)。
随着特定 NSAIDs 心血管风险的证据不断增加,北欧国家 NSAIDs 的销售和处方模式发生了变化。然而,鉴于目前关于使用双氯芬酸和依托考昔与心血管风险相关的证据,在冰岛、挪威和瑞典,双氯芬酸的高使用率持续存在,在挪威和瑞典,双氯芬酸仍然可以在非处方购买,在大多数北欧国家,依托考昔的使用量不断增加,这对心血管健康构成了威胁。