High-Throughput Screening for Prescribing Cascades Among Real-World Angiotensin-Converting Enzyme Inhibitor Initiators.

IF 2.4 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacoepidemiology and Drug Safety Pub Date : 2025-03-01 DOI:10.1002/pds.70132

Asinamai M Ndai, Kayla Smith, Shailina Keshwani, Jaeyoung Choi, Michael Luvera, Julia Hunter, Rebecca Galvan, Tanner Beachy, Matt Molk, Shannon Wright, Marianna Calvet, Carl J Pepine, Stephan Schmidt, Scott M Vouri, Earl J Morris, Steven M Smith

{"title":"High-Throughput Screening for Prescribing Cascades Among Real-World Angiotensin-Converting Enzyme Inhibitor Initiators.","authors":"Asinamai M Ndai, Kayla Smith, Shailina Keshwani, Jaeyoung Choi, Michael Luvera, Julia Hunter, Rebecca Galvan, Tanner Beachy, Matt Molk, Shannon Wright, Marianna Calvet, Carl J Pepine, Stephan Schmidt, Scott M Vouri, Earl J Morris, Steven M Smith","doi":"10.1002/pds.70132","DOIUrl":null,"url":null,"abstract":"Purpose: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly prescribed, but their adverse effects may prompt new drug prescription(s), known as prescribing cascades (PCs). We aimed to identify potential ACEI-induced PCs using high-throughput sequence symmetry analysis.Methods: Using claims data from a national sample of Medicare beneficiaries (2011-2020), we identified new ACEI users aged ≥ 66 years with continuous enrollment ≥ 360 days before and ≥ 180 days after ACEI initiation. We screened for initiation of 446 other (non-antihypertensive) \"marker\" drug classes within ±90 days of ACEI initiation, generating sequence ratios (SRs) reflecting proportions of ACEI users starting the marker class after versus before ACEI initiation. Adjusted SRs (aSRs) accounted for prescribing trends over time. For significant aSRs, we calculated the naturalistic number needed to harm (NNTH), and significant signals underwent clinical review for plausibility.Results: We identified 308 579 ACEI initiators (mean age 76.1 ± 7.5 years; 59.6% female; 88.6% with hypertension). Of 446 marker classes evaluated, 81 signals were significant, and 42 (52%) classified as potential PCs after clinical review. The strongest signals ranked by lowest NNTH included corticosteroids (NNTH 313; 95% CI, 262-392) and serotonin type 3 (5-HT3) antagonists (NNTH 496; 95% CI, 392-689); the strongest signals ranked by highest aSR included sympathomimetics (aSR, 1.97; 95% CI, 1.10-3.53) and other antianemic preparations (aSR, 1.87; 95% CI, 1.31-2.67).Conclusion: Identified prescribing cascade signals were indicative of known and possibly underrecognized ACEI adverse events in this Medicare cohort. The findings are hypothesis-generating and require further investigation to determine the extent and impact of the identified PCs on health outcomes.","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 3","pages":"e70132"},"PeriodicalIF":2.4000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067835/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacoepidemiology and Drug Safety","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/pds.70132","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly prescribed, but their adverse effects may prompt new drug prescription(s), known as prescribing cascades (PCs). We aimed to identify potential ACEI-induced PCs using high-throughput sequence symmetry analysis.

Methods: Using claims data from a national sample of Medicare beneficiaries (2011-2020), we identified new ACEI users aged ≥ 66 years with continuous enrollment ≥ 360 days before and ≥ 180 days after ACEI initiation. We screened for initiation of 446 other (non-antihypertensive) "marker" drug classes within ±90 days of ACEI initiation, generating sequence ratios (SRs) reflecting proportions of ACEI users starting the marker class after versus before ACEI initiation. Adjusted SRs (aSRs) accounted for prescribing trends over time. For significant aSRs, we calculated the naturalistic number needed to harm (NNTH), and significant signals underwent clinical review for plausibility.

Results: We identified 308 579 ACEI initiators (mean age 76.1 ± 7.5 years; 59.6% female; 88.6% with hypertension). Of 446 marker classes evaluated, 81 signals were significant, and 42 (52%) classified as potential PCs after clinical review. The strongest signals ranked by lowest NNTH included corticosteroids (NNTH 313; 95% CI, 262-392) and serotonin type 3 (5-HT₃) antagonists (NNTH 496; 95% CI, 392-689); the strongest signals ranked by highest aSR included sympathomimetics (aSR, 1.97; 95% CI, 1.10-3.53) and other antianemic preparations (aSR, 1.87; 95% CI, 1.31-2.67).

Conclusion: Identified prescribing cascade signals were indicative of known and possibly underrecognized ACEI adverse events in this Medicare cohort. The findings are hypothesis-generating and require further investigation to determine the extent and impact of the identified PCs on health outcomes.

查看原文本刊更多论文

高通量筛选处方级联在现实世界中的血管紧张素转换酶抑制剂的启动。

目的：血管紧张素转换酶抑制剂（acei）是常用的处方，但其不良反应可能会促使新的药物处方，称为处方级联反应（PCs）。我们的目的是通过高通量序列对称分析来识别潜在的acei诱导的pc。方法：使用来自全国医疗保险受益人样本（2011-2020年）的索赔数据，我们确定了年龄≥66岁的ACEI新用户，ACEI开始前≥360天，开始后≥180天。我们筛选了446例其他（非抗高血压）药物的起始治疗在ACEI启动后±90天内的“标记”药物类别，生成序列比率（SRs），反映ACEI用户在启动后与启动前开始标记类别的比例。调整后的SRs （aSRs）反映了随时间推移的处方趋势。对于严重的asr，我们计算了造成伤害所需的自然数量（NNTH），并对显著信号进行了临床评估以确定其合理性。结果：我们确定了308 579例ACEI启动者(平均年龄76.1±7.5岁；59.6%的女性;88.6%患有高血压)。在评估的446个标志物类别中，81个信号显著，42个（52%）在临床审查后被归类为潜在的PCs。按最低NNTH排列的最强信号包括皮质类固醇(NNTH 313；95% CI, 262-392)和3型血清素（5-HT3）拮抗剂(NNTH 496；95% ci, 392-689)；aSR最高的最强信号包括拟交感神经(aSR, 1.97；95% CI, 1.10-3.53)和其他抗贫血制剂(aSR, 1.87；95% ci, 1.31-2.67)。结论：确定的处方级联信号指示已知的和可能未被充分认识的ACEI不良事件。这些发现是假设，需要进一步调查以确定已确定的pc对健康结果的程度和影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pharmacoepidemiology and Drug Safety 医学-药学

CiteScore

4.80

自引率

7.70%

发文量

173

审稿时长

3 months

期刊介绍： The aim of Pharmacoepidemiology and Drug Safety is to provide an international forum for the communication and evaluation of data, methods and opinion in the discipline of pharmacoepidemiology. The Journal publishes peer-reviewed reports of original research, invited reviews and a variety of guest editorials and commentaries embracing scientific, medical, statistical, legal and economic aspects of pharmacoepidemiology and post-marketing surveillance of drug safety. Appropriate material in these categories may also be considered for publication as a Brief Report. Particular areas of interest include: design, analysis, results, and interpretation of studies looking at the benefit or safety of specific pharmaceuticals, biologics, or medical devices, including studies in pharmacovigilance, postmarketing surveillance, pharmacoeconomics, patient safety, molecular pharmacoepidemiology, or any other study within the broad field of pharmacoepidemiology; comparative effectiveness research relating to pharmaceuticals, biologics, and medical devices. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, as these methods are truly used in the real world; methodologic contributions of relevance to pharmacoepidemiology, whether original contributions, reviews of existing methods, or tutorials for how to apply the methods of pharmacoepidemiology; assessments of harm versus benefit in drug therapy; patterns of drug utilization; relationships between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines; evaluations of risk management plans and programmes relating to pharmaceuticals, biologics and medical devices.