Changes in blood pressure, medication adherence, and cardiovascular-related health care use associated with the 2018 angiotensin receptor blocker recalls and drug shortages among patients with hypertension.

IF 2.3 4区 医学 Q2 HEALTH CARE SCIENCES & SERVICES
Katherine Callaway Kim, Eric T Roberts, Julie M Donohue, Chester B Good, Lindsay M Sabik, Joshua W Devine, Mina Tadrous, Katie J Suda
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引用次数: 0

Abstract

Background: One of the largest-ever retail drug shortages began in 2018 when several angiotensin II receptor blockers (ARBs) for treating hypertension, heart failure, and chronic kidney disease-valsartan, losartan, and irbesartan-were recalled for carcinogenic impurities. The long-term consequences of the ARB shortages and whether certain groups experienced more adverse outcomes is unknown.

Objective: To evaluate changes in adherence and health outcomes after ARB recalls and to identify patients who experienced greater changes in access and adverse clinical outcomes.

Methods: Using an integrated claims and electronic health record dataset and a difference-in-differences design, we evaluated changes in the proportion of days covered (PDC) for ARBs and similar drugs (angiotensin-converting enzyme inhibitors [ACE-Is]), uncontrolled blood pressure, major cardiovascular event (MACE)-related acute care visits, and all-cause ambulatory care visits in the 12 months before vs 18 months after recalls for valsartan, losartan, and irbesartan users vs patients taking similar, nonrecalled drugs (ACE-Is, nonrecalled ARBs). Triple-difference models characterized heterogeneous associations by pre-recall patient demographic (race, ethnicity, age), clinical (baseline indication, mental health conditions), and adherence variables.

Results: Adjusting for pre-recall patient characteristics, we observed no significant changes in PDC for ARBs and ACE-Is (combined), uncontrolled blood pressure, or ambulatory care visits among 86,507 recalled ARB users vs 123,583 comparison drug users in the 18 months after the recalls. Following the recalls, medication switches increased on average by an additional 2.08 percentage points (p.p.) per quarter (95% CI = 2.01-2.15) for recalled ARB vs comparison drug users, a 195.9% relative increase. We observed the most switches in the 90-day period immediately after valsartan's recall (difference-in-difference: 9.48 p.p.; 95% CI = 9.36-9.59; relative change = 892%). Cumulatively, 55.2% of valsartan, 7.6% of losartan, and 18.9% of irbesartan users switched medications after 18 months. We observed an increase in the proportion of recalled ARB vs comparison patients who experienced medication gaps exceeding 30 days (1.13 p.p. per quarter on average; 95% CI = 0.97-1.30), which was most apparent after approximately 15 months (5 quarters). Although MACE-related acute care visits did not change in the quarter (90 days) immediately after valsartan's recall, we observed an increase of 1.40 additional visits per 1,000 recalled ARB vs comparison drug patients in each subsequent quarter, a 9.3% relative increase. Results were similar across most subgroups.

Conclusions: The 2018 ARB recalls were associated with immediate changes in antihypertension medication use. Many patients transitioned to alternative medications. Although overall impacts on clinical outcomes were minimal and not statistically significant, small increases in medication gaps and MACE-related acute care visits among some patients occurred after more than 1 year. The ARB recalls may have been associated with fewer adverse events than other recent shortages owing to the widespread availability of alternative treatments in the same or similar drug class.

高血压患者2018年血管紧张素受体阻滞剂召回和药物短缺相关的血压、药物依从性和心血管相关医疗保健使用的变化
背景:有史以来最大的零售药物短缺之一始于2018年,当时几种用于治疗高血压、心力衰竭和慢性肾病的血管紧张素II受体阻滞剂(arb)缬沙坦、氯沙坦和厄贝沙坦因致癌杂质被召回。ARB短缺的长期后果以及某些群体是否经历了更多的不良后果尚不清楚。目的:评估ARB召回后依从性和健康结果的变化,并确定在可及性和不良临床结果方面经历较大变化的患者。方法:使用综合索赔和电子健康记录数据集和差异中的差异设计,我们评估了缬沙坦、氯沙坦和阿贝沙坦使用者与服用类似药物的患者在召回前12个月与召回后18个月之间,arb和类似药物(血管紧张素转换酶抑制剂[ACE-Is])的覆盖天数(PDC)比例、未控制血压、主要心血管事件(MACE)相关的急性护理就诊和全因门诊就诊的变化。非召回药物(ACE-Is,非召回arb)。三差模型通过回忆前患者人口统计学(种族、民族、年龄)、临床(基线适应症、精神健康状况)和依从性变量表征异质性关联。结果:调整召回前的患者特征,我们观察到在召回后的18个月内,86,507名被召回的ARB使用者与123,583名对照药物使用者相比,ARB和ACE-Is(联合)的PDC、未控制的血压或门诊就诊没有显著变化。在召回之后,与对照药物使用者相比,被召回ARB的药物转换平均每季度增加2.08个百分点(95% CI = 2.01-2.15),相对增加195.9%。在缬沙坦召回后的90天内,我们观察到最多的变化(差中差:9.48 p.p.;95% ci = 9.36-9.59;相对变化= 892%)。累积起来,55.2%的缬沙坦、7.6%的氯沙坦和18.9%的厄贝沙坦使用者在18个月后更换了药物。我们观察到,与经历药物间隔超过30天的对照患者相比,召回ARB的比例有所增加(平均每季度1.13次;95% CI = 0.97-1.30),在大约15个月(5个季度)后最为明显。尽管在缬沙坦召回后的第一个季度(90天),与mace相关的急性护理就诊没有变化,但我们观察到,在随后的每个季度中,每1000名被召回的ARB患者与对照药物患者的就诊次数增加了1.40次,相对增加了9.3%。大多数亚组的结果相似。结论:2018年ARB召回与抗高血压药物使用的即时变化有关。许多患者转而使用替代药物。尽管对临床结果的总体影响很小且无统计学意义,但在1年多后,一些患者的药物缺口和与mace相关的急性护理就诊数出现了小幅增加。由于相同或类似药物类别的替代治疗的广泛可用性,ARB召回与近期其他短缺相比,可能与较少的不良事件有关。
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来源期刊
Journal of managed care & specialty pharmacy
Journal of managed care & specialty pharmacy Health Professions-Pharmacy
CiteScore
3.50
自引率
4.80%
发文量
131
期刊介绍: JMCP welcomes research studies conducted outside of the United States that are relevant to our readership. Our audience is primarily concerned with designing policies of formulary coverage, health benefit design, and pharmaceutical programs that are based on evidence from large populations of people. Studies of pharmacist interventions conducted outside the United States that have already been extensively studied within the United States and studies of small sample sizes in non-managed care environments outside of the United States (e.g., hospitals or community pharmacies) are generally of low interest to our readership. However, studies of health outcomes and costs assessed in large populations that provide evidence for formulary coverage, health benefit design, and pharmaceutical programs are of high interest to JMCP’s readership.
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