A Retrospective Cohort Study of the 2018 Angiotensin Receptor Blocker Recalls and Subsequent Drug Shortages in Patients With Hypertension

Abstract

Background: Valsartan was recalled by the US Food and Drug Administration in July 2018 for carcinogenic impurities, resulting in a drug shortage and management challenges for valsartan users. The influence of the valsartan recall on clinical outcomes is unknown. We compared the risk of adverse events between hypertensive patients using valsartan and a propensity score-matched group using nonrecalled angiotensin receptor blockers and angiotensin-converting enzyme inhibitors.

Methods and results: We used Optum's deidentified Clinformatics Datamart (July 2017-January 2019). Hypertensive patients who received valsartan or nonrecalled angiotensin receptor blockers/angiotensin-converting enzyme inhibitors for 1 year before and on the recall date were compared. Primary outcomes were measured in the 6 months following the recall and included: (1) a composite measure of all-cause hospitalization, all-cause emergency department visit, and all-cause urgent care visit, and (2) a composite cardiac event measure of hospitalizations for acute myocardial infarction and hospitalizations/emergency department visits/urgent care visits for stroke/transient ischemic attack, heart failure, or hypertension. We compared the risk of outcomes between treatment groups using Cox proportional hazard models. Of the hypertensive patients, 76 934 received valsartan, and 509 472 received a nonrecalled angiotensin receptor blocker/angiotensin-converting enzyme inhibitor. Valsartan use at the time of recall was associated with a higher risk of all-cause hospitalization, emergency department use, or urgent care use (hazard ratio [HR], 1.02 [95% CI, 1.00-1.04]) and the composite of cardiac events (HR, 1.22 [95% CI, 1.15-1.29]) within 6 months after the recall.

Conclusions: The valsartan recall and shortage affected hypertensive patients. Local- and national-level systems need to be enhanced to protect patients from drug shortages by providing safe and reliable medication alternatives.

Keywords: drug recall; drug shortages; hypertension; valsartan.

Figure 1. Cohort assignment for patients with hypertension taking angiotensin receptor blockers (ARBs)/angiotensin‐converting enzyme inhibitors (ACE‐Is) affected by a valsartan recall (exposed group) and those who did not experience a recall (unexposed group).

Consolidated Standards of Reporting Trials flow diagram to show construction of the study cohort and inclusion and exclusion criteria for the exposed group (valsartan) and unexposed group (receiving nonrecalled ARB and ACE‐I). Index date was defined as the date the US Food and Drug Administration issued the valsartan recall (July 13, 2018).