Thromboembolic Risk of C1 Esterase Inhibitors: A Systematic Review on Current Evidence

ABSTRACT

Introduction

The exact risk of developing a thromboembolic event (TEE) while using complement 1 esterase inhibitors (C1-INHs) is currently undetermined for patients with hereditary angioedema (HAE). This systematic review aimed to define the potential risk of TEEs from these agents.

Areas covered

This evaluation covers publications examining or mentioning the risk of TEEs in association with C1-INHs. A systematic literature search was conducted utilizing PubMed, Scopus, and ProQuest. This review utilized search results through January 2020 and followed the PRISMA recommendations for a systematic review. Articles not available in English and animal or in-vitro studies were excluded. For inclusion, studies had to be open-label, randomized-controlled, cross-sectional, or clinical observational studies. A total of 13 studies met inclusion criteria and yielded 1716 patients receiving at least one dose of C1-INH, though only 41 incidences of thrombosis were documented.

Expert opinion

Significant heterogeneity exists in the available literature concerning both study design and the reporting of data; therefore, interpretation of thrombotic risk is difficult. TEEs are rarely reported in the literature, and they seem unlikely to occur in patients without underlying risk factors. Important risk factors include those found in the prescribing information of C1-INHs.

KEYWORDS:

• C1 esterase inhibitors
• hereditary angioedema
• embolism and thrombosis
• review
• systematic
• clinical pharmacy services

Article highlights

• Brief, yet thorough, introduction of hereditary angioedema and the clinical role of C1 esterase inhibitors

• Summary of pertinent pharmacology and mechanism of action of C1 esterase inhibitors

• Hypothesized mechanisms of thrombosis associated with C1 esterase inhibitors

• Systematic review of clinical trials and cases that describe risk factors and incidences of thrombotic events associated with C1 esterase inhibitors

• Readily available tables and figures for use by clinicians at the bedside to help determine patient risk of thrombosis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.