What is the clinical evidence from this study?

Study design: Observational. Population: Colorectal cancer / adverse drug reactions. Intervention: Capecitabine vs. Other colorectal cancer drugs (5-FU, irinotecan, oxaliplatin, bevacizumab, panitumumab). Primary outcome: Cardiac arrhythmias (vs irinotecan) (ROR 1.2971, 95% CI 1.0196-1.6502).

November 16, 2024Open Access

The Descriptive and Disproportionality Assessment of EudraVigilance Database Reports on Capecitabine Induced Cardiotoxicity

RVRazvan Constantin VonicaLucian Blaga University of Sibiu ABAnca ButucăLucian Blaga University of Sibiu AVAndreea Loredana Vonica-ȚincuLucian Blaga University of Sibiu

Key Result

Capecitabine exposure was associated with a higher probability of reported cardiac arrhythmias compared to irinotecan (ROR 1.2971; 95% CI 1.0196-1.6502).

Study Design

Type

Observational

Structured PICO

Does capecitabine have a higher risk of cardiac toxicity compared to other colorectal cancer drugs?

Population

Retrospective pharmacovigilance study of adverse drug reaction reports submitted to the EudraVigilance database until July 2024 to assess the cardiac toxicity of capecitabine.

Exposure

Capecitabine

Comparator

5-fluorouracil, irinotecan, oxaliplatin, bevacizumab, and panitumumab

Outcome

Cardiac adverse drug reactions (including myocardial infarction, heart failure, arrhythmias, and cardiomyopathies)safety

Capecitabine is associated with significant cardiac adverse events, comparable to 5-FU, highlighting the need for rigorous cardiovascular monitoring in treated patients.

Main Result

Odds Ratio: 1.2971 (95% CI 1.0196–1.6502)

Abstract

Capecitabine (CAP) is one of the most commonly prescribed fluoropyrimidines in oncology, especially in the treatment of colon cancer. Cardiac toxicity is a severe and potentially lethal adverse drug reaction (ADR) against fluoropyrimidines. Cardiac ADRs, such as myocardial infarction (MI), heart failure (HF), arrhythmias, and a number of cardiomyopathies, are reported for these molecules. To have a better understanding of the risk-benefit ratio of colon cancer therapy, a pharmacovigilance study of real-world evidence of the cardiac toxicity of antineoplastic agents is required. AIM: This post-marketing research on CAP aims to assess the risk of cardiac toxicity. Five other antitumor drugs used in colorectal cancer, i.e., 5-fluorouracil (5-FU), irinotecan (IRI), oxaliplatin (OX), bevacizumab (BEV) and panitumumab (PAN), were also studied to create a relative profile of observed cardiotoxicity. METHODS: A retrospective study based on reports submitted in the EudraVigilance (EV) database until 28 July 2024 was conducted. Using the aggregated data from EV, a descriptive analysis and disproportionality analysis of cardiac ADRs induced by fluoropyrimidines were performed. To evaluate the disproportionality of the signals, Reporting Odds Ratio (ROR) and 95% confidence interval (95% CI) were calculated by comparison with other drugs used in colorectal cancer: 5-FU, IRI, OX, BEV, and PAN. RESULTS: "Cardiac disorders" represent 3.4% of the total reports for CAP. The value is comparable to 5-FU, but higher than for other drugs. t was observed that there are no significant differences in the occurrence of cardiac ADRs in patients exposed to CAP and 5-FU treatments, and in particular MI and HF. Compared to 5-FU, which could produce cardiac arrythmias with a higher probability than all other drugs, CAP has a higher probability of reporting this ADR only in comparison with IRI (ROR: 1.2971; 95% CI: 1.0196-1.6502). CONCLUSIONS: CAP induces adverse cardiovascular reactions, especially MI, HF, and cardiomyopathies. Arrhythmias have been shown to be side effects more frequent associated with 5-FU than with CAP. The results emphasize the need for a rigorous cardiovascular monitoring of patients following treatment with CAP or 5-FU and especially for those with pre-existing cardiac pathology.

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