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A Pharmacovigilance Study of Adverse Drug Reactions Reported for Cardiovascular Disease Medications Approved Between 2012 and 2017 in the United States Food and Drug Administration Adverse Event Reporting System (FAERS) Database

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Abstract

Purpose

Between 2012 and 2017, the FDA approved 29 therapies for a cardiovascular disease (CVD) indication. Due to the limited literature on patient safety outcomes for recently approved CVD medications, this study investigated adverse drug reports (ADRs) reported in the FDA Adverse Event Reporting System (FAERS).

Methods

A disproportionality analysis of spontaneously reported ADR was conducted. Reports in FAERS from Quarter 1, 2012, through Quarter 1, 2019, were compiled, allowing a 2-year buffer following drug approval in 2017. Top 10 reported ADRs and reporting odds ratios (ROR; confidence interval (CI)), a measure of disproportionality, were analyzed and compared to drugs available prior to 2012 as appropriate.

Results

Of 7,952,147 ADR reports, 95,016 (1.19%) consisted of reports for newly approved CVD medications. For oral anticoagulants, apixaban had significantly lower reports for anemia and renal failure compared to dabigatran and rivaroxaban but greater reports for neurological signs/symptoms, and arrhythmias. Evaluating heart failure drugs, sacubitril/valsartan had greater reports for acute kidney injury, coughing, potassium imbalances, and renal impairment but notably, lower for angioedema compared to lisinopril. Assessing familial hypercholesterolemia drugs, alirocumab had greater reports for joint-related-signs/symptoms compared to other agents in this category. A newer pulmonary arterial hypertension treatment, selexipag, had greater reports of reporting for bone/joint-related-signs/symptoms but riociguat had greater reports for hemorrhages and vascular hypotension.

Conclusion

Pharmacovigilance studies allow an essential opportunity to evaluate the safety profile of CVD medications in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved CVD medications.

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Data Availability

A list of medications approved by the FDA in the USA between 2012 and 2017 was generated through searches on FDA.gov and Drugs.com. Adverse drug reaction reports were gathered via the United States FDA Adverse Event Reporting System (FAERS). This database is publicly available online through the FAERS Public Dashboard.

Code Availability

Statistical analysis was conducted via StataSE® v16.1 (StataCorp, College Station, TX). Medication mentions within FAERS were standardized to RxNorm standard code ingredients and clinical medications forms for multi-ingredient medications using a combination of the National Library of Medicine’s Metamap program, the Usagi tool developed by the Observational Health Data Science and Informatics (OHDSI) collaborative, and manual review. The OHDSI standardized vocabulary was used to map FAERS medications indication and reaction terms from the Medical Dictionary for Regulatory Activities (MedDRA) terminology to Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) standard codes. Code is available upon request.

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Author information

Authors and Affiliations

  1. School of Pharmacy, University of Pittsburgh, 3507 Terrace St., Pittsburgh, PA, 15261, USA

    Niti M. Patel, Britney A. Stottlemyer, Matthew P. Gray, Richard D. Boyce & Sandra L. Kane-Gill

  2. Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA

    Richard D. Boyce

Authors
  1. Niti M. Patel
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  2. Britney A. Stottlemyer
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  3. Matthew P. Gray
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  4. Richard D. Boyce
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  5. Sandra L. Kane-Gill
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Contributions

• Literature search—Niti Patel, Britney Stottlemeyer

• Data collection—Richard D. Boyce, Matthew P. Gray, Britney A. Stottlemyer

• Study design—Sandra L. Kane-Gill, Matthew P. Gray, Niti Patel, Britney Stottlemeyer, Richard D. Boyce

• Analysis of data—Niti Patel, Britney Stottlemeyer, Matthew P. Gray

• Manuscript preparation—Sandra L. Kane-Gill, Niti Patel, Britney Stottlemeyer

• Review of manuscript—Richard D. Boyce, Matthew P. Gray

Corresponding author

Correspondence to Sandra L. Kane-Gill.

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Patel, N.M., Stottlemyer, B.A., Gray, M.P. et al. A Pharmacovigilance Study of Adverse Drug Reactions Reported for Cardiovascular Disease Medications Approved Between 2012 and 2017 in the United States Food and Drug Administration Adverse Event Reporting System (FAERS) Database. Cardiovasc Drugs Ther 36, 309–322 (2022). https://doi.org/10.1007/s10557-021-07157-3

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