School of Pharmacy, University of Pittsburgh, 3507 Terrace St., Pittsburgh, PA, 15261, USA.
Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA.
Cardiovasc Drugs Ther. 2022 Apr;36(2):309-322. doi: 10.1007/s10557-021-07157-3. Epub 2021 Feb 18.
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).
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.
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.
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.
在 2012 年至 2017 年间，FDA 批准了 29 种治疗心血管疾病（CVD）适应证的疗法。由于最近批准的 CVD 药物的患者安全结果的文献有限，本研究调查了 FDA 不良事件报告系统（FAERS）中报告的不良药物报告（ADR）。
对自发报告的 ADR 进行了不相称性分析。从 2012 年第一季度到 2019 年第一季度，编译了 FAERS 中的报告，允许在 2017 年药物批准后有 2 年的缓冲期。分析并比较了报告的前 10 种 ADR 和报告比值比（ROR；置信区间（CI）），这是一种衡量不相称性的指标，并与 2012 年之前的药物进行了适当比较。
在 7952147 份 ADR 报告中，95016（1.19%）由新批准的 CVD 药物的报告组成。对于口服抗凝剂，与达比加群和利伐沙班相比，阿哌沙班的贫血和肾衰竭报告明显较少，但神经系统症状/体征和心律失常的报告较多。评估心力衰竭药物时，沙库比曲/缬沙坦的急性肾损伤、咳嗽、钾失衡和肾功能不全报告较多，但血管性水肿报告明显低于赖诺普利。评估家族性高胆固醇血症药物时，阿利罗库单抗的关节相关症状/体征报告较多，而该类别中的其他药物报告较少。一种新型肺动脉高压治疗药物塞利西帕格的报告中，骨骼/关节相关症状/体征的报告较多，但 riociguat 的出血和血管性低血压报告较多。
药物警戒研究为评估 CVD 药物在临床实践中的安全性概况提供了一个重要机会。需要进一步研究来评估最近批准的 CVD 药物的这些报告的安全问题。
