Cardiovascular Adverse Events Associated with Prostate Cancer Treatment: A Disproportionality Analysis from the Food and Drug Administration Adverse Event Reporting System Database
Department of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
Pharmacoepidemiology 2024, 3(4), 373-382; https://doi.org/10.3390/pharma3040026
Submission received: 19 October 2024
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Revised: 23 November 2024
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Accepted: 25 November 2024
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Published: 27 November 2024
(This article belongs to the Topic Advance in Cancer Pharmacoepidemiology)
Abstract
:Background/Objectives: Several drugs used to treat prostate cancer have been reported to cause cardiovascular adverse events, and this study sought to identify the real-world risk. Methods: This study utilized real-world data from the FAERS to analyze the association between prostate cancer treatment and cardiovascular adverse events. It evaluated men treated with LHRH agonists and antagonists, antiandrogens, androgen synthesis inhibitors, and PARP inhibitors from 2003 to 2023. This study included patients treated with leuprolide, goserelin, triptorelin, degarelix, relugolix, bicalutamide, flutamide, apalutamide, nilutamide, abiraterone, enzalutamide, olaparib, rucaparib, talazoparib, and niraparib. The main outcome measure was the reported odds ratio (ROR) of adverse cardiovascular event associated with these treatments. Results: Among the 4,049,329 unique adverse event reports, 4391 cardiovascular events were identified. Leuprolide (ROR 0.481, 95% CI: 0.423–0.547), triptorelin (ROR 0.527, 95% CI: 0.305–0.909), enzalutamide (ROR 0.393, 95% CI: 0.341–0.452), and olaparib (ROR 0.145, 95% CI: 0.054–0.386) reduced the risk of myocardial infarction. Goserelin increased the risk of myocardial infarction (ROR 2.235, 95% CI: 1.367–3.654). Degarelix and relugolix both increased the risk of heart failure (ROR 3.136, 95% CI: 2.186–4.497), and enzalutamide was associated with an increased risk of heart failure (ROR 1.305, 95% CI: 1.135–1.501). Bicalutamide increased the risk of unstable angina (ROR 3.019, 95% CI: 1.621–5.622) and heart failure (ROR 3.730, 95% CI: 3.085–4.510). Niraparib increased the risk of hypertension (ROR 4.154, 95% CI: 1.709–10.092). Conclusions: These findings underscore the need for clinicians to monitor cardiac complications in patients undergoing these therapies.
1. Introduction
Prostate cancer is the most prevalent cancer in men; however, early detection and effective treatments result in a 5-year survival rate for prostate cancer of nearly 100% [1,2]. A significant proportion of men diagnosed with this disease have pre-existing cardiovascular comorbidities. Conditions such as hypertension, coronary artery disease, atrial fibrillation, and heart failure are particularly common in this patient population, and the presence of these comorbidities complicates prostate cancer management, as it may increase vulnerability to therapy-induced adverse events and heighten overall morbidity and mortality [3]. Therefore, it is essential to thoroughly understand the cardiovascular adverse events (AEs) associated with the treatment of this disease. Fortunately, there are many therapies available for men with prostate cancer, including luteinizing hormone-releasing hormone (LHRH) agonists and antagonists, antiandrogens, androgen synthesis inhibitors, and poly-ADP ribose polymerase (PARP) inhibitors [4]. However, studies have shown that these drugs are associated with cardiovascular adverse events (AE) [5,6]. This study focuses on identifying the specific cardiovascular complications associated with prostate cancer therapies by analyzing data from the FDA Adverse Events Reporting System (FAERS) database. This comprehensive, real-world dataset offers valuable insights into AE patterns, allowing clinicians to make informed decisions about treatment risks. By elucidating the cardiovascular AEs associated with each therapy, this study aims to equip healthcare providers with critical information, enhancing their ability to balance cancer treatment efficacy with cardiovascular safety.
2. Results
2.1. Luteinizing Hormone-Releasing Hormone Agonists and Antagonists
Leuprolide was associated with a significantly reduced risk of myocardial infarction (ROR 0.481, 95% CI: 0.423–0.547) and coronary artery disease (ROR 0.572, 95% CI: 0.435–0.754), whereas goserelin increased the risk of myocardial infarction (ROR 2.235, 95% CI, 1.367–3.654) and coronary artery disease (ROR 1.876, 95% CI: 1.148–3.067) (Table 1). Triptorelin also reduced the risk of myocardial infarction (ROR 0.527, 95% CI, 0.305–0.909). Degarelix and relugolix were associated with a higher risk of heart failure (ROR 3.136, 95% CI: 2.186–4.497). Leuprolide was associated with a lower risk of atrial fibrillation (ROR 0.789, 95% CI, 0.670–0.929), whereas goserelin significantly increased this risk (ROR 2.513, 95% CI, 1.866–3.385). Goserelin also showed a significantly higher risk of atrial flutter (ROR 5.347, 95% CI, 2.775–10.300) and dilated cardiomyopathy (ROR 7.388, 95% CI, 2.689–20.299). Degarelix and relugolix significantly increased the risk of mitral valve disease (ROR 3.377, 95% CI: 1.265–9.015) and tricuspid valve disease (ROR 3.807; 95% CI, 1.225–11.827). Leuprolide reduced the risk of pericarditis (ROR 0.243, 95% CI, 0.091–0.647) and pericardial effusion (ROR 0.422, 95% CI, 0.258–0.689). Goserelin increased the risk of complete AV block (ROR 3.067, 95% CI, 1.149–8.186), and triptorelin showed an even higher risk for this condition (ROR 4.408, 95% CI, 1.419–13.696). Finally, leuprolide and goserelin were associated with a lower risk of cardiac arrest (ROR 0.503, 95% CI, 0.407–0.622 and ROR 0.487, 95% CI, 0.243–0.975, respectively).
2.2. Antiandrogens and Androgen Synthesis Inhibitors
Enzalutamide significantly reduced the risk of myocardial infarction (ROR 0.393, 95% CI: 0.341–0.452), coronary artery disease (ROR 0.394, 95% CI: 0.282–0.549), angina pectoris (ROR 0.374, 95% CI: 0.248–0.563), and unstable angina (ROR 0.173, 95% CI: 0.056–0.536) (Table 2). However, it increased the risk of heart failure (ROR 1.305, 95% CI, 1.135–1.501), hypertension (ROR 1.878, 95% CI, 1.698–2.076), bradycardia (ROR 0.334, 95% CI, 0.241–0.463), pericarditis (ROR 0.183, 95% CI, 0.059–0.567), and myocarditis (ROR 0.273, 95% CI, 0.122–0.608). Bicalutamide increased the risk of unstable angina (ROR 3.019, 95% CI: 1.621–5.622), heart failure (ROR 3.730, 95% CI: 3.085–4.510), atrial fibrillation (ROR 1.538, 95% CI: 1.176–2.011), atrial flutter (ROR 2.975, 95% CI: 1.597–5.540), ventricular fibrillation (ROR 3.122, 95% CI: 1.845–5.281), and dilated cardiomyopathy (ROR 38.702, 95% CI: 14.083–106.359). It also increased the risk of aortic valve disease (ROR 2.776, 95% CI, 1.039–7.417), first-degree AV block (ROR 3.698, 95% CI, 1.657–8.255), and complete AV block (ROR 2.694, 95% CI, 1.282–5.662). Apalutamide showed an increased risk of hypertension (ROR 2.371, 95% CI, 1.962–2.864), bradycardia (ROR 0.306, 95% CI, 0.127–0.736), and complete AV block (ROR 4.408, 95% CI, 1.419–13.696). Flutamide significantly increased the risk of heart failure (ROR 4.215, 95% CI, 2.179–8.152). Abiraterone increased the risk of heart failure (ROR 1.440, 95% CI, 1.236–1.678), hypertension (ROR 1.837, 95% CI, 1.669–2.023), atrial fibrillation (ROR 1.448, 95% CI, 1.258–1.665), and cardiac arrest (ROR 0.388, 95% CI, 0.294–0.512). It also showed a reduced risk of coronary artery disease (ROR 0.208, 95% CI, 0.123–0.351), angina pectoris (ROR 0.560, 95% CI, 0.381–0.823), and unstable angina (ROR 0.229, 95% CI, 0.074–0.710). Lastly, no cardiac AEs were noted with nilutamide in this study.
2.3. PARP Inhibitors
Olaparib significantly reduced the risk of myocardial infarction (ROR 0.145, 95% CI, 0.054–0.386) (Table 3). Niraparib displayed a significantly increased risk of hypertension (ROR 4.154, 95% CI: 1.709–10.092) and atrial flutter, which was demonstrated to be a significant concern (ROR 31.564, 95% CI: 10.080–98.837).
3. Discussion
The cardiovascular risk profiles associated with LHRH agonists and antagonists, antiandrogens, androgen synthesis inhibitors, and PARP inhibitors highlight the need for careful consideration in clinical practice. Variations in cardiovascular outcomes necessitate a nuanced approach to treatment selection, especially in patients with pre-existing cardiovascular conditions or those at an elevated risk for such events.
This study revealed varied cardiovascular effects of hormone therapies and targeted treatments. The LHRH agonist leuprolide appears beneficial, lowering the risks of MI, CAD, atrial fibrillation, and pericardial conditions, while goserelin increases the risks for MI, CAD, atrial arrhythmias, and cardiomyopathy. Triptorelin reduces MI risk but heightens AV block risk, and both degarelix and relugolix are linked to higher heart failure and valve disease risks. Among the antiandrogens, enzalutamide lowers MI, CAD, and angina risks but raises the risks of heart failure and hypertension. In contrast, bicalutamide is associated with heightened risks of multiple serious cardiac events, including atrial fibrillation, heart failure, and valve diseases. The PARP inhibitor olaparib shows a reduced MI risk, while niraparib significantly raises hypertension and atrial flutter risks. These findings highlight distinct cardiovascular profiles across therapies, underscoring the need for tailored cardiovascular risk assessments in treatment planning.
Despite research showing that LHRH antagonists have more positive cardiovascular outcomes than their agonist counterparts, leuprolide demonstrated a favorable cardiovascular risk profile [7]. The drug is associated with a reduced risk of myocardial infarction, coronary artery disease, atrial fibrillation, pericarditis, and pericardial effusion. The data suggest that it may offer cardioprotective benefits, making it a suitable option for patients with or at risk of cardiovascular disease. In stark contrast, goserelin is linked to an increased risk of myocardial infarction, coronary artery disease, atrial fibrillation, atrial flutter, dilated cardiomyopathy, and complete AV block. Despite these risks, goserelin is associated with a lower risk of cardiac arrest, suggesting a complex interplay of cardiovascular effects that warrants further investigation. Triptorelin exhibits a mixed cardiovascular profile, with a reduced risk of myocardial infarction but an increased risk of complete AV block. A recent real-world study found little difference in the rates of these events, with incidences of 5%, 7%, and 5% for leuprolide, goserelin, and triptorelin, respectively [5]. Furthermore, a 2020 meta-analysis found that LHRH agonists have strong positive associations with cardiovascular death, cardiovascular disease, myocardial infarction, and stroke [8]. Further research is needed to determine the mechanism behind LHRH-agonist-induced cardiotoxicity.
LHRH antagonists such as degarelix and relugolix show higher risks of heart failure and valvular diseases, including mitral and tricuspid diseases. Interestingly, this contradicts multiple studies that have shown a lower risk of heart failure in LHRH-antagonist-treated patients than in agonist cohorts [9,10,11]. The PRONOUNCE trial investigating cardiac AEs following degarelix and leuprolide found no differences between the two agents [12]. No reports of valvular disease were found; thus, this leaves an opportunity for further research, especially with respect to the specificity toward the tricuspid valve.
Enzalutamide demonstrates a favorable cardiovascular profile in terms of reducing the risks of myocardial infarction, coronary artery disease, angina pectoris, and unstable angina. However, it also increases the risks of heart failure, hypertension, bradycardia, pericarditis, and myocarditis. A recent meta-analysis corroborates these findings, reporting an increased risk of hypertension with the use of this agent [13]. Hypertension was also common in the PROSPER trial, occurring in 12% of patients [14]. Interestingly, a recent study of the adverse events for enzalutamide and abiraterone did not specifically investigate hypertension or heart failure, potentially missing a strong signal, as seen in this study [15]. This combination of reduced ischemic risk but increased hemodynamic and inflammatory risk suggests that enzalutamide should be prescribed with careful monitoring, particularly in patients susceptible to heart failure and hypertension.
Bicalutamide is associated with significant cardiovascular risks including unstable angina, heart failure, various arrhythmias, and conduction abnormalities. These high-risk ratios necessitate a cautious approach when considering bicalutamide, particularly for patients with any form of cardiovascular vulnerability. However, when looking into the literature, bicalutamide appears to have a relatively safe cardiovascular outcome, aside from a case report of therapy-induced heart failure, including the results from the TERRAIN study [16,17,18]. Apalutamide, associated with increased risks of hypertension, bradycardia, and complete AV block, also requires careful patient monitoring. A meta-analysis found that both abiraterone and apalutamide were significantly associated with angina pectoris and myocardial infarction but not with the events identified in our study [19]. Apalutamide has been significantly linked to hypertension in another recent systematic review [20].
Flutamide significantly increases the risk of heart failure, suggesting that its use should be limited to patients with a history of heart failure or high risk. This is corroborated by a 2021 study that found that first-generation antiandrogens such as flutamide significantly increased the risks of heart failure and arrhythmias [21].
Abiraterone reduces the risk of coronary artery disease, angina pectoris, and unstable angina but increases the risk of heart failure, hypertension, atrial fibrillation, and cardiac arrest. This complex risk profile suggests that the benefits of abiraterone in reducing ischemic events need to be balanced against its potential to exacerbate heart failure and arrhythmias. A strong link between abiraterone and heart failure, arrhythmia, and coronary artery disease was uncovered in a recent study, as well as a weaker link to hypertension [22].
Olaparib shows a promising cardiovascular profile with a notably reduced risk of myocardial infarction. This finding indicates its potential safety in terms of the risk of ischemic heart disease. However, niraparib demonstrates an increased risk of hypertension and atrial flutter, which necessitates close monitoring of blood pressure and heart rhythm disturbances during treatment. When combined with antiandrogens, the risk of cardiac AEs increases; however, these agents are also associated with decreased cardiac AEs when administered in combination with chemotherapy/bevacizumab [23]. While having some cardioprotective effect, other studies have shown these drugs to be linked to major adverse cardiac events, with an incidence of 17.5% for hypertension [24].
This study does have several limitations. The FAERS database may be subject to incomplete or selective reporting, which could compromise data comprehensiveness and accuracy. Reporting biases might lead to over- or underestimation of the frequency and severity of adverse events. Additionally, confounding variables—such as patient demographics, concurrent medications, and pre-existing conditions—are often insufficiently captured, complicating the interpretation of findings. Finally, while such studies are valuable for identifying associations, they do not establish causality.
These findings highlight the importance of individualized patient assessment and the careful consideration of cardiovascular risk factors when selecting hormonal therapy and PARP inhibitors. The differential cardiovascular risks associated with each medication underscore the need for a tailored approach to treatment, especially in patients with existing cardiovascular conditions or those at higher risk for such events, which is a key demographic of patients with prostate cancer. A recent study found that 69.4% of their patients had at least one cardiovascular disease risk factor, and 53.4% had hypertension [3]. Moreover, while many studies have compared the rates of cardiovascular adverse events between different treatment regimens, future studies should focus on the unique adverse event profile associated with each drug or class as, from real-world data, the outcomes may vary widely (Table 1, Table 2 and Table 3). Moreover, studies should also investigate patient factors such as medication compliance, as well as the risks associated with combination therapies as many patients take multiple agents concurrently. Further research is essential to elucidate the mechanisms underlying these associations and develop strategies to mitigate cardiovascular risks while maintaining therapeutic efficacy in androgen suppression and prostate cancer treatment. This approach ensures optimal patient outcomes and enhances the safety of these therapeutic agents in patients with prostate cancer.
4. Materials and Methods
To conduct disproportionality analyses, the reported incidence of specific AEs for certain drugs was compared with the overall reported rate of AEs for all other pharmaceuticals. Using OpenVigil 2.1 (OpenVigil, Kiel, Germany) to access the FAERS database, individual queries were performed to retrieve the AEs for the LHRH agonists and antagonists leuprolide, goserelin, triptorelin, degarelix, and relugolix; the antiandrogens and androgen synthesis inhibitors bicalutamide, flutamide, apalutamide, nilutamide, abiraterone, and enzalutamide; and the PARP inhibitors olaparib, rucaparib, talazoparib, and niraparib. The FAERS is a publicly accessible database maintained by the U.S. Food and Drug Administration (FDA). It collects and analyzes AE reports, medication error reports, and product quality complaints related to drugs and therapeutic biologics. The FAERS plays a key role in post-market safety surveillance, supporting the FDA’s efforts to monitor drug safety. For this study, reports submitted from the fourth quarter of 2003 to the third quarter of 2023 were used for analysis. This cross-sectional study was filtered to only include men and not filtered for any additional clinical criteria. These data allowed the calculation of reporting odds ratios (RORs), gathering the likelihood of an AE in the presence of drug exposure compared to the odds of AEs in the absence of exposure, compared to all other drugs. The statistical significance for each ROR value was determined if the lower bound value of the 95% confidence interval exceeded 1.00, and the ROR was greater than 2.00. Only AEs with more than three reports were included. The results were filtered to include only reports of male patients. OpenVigil 2.1 incorporates data-cleaning procedures, including the removal of duplicate records, rectification of improperly formatted entries, and consolidation of terms referring to the same drug under a single term. MedDRA terms included in the study included the following: ischemic heart disease (myocardial infarction [MI], coronary artery disease [CAD], angina pectoris, unstable angina), heart failure, hypertension, arrhythmias (atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular tachycardia, supraventricular tachycardia, and bradycardia), cardiomyopathies (hypertrophic cardiomyopathy, ischemic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy), valvular heart disease (mitral valve disease, aortic valve disease, tricuspid valve disease, pulmonary valve disease), pericardial disease (pericarditis, pericardial effusion, cardiac tamponade), conduction disease (first-degree atrioventricular [AV] block, second-degree AV block, complete AV block), and other cardiac complications (cardiac arrest, myocarditis, endocarditis, cardiomegaly). Among the 4,049,329 unique adverse event reports, 4391 cardiovascular events were identified.
Funding
This research received no external funding.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Data sharing is not provided for this article as all the data utilized were publicly accessed from OpenVigil 2.1 (https://openvigil.sourceforge.net; accessed on 29 July 2024), and are thus already free to access.
Conflicts of Interest
The authors declare no conflicts of interest.
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Table 1.
LHRH agonists and antagonists.
| Adverse Events | Leuprolide | Goserelin | Triptorelin | Degarelix | Relugolix | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | |
| Ischemic Heart Disease | ||||||||||
| Myocardial Infarction | 237 | 0.481 (0.423, 0.547) | 16 | 2.235 (1.367, 3.654) | 13 | 0.527 (0.305, 0.909) | 6 | 1.288 (0.578, 2.870) | 18 | 0.587 (0.369, 0.934) |
| Coronary Artery Disease | 51 | 0.572 (0.435, 0.754) | 16 | 1.876 (1.148, 3.067) | 3 | 0.671 (0.216, 2.084) | n/a | n/a | n/a | n/a |
| Angina Pectoris | n/a | n/a | 8 | 1.354 (0.676, 2.710) | 4 | 1.296 (0.486, 3.459) | 3 | 0.781 (0.252, 2.424) | 3 | 0.781 (0.252, 2.424) |
| Unstable Angina | 6 | 0.345 (0.155, 0.768) | 4 | 2.402 (0.900, 6.410) | n/a | n/a | n/a | n/a | n/a | n/a |
| Heart Failure | 165 | 1.069 (0.917, 1.247) | 36 | 2.435 (1.752, 3.382) | 13 | 1.633 (0.946, 2.819) | 30 | 3.136 (2.186, 4.497) | 30 | 3.136 (2.186, 4.497) |
| Hypertension | n/a | n/a | n/a | n/a | 23 | 1.478 (0.979, 2.230) | 26 | 1.342 (0.911, 1.975) | n/a | n/a |
| Arrhythmia | n/a | n/a | ||||||||
| Atrial Fibrillation | 145 | 0.789 (0.67, 0.929) | 44 | 2.513 (1.866, 3.385) | 14 | 1.522 (0.900, 2.577) | 16 | 1.398 (0.855, 2.287) | 16 | 1.398 (0.855, 2.287) |
| Atrial Flutter | 12 | 0.682 (0.386, 1.202) | 9 | 5.347 (2.775, 10.300) | n/a | n/a | n/a | n/a | n/a | n/a |
| Ventricular Fibrillation | 13 | 0.552 (0.320, 0.953) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Ventricular Tachycardia | 18 | 0.510 (0.321, 0.811) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Supraventricular Tachycardia | n/a | n/a | 8 | 5.432 (2.710, 10.888) | n/a | n/a | n/a | n/a | n/a | n/a |
| Bradycardia | 10 | 0.540 (0.290, 1.005) | 10 | 0.965 (0.518, 1.795) | n/a | n/a | n/a | n/a | n/a | n/a |
| Cardiomyopathy | ||||||||||
| Hypertrophic Cardiomyopathy | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Ischemic Cardiomyopathy | 4 | 0.382 (0.143, 1.020) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Dilated Cardiomyopathy | 4 | 7.388 (2.689, 20.299) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Restrictive Cardiomyopathy | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Valvular Heart Disease | ||||||||||
| Mitral Valve Disease | n/a | n/a | n/a | n/a | n/a | n/a | 4 | 3.377 (1.265, 9.015) | 4 | 3.377 (1.265, 9.015) |
| Aortic Valve Disease | 7 | 2.001 (0.948, 4.225) | 3 | 4.152 (1.336, 12.906) | n/a | n/a | n/a | n/a | n/a | n/a |
| Tricuspid Valve Disease | n/a | n/a | n/a | n/a | n/a | n/a | 3 | 3.807 (1.225, 11.827) | 3 | 3.807 (1.225, 11.827) |
| Pulmonary Valve Disease | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Pericardial Disease | ||||||||||
| Pericarditis | 4 | 0.243 (0.091, 0.647) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Pericardial Effusion | 16 | 0.422 (0.258, 0.689) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Cardiac Tamponade | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Conduction Disease | ||||||||||
| First Degree AV Block | 5 | 0.588 (0.244, 1.415) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Second Degree AV Block | 3 | 0.513 (0.165, 1.596) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Complete AV Block | n/a | n/a | 4 | 3.067 (1.149, 8.186) | 3 | 4.408 (1.419, 13.696) | n/a | n/a | n/a | n/a |
| Other Cardiac Complications | ||||||||||
| Cardiac Arrest | 86 | 0.503 (0.407, 0.622) | 8 | 0.487 (0.243, 0.975) | n/a | n/a | 9 | 0.846 (0.440, 1.629) | 9 | 0.846 (0.440, 1.629) |
| Myocarditis | n/a | n/a | n/a | n/a | 3 | 2.720 (0.876, 8.447) | n/a | n/a | n/a | n/a |
| Endocarditis | 8 | 0.782 (0.390, 1.566) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Cardiomegaly | 17 | 0.699 (0.434, 1.126) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Total | 801 | 166 | 76 | 97 | 83 | |||||
Statistically significant results are bolded. AV, atrioventricular.
Table 2.
Antiandrogens and androgen synthesis inhibitors.
| Adverse Events | Enzalutamide | Bicalutamide | Apalutamide | Flutamide | Abiraterone | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | |
| Ischemic Heart Disease | ||||||||||
| Myocardial Infarction | 193 | 0.393 (0.341, 0.452) | 70 | 0.745 (0.588, 0.943) | 45 | 0.607 (0.452, 0.813) | 3 | 0.436 (0.140, 1.356) | 201 | 0.542 (0.472, 0.623) |
| Coronary Artery Disease | 35 | 0.394 (0.282, 0.549) | n/a | n/a | n/a | n/a | n/a | n/a | 14 | 0.208 (0.123, 0.351) |
| Angina Pectoris | 23 | 0.374 (0.248, 0.563) | 11 | 0.932 (0.516, 1.685) | n/a | n/a | n/a | n/a | 26 | 0.560 (0.381, 0.823) |
| Unstable Angina | 3 | 0.173 (0.056, 0.536) | 10 | 3.019 (1.621, 5.622) | n/a | n/a | n/a | n/a | 3 | 0.229 (0.074, 0.710) |
| Heart Failure | 200 | 1.305 (1.135, 1.501) | 109 | 3.730 (3.085, 4.510) | n/a | n/a | 9 | 4.215 (2.179, 8.152) | 167 | 1.440 (1.236, 1.678) |
| Hypertension | 391 | 1.878 (1.698, 2.076) | 91 | 1.532 (1.245, 1.885) | 110 | 2.371 (1.962, 2.864) | 3 | 1.010 (0.325, 3.143) | 425 | 1.837 (1.669, 2.023) |
| Arrhythmia | ||||||||||
| Atrial Fibrillation | 156 | 0.853 (0.729, 0.999) | 54 | 1.538 (1.176, 2.011) | 37 | 1.336 (0.967, 1.847) | n/a | n/a | 199 | 1.448 (1.258, 1.665) |
| Atrial Flutter | 9 | 0.513 (0.266, 0.987) | 10 | 2.975 (1.597, 5.540) | 3 | 1.128 (0.364, 3.503) | n/a | n/a | 12 | 0.906 (0.513, 1.598) |
| Ventricular Fibrillation | 6 | 0.255 (0.115, 0.569) | 14 | 3.122 (1.845, 5.281) | n/a | n/a | n/a | n/a | 12 | 0.677 (0.384, 1.194) |
| Ventricular Tachycardia | 10 | 0.284 (0.153, 0.528) | 5 | 0.740 (0.308, 1.780) | 4 | 0.752 (0.282, 2.005) | n/a | n/a | 17 | 0.640 (0.398, 1.031) |
| Supraventricular Tachycardia | n/a | n/a | 6 | 2.036 (0.913, 4.540) | 5 | 2.154 (0.895, 5.183) | n/a | n/a | 6 | 0.516 (0.232, 1.151) |
| Bradycardia | 36 | 0.334 (0.241, 0.463) | 26 | 1.259 (0.857, 1.852) | 5 | 0.306 (0.127, 0.736) | n/a | n/a | 18 | 0.220 (0.139, 0.350) |
| Cardiomyopathy | ||||||||||
| Hypertrophic Cardiomyopathy | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Ischemic Cardiomyopathy | 4 | 0.384 (0.144, 1.025) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Dilated Cardiomyopathy | n/a | n/a | 4 | 38.702 (14.083, 106.359) | n/a | n/a | n/a | n/a | n/a | n/a |
| Restrictive Cardiomyopathy | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Valvular Heart Disease | ||||||||||
| Mitral Valve Disease | 11 | 0.580 (0.321, 1.049) | 7 | 1.923 (0.915, 4.040) | n/a | n/a | n/a | n/a | 7 | 0.488 (0.232, 1.024) |
| Aortic Valve Disease | 4 | 0.532 (0.199, 1.421) | 4 | 2.776 (1.039, 7.417) | n/a | n/a | n/a | n/a | 5 | 0.881 (0.366, 2.123) |
| Tricuspid Valve Disease | n/a | n/a | 3 | 1.237 (0.398, 3.840) | n/a | n/a | n/a | n/a | 3 | 0.314 (0.101, 0.974) |
| Pulmonary Valve Disease | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Pericardial Disease | ||||||||||
| Pericarditis | 3 | 0.183 (0.059, 0.567) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Pericardial Effusion | 26 | 0.690 (0.469, 1.015) | 5 | 0.688 (0.286, 1.655) | n/a | n/a | n/a | n/a | 18 | 0.631 (0.397, 1.002) |
| Cardiac Tamponade | 5 | 0.470 (0.195, 1.130) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Conduction Disease | ||||||||||
| First Degree AV Block | n/a | n/a | 6 | 3.698 (1.657, 8.255) | n/a | n/a | n/a | n/a | n/a | n/a |
| Second Degree AV Block | 3 | 0.515 (0.166, 1.602) | n/a | n/a | n/a | n/a | n/a | n/a | 3 | 0.682 (0.219, 2.120) |
| Complete AV Block | 9 | 0.665 (0.345, 1.280) | 7 | 2.694 (1.282, 5.662) | n/a | n/a | n/a | n/a | n/a | n/a |
| Other Cardiac Complications | ||||||||||
| Cardiac Arrest | 52 | 0.305 (0.232, 0.400) | 26 | 0.795 (0.541, 1.169) | 32 | 1.370 (0.968, 1.941) | 3 | 1.262 (0.405, 3.926) | 50 | 0.388 (0.294, 0.512) |
| Myocarditis | 6 | 0.273 (0.122, 0.608) | n/a | n/a | n/a | n/a | n/a | n/a | 3 | 0.180 (0.058, 0.559) |
| Endocarditis | 3 | 0.293 (0.094, 0.91) | 3 | 1.528 (0.492, 4.747) | n/a | n/a | n/a | n/a | 3 | 0.388 (0.125, 1.204) |
| Cardiomegaly | 13 | 0.536 (0.311, 0.924) | 11 | 2.365 (1.308, 4.278) | n/a | n/a | n/a | n/a | 4 | 0.217 (0.082, 0.580) |
| Total | 1201 | 482 | 241 | 18 | 1196 | |||||
Statistically significant results are bolded. AV, atrioventricular.
Table 3.
PARP inhibitors.
| Adverse Events | Olaparib | Rucaparib | Talazoparib | Niraparib | ||||
|---|---|---|---|---|---|---|---|---|
| Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | Events (n) | ROR (95% CI) | |
| Ischemic Heart Disease | ||||||||
| Myocardial Infarction | 4 | 0.145 (0.054, 0.386) | n/a | n/a | 4 | 1.503 (0.558, 4.047) | n/a | n/a |
| Coronary Artery Disease | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Angina Pectoris | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Unstable Angina | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Heart Failure | 5 | 0.576 (0.239, 1.385) | n/a | n/a | n/a | n/a | n/a | n/a |
| Hypertension | n/a | n/a | 3 | 1.108 (0.355, 3.456) | n/a | n/a | 5 | 4.154 (1.709, 10.092) |
| Arrhythmia | ||||||||
| Atrial Fibrillation | 3 | 0.291 (0.094, 0.902) | n/a | n/a | n/a | n/a | 3 | 2.853 (0.912, 8.923) |
| Atrial Flutter | n/a | n/a | n/a | n/a | 3 | 31.564 (10.080, 98.837) | n/a | n/a |
| Ventricular Fibrillation | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Ventricular Tachycardia | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Supraventricular Tachycardia | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Bradycardia | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |
| Total | 12 | 3 | 7 | 8 | ||||
Statistically significant results are bolded.
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Frey, C. Cardiovascular Adverse Events Associated with Prostate Cancer Treatment: A Disproportionality Analysis from the Food and Drug Administration Adverse Event Reporting System Database. Pharmacoepidemiology 2024, 3, 373-382. https://doi.org/10.3390/pharma3040026
AMA Style
Frey C. Cardiovascular Adverse Events Associated with Prostate Cancer Treatment: A Disproportionality Analysis from the Food and Drug Administration Adverse Event Reporting System Database. Pharmacoepidemiology. 2024; 3(4):373-382. https://doi.org/10.3390/pharma3040026
Chicago/Turabian StyleFrey, Connor. 2024. "Cardiovascular Adverse Events Associated with Prostate Cancer Treatment: A Disproportionality Analysis from the Food and Drug Administration Adverse Event Reporting System Database" Pharmacoepidemiology 3, no. 4: 373-382. https://doi.org/10.3390/pharma3040026
APA StyleFrey, C. (2024). Cardiovascular Adverse Events Associated with Prostate Cancer Treatment: A Disproportionality Analysis from the Food and Drug Administration Adverse Event Reporting System Database. Pharmacoepidemiology, 3(4), 373-382. https://doi.org/10.3390/pharma3040026
