Susu Zhou , Parissa Alerasool , Noriko Kishi , Himanshu Joshi , Gagan Sahni , Che-Kai Tsao
{"title":"前列腺癌患者使用雄激素受体轴靶向药物的心血管毒性:随机对照试验的元分析","authors":"Susu Zhou , Parissa Alerasool , Noriko Kishi , Himanshu Joshi , Gagan Sahni , Che-Kai Tsao","doi":"10.1016/j.clgc.2024.102066","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities.</p></div><div><h3>Patients and Methods</h3><p>We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted.</p></div><div><h3>Results</h3><p>A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, <em>P = .</em>04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, <em>P = .</em>007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, <em>P = .</em>05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, <em>P = .</em>02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, <em>P = .</em>01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, <em>P = .</em>04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, <em>P = .</em>03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, <em>P = .</em>01), respectively.</p></div><div><h3>Conclusion</h3><p>The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors.</p></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cardiovascular Toxicity Associated With Androgen Receptor Axis-Targeted Agents in Patients With Prostate Cancer: A Meta-analysis of Randomized Controlled Trials\",\"authors\":\"Susu Zhou , Parissa Alerasool , Noriko Kishi , Himanshu Joshi , Gagan Sahni , Che-Kai Tsao\",\"doi\":\"10.1016/j.clgc.2024.102066\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities.</p></div><div><h3>Patients and Methods</h3><p>We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted.</p></div><div><h3>Results</h3><p>A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, <em>P = .</em>04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, <em>P = .</em>007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, <em>P = .</em>05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, <em>P = .</em>02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, <em>P = .</em>01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, <em>P = .</em>04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, <em>P = .</em>03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, <em>P = .</em>01), respectively.</p></div><div><h3>Conclusion</h3><p>The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors.</p></div>\",\"PeriodicalId\":10380,\"journal\":{\"name\":\"Clinical genitourinary cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical genitourinary cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1558767324000399\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical genitourinary cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1558767324000399","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Cardiovascular Toxicity Associated With Androgen Receptor Axis-Targeted Agents in Patients With Prostate Cancer: A Meta-analysis of Randomized Controlled Trials
Introduction
Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities.
Patients and Methods
We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted.
Results
A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, P = .04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, P = .007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, P = .05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, P = .02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, P = .01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, P = .04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, P = .03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, P = .01), respectively.
Conclusion
The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors.
期刊介绍:
Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.