title: The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer.
abstract: OBJECTIVE
  New hormonal agents are available for treating metastatic castration-resistant prostate cancer (mCRPC). We aim to define the incidence and relative risk (RR) of cardiovascular events in mCRPC patients treated with these agents.
  
  
  METHODS
  Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods.
  
  
  RESULTS
  We included six articles in this meta-analysis covering a total of 6735 patients who were used to evaluate cardiac toxicity. The use of new hormonal agents was associated with an increased risk of all grades of such toxicity (RR=1.32, 95% CI, 1.08-1.60; p=0.006) compared to a placebo, even if the absolute difference in terms of incidence was small at 14.8% versus 11.5%, respectively. No increased risk of grade 3-4 events (RR=1.35, 95% CI, 0.90-2.03; p=0.15) was observed. A total of 7830 patients were used to evaluate hypertension, and it was found that the use of new hormonal agents compared to a placebo was associated with an increased risk of all-grades (RR=1.84, 95% CI, 1.37-2.46; p<0.001) and grade 3-4 events (RR=1.77, 95% CI, 1.13-2.77; p=0.01). The absolute incidence was 12.5% versus 7.5% for all-grades and 3.7% versus 2.4% for grade 3-4.
  
  
  CONCLUSIONS
  This analysis revealed a significant increase in the incidence and RR of cardiovascular toxicity in mCRPC treated with new hormonal agents as opposed to a placebo, even though the occurrence of all- and grade 3-4 events rose only 14% and 4%, respectively. Follow-ups for the onset of treatment-related cardiovascular events should therefore be considered in these patients.
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; Department of Radiology, Oncology and Human Pathology, "Sapienza" University of Rome, Viale Regina Elena 324, 00161 Rome, Italy. Electronic address: roberto.iacovelli@ieo.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Verri
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cossu Rocca
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Aurilio
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cullurà
authors.affiliation: Division of Urology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Ottavio
authors.initials: O
authors.lastname: De Cobelli
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Nolè
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D016009:Chi-Square Distribution; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D015994:Incidence; D008297:Male; D016017:Odds Ratio; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal
keywords: Abiraterone acetate; Arterial hypertension; CRPC; Cardiac toxicity; Enzalutamide; Orteronel; Prostate cancer; Safety