ADT and Increased Cardiovascular Mortality

Among men with unfavorable-risk, nonmetastatic prostate cancer, the use of androgen deprivation therapy (ADT) was not associated with an increase in cardiovascular mortality as some previous studies had suggested, according to results of a recent meta-analysis [JAMA. 2011;306(21):2359-2366]. Researchers recently conducted the meta-analysis of randomized, controlled, multicenter phase 3 trials to establish whether there is a link between ADT use and cardiovascular mortality, prostate cancer–specific mortality (PCSM), and all-cause mortality. The trials consisted of men with unfavorable-risk, nonmetastatic and nonhormone-refractory prostate cancer and took place between 1966 and April 2011. The intervention group received immediate ADT (predominantly gonadotropin-releasing hormone agonist) and the control group did not. For study eligibility, the median follow-up had to be at least 1 year. Of 1041 identified trials, the meta-analysis ultimately included 8 trials that yielded information on cardiovascular mortality; a total of 11 trials also provided data on PCSM and all-cause mortality. The median follow-up of these trials varied from 7.6 to 13.2 years. The length of time patients were treated with ADT ranged from 3 months to lifelong. Among the 8 trials, there were 2200 patients treated with ADT and 1941 patients in the control group. Results showed a total of 255 cardiovascular deaths in the intervention group (overall incidence, 11.0%; P<.001) compared with 252 in the control group (overall incidence, 11.2%; P<.001). The corresponding relative risk (RR) for cardiovascular death for the ADT group versus the control group was not found to be significant (0.93; 95% confidence interval, 0.79-1.10; P=.41). In short-course ADT trials (≤6 months of use) the researchers found an incidence of fatal cardiovascular events for the ADT group to be 10.5% compared with 10.3% for the control group (RR, 1.00; P=.99). In long-course ADT trials (use of ADT from 3 years to lifelong), the researchers found an incidence of fatal cardiovascular events for the ADT group to be 11.5% for both the intervention and control groups (RR, 0.91; P=.34). No statistically significant differences were found in RRs between short- and long-course trials. The researchers also found no association between ADT use and cardiovascular death when stratifying the trials by age (median age of ≥70 years or <70 years). Patients who underwent radiation therapy in addition to ADT also had no evidence of excess cardiovascular death resulting from ADT. In the analysis of PCSM and all-cause mortality, results showed 443 PCSM deaths among 2527 patients taking ADT (incidence rate, 13.5%) and 552 PCSM deaths in the control group of 2278 patients (incidence rate, 22.1%). Researchers found an RR of 0.69 in favor of ADT use. There were also 1140 total deaths in the ADT group compared with 1213 total deaths in the control group, which translated to an incidence of all-cause mortality of 37.7% for patients receiving ADT compared with 44.4% for patients in the control group. The RR of death was 0.86 (P<.001). A possible limitation of the study was a lack of stratification according to preexisting cardiovascular comorbidities. It is not known if patients having underlying cardiac disease could experience excess cardiovascular mortality due to ADT. In conclusion, the researchers recommended that future randomized trials of patients with cardiovascular comorbidities be performed.