Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
JAMA. 2011 Dec 7;306(21):2359-66. doi: 10.1001/jama.2011.1745.
Whether androgen deprivation therapy (ADT) causes excess cardiovascular deaths in men with prostate cancer is highly controversial and was the subject of a joint statement by multiple medical societies and a US Food and Drug Administration safety warning.
To perform a systematic review and meta-analysis of randomized trials to determine whether ADT is associated with cardiovascular mortality, prostate cancer-specific mortality (PCSM), and all-cause mortality in men with unfavorable-risk, nonmetastatic prostate cancer.
A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases for relevant randomized controlled trials in English between January 1, 1966, and April 11, 2011.
Inclusion required nonmetastatic disease, intervention group with gonadotropin-releasing hormone agonist-based ADT, control group with no immediate ADT, complete information on cardiovascular deaths, and median follow-up of more than 1 year.
Extraction was by 2 independent reviewers. Summary incidence, relative risk (RR), and CIs were calculated using random-effects or fixed-effects models.
Among 4141 patients from 8 randomized trials, cardiovascular death in patients receiving ADT vs control was not significantly different (255/2200 vs 252/1941 events; incidence, 11.0%; 95% CI, 8.3%-14.5%; vs 11.2%; 95% CI, 8.3%-15.0%; RR, 0.93; 95% CI, 0.79-1.10; P = .41). ADT was not associated with excess cardiovascular death in trials of at least 3 years (long duration) of ADT (11.5%; 95% CI, 8.1%-16.0%; vs 11.5%; 95% CI, 7.5%-17.3%; RR, 0.91; 95% CI, 0.75-1.10; P = .34) or in trials of 6 months or less (short duration) of ADT (10.5%; 95% CI, 6.3%-17.0%; vs 10.3%; 95% CI, 8.2%-13.0%; RR, 1.00; 95% CI, 0.73-1.37; P = .99). Among 4805 patients from 11 trials with overall death data, ADT was associated with lower PCSM (443/2527 vs 552/2278 events; 13.5%; 95% CI, 8.8%-20.3%; vs 22.1%; 95% CI, 15.1%-31.1%; RR, 0.69; 95% CI, 0.56-0.84; P < .001) and lower all-cause mortality (1140/2527 vs 1213/2278 events; 37.7%; 95% CI, 27.3%-49.4%; vs 44.4%; 95% CI, 32.5%-57.0%; RR, 0.86; 95% CI, 0.80-0.93; P < .001).
In a pooled analysis of randomized trials in unfavorable-risk prostate cancer, ADT use was not associated with an increased risk of cardiovascular death but was associated with a lower risk of PCSM and all-cause mortality.
雄激素剥夺疗法（ADT）是否会导致前列腺癌男性的心血管死亡增加，这是一个极具争议的问题，也是多个医学协会和美国食品和药物管理局（FDA）安全警告的主题。
进行系统评价和荟萃分析，以确定 ADT 是否与不利风险、非转移性前列腺癌男性的心血管死亡率、前列腺癌特异性死亡率（PCSM）和全因死亡率相关。
对 1966 年 1 月 1 日至 2011 年 4 月 11 日期间发表的英文随机对照试验进行了 MEDLINE、EMBASE 和 Cochrane 中央对照试验注册数据库的检索。
纳入标准为非转移性疾病、使用促性腺激素释放激素激动剂的 ADT 干预组、无立即 ADT 的对照组、完整的心血管死亡信息以及中位随访时间超过 1 年。
由 2 名独立评审员进行提取。使用随机效应或固定效应模型计算汇总发生率、相对风险（RR）和置信区间。
在 8 项随机试验的 4141 名患者中，接受 ADT 的患者与对照组的心血管死亡无显著差异（255/2200 与 252/1941 例事件；发生率，11.0%；95%CI，8.3%-14.5%；vs 11.2%；95%CI，8.3%-15.0%；RR，0.93；95%CI，0.79-1.10；P =.41）。在至少 3 年（长疗程）ADT 的试验（11.5%；95%CI，8.1%-16.0%；vs 11.5%；95%CI，7.5%-17.3%；RR，0.91；95%CI，0.75-1.10；P =.34）或 6 个月或更短（短疗程）ADT 的试验（10.5%；95%CI，6.3%-17.0%；vs 10.3%；95%CI，8.2%-13.0%；RR，1.00；95%CI，0.73-1.37；P =.99）中，ADT 并未导致心血管死亡增加。在 11 项具有总体死亡数据的试验中，共有 4805 名患者，ADT 与较低的 PCSM 相关（443/2527 与 552/2278 例事件；13.5%；95%CI，8.8%-20.3%；vs 22.1%；95%CI，15.1%-31.1%；RR，0.69；95%CI，0.56-0.84；P <.001）和较低的全因死亡率（1140/2527 与 1213/2278 例事件；37.7%；95%CI，27.3%-49.4%；vs 44.4%；95%CI，32.5%-57.0%；RR，0.86；95%CI，0.80-0.93；P <.001）。
在不利风险前列腺癌的随机试验汇总分析中，ADT 使用与心血管死亡风险增加无关，但与 PCSM 和全因死亡率降低相关。
