Cardiovascular Disease Unit IRCCS Ospedale Policlinico San MartinoIRCCS Italian Cardiovascular Network Genova Italy.
Department of Internal Medicine University of Genova Italy.
J Am Heart Assoc. 2020 Sep 15;9(18):e016309. doi: 10.1161/JAHA.119.016309. Epub 2020 Aug 31.
Background The burden of cancer in heart failure with reduced ejection fraction is apparently growing. Randomized controlled trials (RCTs) may help understanding this observation, since they span decades of heart failure treatment. Methods and Results We assessed cancer, cardiovascular, and total mortality in phase 3 heart failure RCTs involving ≥90% individuals with left ventricular ejection fraction <45%, who were not acutely decompensated and did not represent specific patient subsets. The pooled odds ratios (ORs) of each type of death for the control and treatment arms were calculated using a random-effects model. Temporal trends and the impact of patient and RCT characteristics on mortality outcomes were evaluated by meta-regression analysis. Cancer mortality was reported for 15 (25%) of 61 RCTs, including 33 709 subjects, and accounted for 6% to 14% of all deaths and 17% to 67% of noncardiovascular deaths. Cancer mortality rate was 0.58 (95% CI, 0.46-0.71) per 100 patient-years without temporal trend (=0.35). Cardiovascular (=0.001) and total (=0.001) mortality rates instead decreased over time. Moreover, cancer mortality was not influenced by treatment (OR, 1.08; 95% CI, 0.92-1.28), unlike cardiovascular (OR, 0.88; 95% CI, 0.79-0.98) and all-cause (OR, 0.91; 95% CI, 0.84-0.99) mortality. Meta-regression did not reveal significant sources of heterogeneity. Possible reasons for excluding patients with malignancy overlapped among RCTs with and without published cancer mortality, and malignancy was an exclusion criterion only for 4 (8.7%) of the RCTs not reporting cancer mortality. Conclusions Cancer is a major, yet overlooked cause of noncardiovascular death in heart failure with reduced ejection fraction, which has become more prominent with cardiovascular mortality decline.
射血分数降低的心力衰竭中的癌症负担显然在增加。随机对照试验（RCT）可能有助于理解这一观察结果，因为它们涵盖了心力衰竭治疗的几十年。
我们评估了涉及左心室射血分数<45%且无急性失代偿且不代表特定患者亚组的 3 期心力衰竭 RCT 中癌症、心血管和总死亡率。使用随机效应模型计算每种死亡类型的控制组和治疗组的合并优势比（OR）。通过荟萃回归分析评估时间趋势以及患者和 RCT 特征对死亡率结果的影响。15（25%）项 RCT 报告了癌症死亡率，共包括 33709 例患者，占所有死亡的 6%至 14%和非心血管死亡的 17%至 67%。无时间趋势时，癌症死亡率为每 100 例患者年 0.58（95%CI，0.46-0.71）（=0.35）。相反，心血管（=0.001）和总（=0.001）死亡率随着时间的推移而降低。此外，与心血管（OR，0.88；95%CI，0.79-0.98）和全因（OR，0.91；95%CI，0.84-0.99）死亡率不同，癌症死亡率不受治疗影响（OR，1.08；95%CI，0.92-1.28）。荟萃回归未发现显著的异质性来源。在有和没有发表癌症死亡率的 RCT 中，排除恶性肿瘤患者的可能原因重叠，并且仅将恶性肿瘤作为 4 项（8.7%）未报告癌症死亡率的 RCT 的排除标准。
癌症是射血分数降低的心力衰竭中非心血管死亡的主要但被忽视的原因，随着心血管死亡率的下降，其重要性变得更加突出。
