背景:临床前动物研究表明,骨髓细胞合成的凝血因子X抑制抗肿瘤免疫,利伐沙班,直接因子Xa抑制剂,可用于促进肿瘤免疫。这项研究旨在评估服用直接因子Xa抑制剂的房颤患者是否比服用直接凝血酶抑制剂达比加群的患者具有更低的癌症风险和癌症相关死亡率。
结果:这项在丹麦进行的以人群为基础的全国性队列研究包括患有房颤且没有癌症史的成年患者,他们在2011年至2015年间开始服用因子Xa抑制剂或达比加群。病史资料,结果,和药物使用是通过丹麦医疗保健登记处获得的。主要结果是任何癌症。次要结局是癌症相关死亡率和全因死亡率。在5年的随访中,在意向治疗分析中评估结果事件。基于倾向评分的治疗加权的逆概率用于计算累积发生率和子分布风险比(SHR)和相应的95%置信区间(CI)。将死亡视为一项竞争事件。倾向得分使用逻辑回归进行估计,并包括在模型性别中,索引日期的年龄组,合并症,和使用粉刺。总共包括11,742名开始使用Xa因子抑制剂的房颤患者和11,970名开始使用达比加群的患者。因子Xa队列的平均年龄为75.2岁(标准差[SD]11.2),达比加群队列的平均年龄为71.7岁(SD11.1)。在倾向得分加权模型的基础上,经过5年的随访,在Xa因子抑制剂之间观察到癌症的累积发病率没有实质性差异(2,157/23,711;9.11%,95%CI[8.61%,9.63%])和达比加群(2,294/23,715;9.68%,95%CI[9.14%,10.25%])组(SHR0.94,95%CI[0.89,1.00],P值0.0357)。我们观察到癌症相关死亡率没有差异(因子Xa抑制剂队列1,028/23,711;4.33%,95%CI[4.02%,4.68%]。达比加群1,001/23,715;4.22%,95%CI[3.83%,4.66%];SHR1.03,95%CI[0.94,1.12]),但是全因死亡率在因子Xa抑制剂队列中更高(因子Xa抑制剂队列7,416/23,711;31.31%,95%CI[30.37%,32.29%]。达比加群6,531/23,715;27.56%,95%CI[26.69%,28.45%];HR1.17,95%CI[1.13,1.21])。该研究的主要局限性是残留混杂的可能性和较短的随访期。
结论:在这项基于人群的队列研究中,与达比加群相比,使用因子Xa抑制剂与总体较低的癌症发病率或癌症相关死亡率无关.我们确实观察到在因子Xa抑制剂队列中全因死亡率增加。
BACKGROUND: Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This
study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran.
RESULTS: This nationwide population-based cohort
study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the
study were the possibility of residual confounding and the short follow-up period.
CONCLUSIONS: In this population based cohort
study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.