Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Royal College of General Practitioners, London, United Kingdom.
PLoS One. 2022 Sep 1;17(9):e0265998. doi: 10.1371/journal.pone.0265998. eCollection 2022.
We investigated differences in risk of stroke, with all-cause mortality as a competing risk, in people newly diagnosed with atrial fibrillation (AF) who were commenced on either direct oral anticoagulants (DOACs) or warfarin treatment.
We conducted a retrospective cohort study of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database (a network of 500 English general practices). We compared long term exposure to DOAC (n = 5,168) and warfarin (n = 7,451) in new cases of AF not previously treated with oral anticoagulants. Analyses included: survival analysis, estimating cause specific hazard ratios (CSHR), Fine-Gray analysis for factors affecting cumulative incidence of events occurring over time and a cumulative risk regression with time varying effects.We found no difference in CSHR between stroke 1.08 (0.72-1.63, p = 0.69) and all-cause mortality 0.93 (0.81-1.08, p = 0.37), or between the anticoagulant groups. Fine-Gray analysis produced similar results 1.07 (0.71-1.6 p = 0.75) for stroke and 0.93 (0.8-1.07, p = 0.3) mortality. The cumulative risk of mortality with DOAC was significantly elevated in early follow-up (67 days), with cumulative risk decreasing until 1,537 days and all-cause mortality risk significantly decreased coefficient estimate:: -0.23 (-0.38-0.01, p = 0.001); which persisted over seven years of follow-up.
In this large, contemporary, real world primary care study with longer follow-up, we found no overall difference in the hazard of stroke between warfarin and DOAC treatment for AF. However, there was a significant time-varying effect between anti-coagulant regimen on all-cause mortality, with DOACs showing better survival. This is a key methodological observation for future follow-up studies, and reassuring for patients and health care professionals for longer duration of therapy.
我们研究了新发心房颤动（AF）患者在开始使用直接口服抗凝剂（DOAC）或华法林治疗后，因中风导致的风险差异，以全因死亡率为竞争风险。
我们对牛津皇家全科医师学院（RCGP）研究和监测中心（RSC）数据库（一个由 500 家英国全科诊所组成的网络）进行了回顾性队列研究。我们比较了新诊断为 AF 且未接受过口服抗凝剂治疗的患者中 DOAC（n=5168）和华法林（n=7451）的长期暴露情况。分析包括：生存分析，估计特定原因风险比（CSHR），Fine-Gray 分析影响随时间发生的累积事件发生率的因素，以及具有时间变化效应的累积风险回归。
我们发现中风的 CSHR 无差异 1.08（0.72-1.63，p=0.69）和全因死亡率 0.93（0.81-1.08，p=0.37），或抗凝剂组之间也无差异。Fine-Gray 分析得出相似的结果 1.07（0.71-1.6，p=0.75）为中风和 0.93（0.8-1.07，p=0.3）死亡率。在早期随访（67 天）中，DOAC 的死亡率累积风险明显升高，累积风险在 1537 天后降低，全因死亡率风险显著降低系数估计值：-0.23（-0.38-0.01，p=0.001）；这种情况持续了七年的随访。
在这项具有更长随访时间的大型、当代真实世界的初级保健研究中，我们发现华法林和 DOAC 治疗 AF 中风的风险无总体差异。然而，两种抗凝方案之间存在全因死亡率的显著时间变化效应，DOAC 显示出更好的生存。这是未来随访研究的一个关键方法学观察结果，对患者和医疗保健专业人员来说，在更长的治疗时间内是令人安心的。
