Sorbonne Université, Improving Emergency Care FHU, Paris, France.
Emergency Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
JAMA. 2021 Dec 7;326(21):2141-2149. doi: 10.1001/jama.2021.20750.
Uncontrolled studies suggest that pulmonary embolism (PE) can be safely ruled out using the YEARS rule, a diagnostic strategy that uses varying D-dimer thresholds.
To prospectively validate the safety of a strategy that combines the YEARS rule with the pulmonary embolism rule-out criteria (PERC) rule and an age-adjusted D-dimer threshold.
DESIGN, SETTINGS, AND PARTICIPANTS: A cluster-randomized, crossover, noninferiority trial in 18 emergency departments (EDs) in France and Spain. Patients (N = 1414) who had a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE were included from October 2019 to June 2020, and followed up until October 2020.
Each center was randomized for the sequence of intervention periods. In the intervention period (726 patients), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1000 ng/mL and in patients with 1 or more YEARS criteria and a D-dimer level less than the age-adjusted threshold (500 ng/mL if age <50 years or age in years × 10 in patients ≥50 years). In the control period (688 patients), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold.
The primary end point was venous thromboembolism (VTE) at 3 months. The noninferiority margin was set at 1.35%. There were 8 secondary end points, including chest imaging, ED length of stay, hospital admission, nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months.
Of the 1414 included patients (mean age, 55 years; 58% female), 1217 (86%) were analyzed in the per-protocol analysis. PE was diagnosed in the ED in 100 patients (7.1%). At 3 months, VTE was diagnosed in 1 patient in the intervention group (0.15% [95% CI, 0.0% to 0.86%]) vs 5 patients in the control group (0.80% [95% CI, 0.26% to 1.86%]) (adjusted difference, -0.64% [1-sided 97.5% CI, -∞ to 0.21%], within the noninferiority margin). Of the 6 analyzed secondary end points, only 2 showed a statistically significant difference in the intervention group compared with the control group: chest imaging (30.4% vs 40.0%; adjusted difference, -8.7% [95% CI, -13.8% to -3.5%]) and ED median length of stay (6 hours [IQR, 4 to 8 hours] vs 6 hours [IQR, 5 to 9 hours]; adjusted difference, -1.6 hours [95% CI, -2.3 to -0.9]).
Among ED patients with suspected PE, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients, compared with a conventional diagnostic strategy, did not result in an inferior rate of thromboembolic events.
ClinicalTrials.gov Identifier: NCT04032769.
一些非控制性研究表明，使用 YEARS 规则（一种使用不同 D-二聚体阈值的诊断策略）可以安全地排除肺栓塞 (PE)。
前瞻性验证一种结合 YEARS 规则和肺栓塞排除标准 (PERC)规则以及年龄调整 D-二聚体阈值的策略的安全性。
设计、地点和参与者：一项在法国和西班牙的 18 个急诊部门进行的集群随机交叉非劣效性试验。纳入 2019 年 10 月至 2020 年 6 月间，具有低临床 PE 风险但 PERC 规则未排除或主观临床中等 PE 风险的患者（N=1414），并随访至 2020 年 10 月。
每个中心按干预顺序随机分组。在干预期（726 例患者）中，如果无 YEARS 标准且 D-二聚体水平<1000ng/mL，或有 1 个或多个 YEARS 标准且 D-二聚体水平<年龄调整阈值（<50 岁为 500ng/mL，≥50 岁为年龄×10ng/mL），则无需进行胸部影像学检查即可排除 PE。在对照组（688 例患者）中，如果 D-二聚体水平低于年龄调整阈值，则无需进行胸部影像学检查即可排除 PE。
主要终点为 3 个月时的静脉血栓栓塞症 (VTE)。非劣效性边界设定为 1.35%。有 8 个次要终点，包括胸部影像学、急诊留观时间、住院、不必要抗凝治疗、全因死亡和 3 个月时的全因再入院。
在纳入的 1414 例患者（平均年龄 55 岁，58%为女性）中，1217 例（86%）进行了意向性分析。在 ED 诊断出 100 例 PE（7.1%）。在 3 个月时，干预组有 1 例（0.15% [95%CI，0.0%至 0.86%]）诊断为 VTE，而对照组有 5 例（0.80% [95%CI，0.26%至 1.86%]）（调整差异，-0.64% [1 侧 97.5%CI，-∞至 0.21%]，在非劣效性边界内）。在分析的 6 个次要结局中，仅 2 个在干预组与对照组之间存在统计学显著差异：胸部影像学（30.4%比 40.0%；调整差异，-8.7% [95%CI，-13.8%至-3.5%]）和 ED 中位留观时间（6 小时 [IQR，4 至 8 小时]比 6 小时 [IQR，5 至 9 小时]；调整差异，-1.6 小时 [95%CI，-2.3 至-0.9]）。
在疑似 PE 的 ED 患者中，与传统诊断策略相比，在 PERC 阳性患者中使用 YEARS 规则结合年龄调整 D-二聚体阈值并不会导致血栓栓塞事件发生率降低。
ClinicalTrials.gov 标识符：NCT04032769。
