Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
Department of Neurological Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
PLoS One. 2023 Jan 30;18(1):e0274243. doi: 10.1371/journal.pone.0274243. eCollection 2023.
Coronavirus disease 2019 (COVID-19) is an immunoinflammatory and hypercoagulable state that contributes to respiratory distress, multi-organ dysfunction, and mortality. Dipyridamole, by increasing extracellular adenosine, has been postulated to be protective for COVID-19 patients through its immunosuppressive, anti-inflammatory, anti-coagulant, vasodilatory, and anti-viral actions. Likewise, low-dose aspirin has also demonstrated protective effects for COVID-19 patients. This study evaluated the effect of these two drugs formulated together as Aggrenox in hospitalized COVID-19 patients.
In an open-label, single site randomized controlled trial (RCT), hospitalized COVID-19 patients were assigned to adjunctive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) with standard of care treatment compared to standard of care treatment alone. Primary endpoint was illness severity according to changes on the eight-point COVID ordinal scale, with levels of 1 to 8 where higher scores represent worse illness. Secondary endpoints included all-cause mortality and respiratory failure. Outcomes were measured through days 14, 28, and/or hospital discharge.
From October 1, 2020 to April 30, 2021, a total of 98 patients, who had a median [IQR] age of 57 [47, 62] years and were 53.1% (n = 52) female, were randomized equally between study groups (n = 49 Aggrenox plus standard of care versus n = 49 standard of care alone). No clinically significant differences were found between those who received adjunctive Aggrenox and the control group in terms of illness severity (COVID ordinal scale) at days 14 and 28. The overall mortality through day 28 was 6.1% (3 patients, n = 49) in the Aggrenox group and 10.2% (5 patients, n = 49) in the control group (OR [95% CI]: 0.40 [0.04, 4.01], p = 0.44). Respiratory failure through day 28 occurred in 4 (8.3%, n = 48) patients in the Aggrenox group and 7 (14.6%, n = 48) patients in the standard of care group (OR [95% CI]: 0.21 [0.02, 2.56], p = 0.22). A larger decrease in the platelet count and blood glucose levels, and larger increase in creatinine and sodium levels within the first 7 days of hospital admission were each independent predictors of 28-day mortality (p < 0.05).
In this study of hospitalized patients with COVID-19, while the outcomes of COVID illness severity, odds of mortality, and chance of respiratory failure were better in the Aggrenox group compared to standard of care alone, the data did not reach statistical significance to support the standard use of adjuvant Aggrenox in such patients.
2019 年冠状病毒病（COVID-19）是一种免疫炎症和高凝状态，可导致呼吸窘迫、多器官功能障碍和死亡。双嘧达莫通过增加细胞外腺苷，据推测通过其免疫抑制、抗炎、抗栓、血管扩张和抗病毒作用，对 COVID-19 患者具有保护作用。同样，小剂量阿司匹林也显示出对 COVID-19 患者的保护作用。本研究评估了这两种药物联合制成的 Aggrenox（双嘧达莫 ER 200mg/阿司匹林 25mg 口服/经口）在住院 COVID-19 患者中的疗效。
在一项开放标签、单中心随机对照试验（RCT）中，住院的 COVID-19 患者被分配接受辅助 Aggrenox（双嘧达莫 ER 200mg/阿司匹林 25mg 口服/经口）与标准治疗相比，与单独标准治疗。主要终点是根据八点 COVID 序数量表的变化评估疾病严重程度，分数为 1 至 8，分数越高表示病情越严重。次要终点包括全因死亡率和呼吸衰竭。通过第 14、28 天和/或出院来衡量结果。
从 2020 年 10 月 1 日至 2021 年 4 月 30 日，共有 98 名患者入组，中位[IQR]年龄为 57[47,62]岁，53.1%（n=52）为女性，随机分为两组（n=49 例 Aggrenox 加标准治疗与 n=49 例标准治疗）。在第 14 天和第 28 天，接受辅助 Aggrenox 治疗的患者与对照组相比，在疾病严重程度（COVID 序数量表）方面没有发现有临床意义的差异。第 28 天的总死亡率在 Aggrenox 组为 6.1%（3 例，n=49），对照组为 10.2%（5 例，n=49）（OR[95%CI]：0.40[0.04,4.01]，p=0.44）。第 28 天发生呼吸衰竭的患者在 Aggrenox 组为 4（8.3%，n=48），对照组为 7（14.6%，n=48）（OR[95%CI]：0.21[0.02,2.56]，p=0.22）。入院后 7 天内血小板计数和血糖水平下降更大，肌酐和钠水平升高更大，是 28 天死亡率的独立预测因素（p<0.05）。
在这项对 COVID-19 住院患者的研究中，与单独标准治疗相比，Aggrenox 组的 COVID 疾病严重程度、死亡率和呼吸衰竭几率的结果更好，但数据没有达到统计学意义，无法支持在这类患者中常规使用辅助性 Aggrenox。
