The Wolfson Centre for Personalized Medicine, MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GL, UK.
Department of Biostatistics, Institute of Population Health Sciences, University of Liverpool, Liverpool, L69 3GL, UK.
Br J Clin Pharmacol. 2021 Dec;87(12):4534-4545. doi: 10.1111/bcp.14927. Epub 2021 Jul 7.
The aim of this study was to continually evaluate the association between cardiovascular drug exposure and COVID-19 clinical outcomes (susceptibility to infection, disease severity, hospitalization, hospitalization length, and all-cause mortality) in patients at risk of/with confirmed COVID-19.
Eligible publications were identified from more than 500 databases on 1 November 2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer.
Of 52 735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most-reported drugs were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with confirmed COVID-19 infection (OR 1.14, 95% CI 1.00-1.31). Among COVID-19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 95% CI 1.34-2.32), disease severity (OR 1.40, 95% CI 1.26-1.55) and all-cause mortality (OR 1.22, 95% CI 1.12-1.33) but not hospitalization length (mean difference -0.27, 95% CI -1.36-0.82 days). After adjustment, ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.92, 95% CI 0.71-1.19), hospitalization (OR 0.93, 95% CI 0.70-1.24), disease severity (OR 1.05, 95% CI 0.81-1.38) or all-cause mortality (OR 0.84, 95% CI 0.70-1.00). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.93, 95% CI 0.79-1.09), hospitalization (OR 0.84, 95% CI 0.58-1.22), hospitalization length (mean difference -0.14, 95% CI -1.65-1.36 days), disease severity (OR 0.92, 95% CI 0.76-1.11) while it decreased the odds of dying (OR 0.76, 95% CI 0.65-0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias.
Cardiovascular drugs are not associated with poor COVID-19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.
本研究旨在持续评估心血管药物暴露与确诊 COVID-19 患者(感染易感性、疾病严重程度、住院、住院时间和全因死亡率)的 COVID-19 临床结局之间的关联。
于 2020 年 11 月 1 日,从 500 多个数据库中确定了合格的文献。一位评审员独立提取了 20%的记录,由第二位评审员进行评估。
在 52735 份筛选记录中,429 项研究和 390 项研究分别纳入定性和定量综合分析。报告最多的药物是血管紧张素转换酶抑制剂(ACEI)/血管紧张素受体阻滞剂(ARB),ACEI/ARB 暴露与确诊 COVID-19 感染呈边缘关联(OR 1.14,95%CI 1.00-1.31)。在 COVID-19 患者中,未调整的估计表明,ACEI/ARB 暴露与住院(OR 1.76,95%CI 1.34-2.32)、疾病严重程度(OR 1.40,95%CI 1.26-1.55)和全因死亡率(OR 1.22,95%CI 1.12-1.33)相关,但与住院时间无关(平均差异-0.27,95%CI-1.36-0.82 天)。调整后,ACEI/ARB 暴露与确诊 COVID-19 感染(OR 0.92,95%CI 0.71-1.19)、住院(OR 0.93,95%CI 0.70-1.24)、疾病严重程度(OR 1.05,95%CI 0.81-1.38)或全因死亡率(OR 0.84,95%CI 0.70-1.00)无关。同样,仅涉及高血压患者的亚组分析显示,ACEI/ARB 暴露与确诊 COVID-19 感染(OR 0.93,95%CI 0.79-1.09)、住院(OR 0.84,95%CI 0.58-1.22)、住院时间(平均差异-0.14,95%CI-1.65-1.36 天)、疾病严重程度(OR 0.92,95%CI 0.76-1.11)无关,而降低了死亡风险(OR 0.76,95%CI 0.65-0.88)。其他心血管药物也呈现出类似的趋势。然而,由于存在高度异质性和严重的偏倚风险,这些发现的有效性受到限制。
在调整分析中,心血管药物与 COVID-19 不良结局无关。患者应继续按规定服用这些药物。