Abdulhak, Aref A. Bin

Background: SARS-CoV-2 infects its target cells via angiotensin converting enzyme 2 receptor, a membrane-bound protein found on the surface of many human cells. Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptors blockers (ARB) has been shown to increase angiotensin converting enzyme 2 expression by up to 5-fold. Areas of uncertainty: These findings coupled with observations of the high prevalence and mortality among SARS-CoV-2-infected patients with underlying cardiovascular disease have led to a speculation that ACEIs/ARBs may predispose to higher risk of being infected with SARS-CoV-2. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and the risk of SARS-CoV-2 infection or hospitalization due to COVID-19 disease. Data sources: We searched Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Medrxiv.org preprint server until June 18, 2020. Therapeutic advances: Ten studies (6 cohorts and 4 case control) that enrolled a total of 23,892 patients and 853,369 controls were eligible for inclusion in our meta-analysis. One study was excluded from the analysis because of high risk of bias. Prior use of ACEIs was not associated with an increased risk of acquiring SARS-CoV-2 or hospitalization due to COVID-19 disease, odds ratio 0.98, 95% confidence interval (0.91–1.05), I2 = 15%. Similarly, prior use of ARBs was not associated with an increased risk of acquiring SARS-CoV-2, odds ratio 1.04, 95% confidence interval (0.98–1.10), I2 = 0%. Conclusion: Cumulative evidence suggests that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19 or hospitalization due to COVID-19 disease. Our results provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs because of fear of COVID-19.

Background: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known to increase the expression of angiotensin converting enzyme 2 receptor, which has been shown to be the receptor for the acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Areas of Uncertainty: Based on these observations, speculations raised the concerns that ACEIs/ARBs users would be more susceptible to SARS-CoV-2 infection and would be at higher risk for severe COVID-19 disease and death. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and mortality due to COVID-19 disease. Data Sources: A comprehensive search of several databases from November 2019 to June 18, 2020 was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus. Medrxiv.org was also searched for unpublished data. Therapeutic Advances: Nine studies with a total of 18,833 patients infected with SARS-CoV-2 met our eligibility criteria. Prior use of ACEIs and/or ARBs was associated with reduced mortality among SARS-CoV-2-infected patients, with a pooled adjusted relative risk (aRR) from 6 studies of 0.63, 95% confidence interval (CI) (0.42–0.94) (I 2 = 65%). Three studies reported separately on ACEIs or ARBs and their association with survival among SARS-CoV-2-infected patients, with a pooled adjusted relative risk of 0.78, 95% CI (0.58–1.04) (I 2 = 0%) and 0.97, 95% CI (0.73–1.30) (I 2 = 0%) respectively. The results of sensitivity analyses were consistent with the main analysis. Conclusion: Our meta-analysis suggests that use of ACEIs/ARBs is associated with a decreased risk of death among SARS-CoV-2-infected patients. This finding provides a reassurance to the public not to stop prescribed ACEIs/ARBs because of fear of severe COVID-19.

Abstract Importance:SARS-CoV-2 virus gains access and infects target cells via angiotensin converting enzyme 2 (ACE2) receptor. Because angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) could increase the expression of ACE2, there are growing concerns that their use could increase the risk of SARS-CoV-2 infection. Cardiac societies have called for epidemiological research about this emerging controversy. Objective:We sought to systematically review the literature and perform a meta-analysis about prior use of ACEI/ARBs and risk of SARS-CoV-2 infection.Data source:We searched multiple data sources including PubMed , ClinicalTrial.org , and medrxiv.org from November 2019 through May 16, 2020. Study selection:Any study that reported on the adjusted association of prior use of ACEIs / ARBs and risk of acquiring SARS-CoV-2 infection was eligible. Two authors independently reviewed eligible studies and extracted data into a prespecified data collection form. Data synthesis:An inverse variance meta-analytic approach was used to pool adjusted odds ratios using a random effect model meta-analysis. I2 test was used to assess in-between studies heterogeneity. The Newcastle–Ottawa quality assessment scale (NOS) was used to assess the quality of included studies. Main outcome and Measures:The association between the prior use of ACEIs or ARBs and risk of SARS-CoV-2 infection was assessed using pooled OR and 95% confidence interval. Results:Six case control studies that enrolled a total of 5657 patients (2536 patients in ACEIs arm and 3121 patients in ARBs arm ) and 721,859 controls were included in our meta-analysis. Two of the included studies were from the USA, one from Italy, one from China, one from Spain, and one from South Korea. All included studies scored high based on NOS scale. Prior use of ACEIs was not significantly associated with an increased risk of SARS-CoV-2 infection, OR 0.93, CI (0.85,1.02), I2=20%. Similarly, prior use of ARBs was not significantly associated with an increased risk of SARS-CoV-2 infection, OR 0.86, CI (0.67,1.10), I2=93%. Sensitivity analysis was performed by removing a study that could have been affected by residual confounding; OR for ARB 1.04, CI (0.96,1.12), I2=32%.Conclusion:Findings from this systematic review and meta-analysis suggest that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19. Our results are in support of the recent recommendations of cardiac societies and provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs due to fear of COVID-19.

Purpose: In aortic stenosis patients referred for surgical and transcatheter aortic valve replacement (AVR), the evidence of diagnostic accuracy of coronary computed tomography angiography (CCTA) has been limited. The objective of this study was to investigate the diagnostic accuracy of CCTA for significant coronary artery disease (CAD) in patients referred for AVR using invasive coronary angiography (ICA) as the gold standard. Materials and Methods: We searched databases for all diagnostic studies of CCTA in patients referred for AVR, which reported diagnostic testing characteristics on patient-based analysis required to pool summary sensitivity, specificity, positive-likelihood ratio, and negative-likelihood ratio. Significant CAD in both CCTA and ICA was defined by >50% stenosis in any coronary artery, coronary stent, or bypass graft. Results: Thirteen studies evaluated 1498 patients (mean age, 74 y; 47% men; 76% transcatheter AVR). The pooled prevalence of significant stenosis determined by ICA was 43%. Hierarchical summary receiver-operating characteristic analysis demonstrated a summary area under curve of 0.96. The pooled sensitivity, specificity, and positive-likelihood and negative-likelihood ratios of CCTA in identifying significant stenosis determined by ICA were 95%, 79%, 4.48, and 0.06, respectively. In subgroup analysis, the diagnostic profiles of CCTA were comparable between surgical and transcatheter AVR. Conclusions: Despite the higher prevalence of significant CAD in patients with aortic stenosis than with other valvular heart diseases, our meta-analysis has shown that CCTA has a suitable diagnostic accuracy profile as a gatekeeper test for ICA. Our study illustrates a need for further study of the potential role of CCTA in preoperative planning for AVR.