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Clinical outcome of renin-angiotensin-aldosterone system blockers in treatment of hypertensive patients with COVID-19: a systematic review and meta-analysis.

ABSTRACT:

Background

Novel coronavirus disease 2019 has been stated as global disease pandemic due to its rapid spread worldwide. Up to 30% of coronavirus disease 2019 patients with hypertension are more susceptible to death. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been used as primary line of medication for hypertension; nonetheless, conflicting data arises as numerous studies showed contradictory results.

Main body

Aiming to show clinical outcome of renin-angiotensin-aldosterone system blockers in hospital treatment of hypertensive patients with coronavirus disease 2019, systematically searched literatures through five databases were intensively appraised using The Grading of Recommendations Assessment, Development and Evaluation checklists for cohort studies. Based on the result evaluation from retrospective cohorts involving more than 15,000 patients across Asia and other regions of the world, ten encompassed studies divided into two subgroups in this meta-review showed that in-hospital hypertensive coronavirus disease 2019 patients receiving antihypertensive drugs were associated with overall risk reduction in subgroup 1 (hazard ratio, HR = 0.96, 95% CI = 0.82-1.12) to no outcome association of all-cause mortalities in subgroup 2 (HR = 0.26, 95% CI = 0.19-0.34). All appraised studies in synergism showed that mortality outcomes were not augmented with the employment of either ACE inhibitor or ARB in subjects.

Conclusion

Therefore, the results support recommendation by the American Heart Association not to discontinue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker regimens in coronavirus disease 2019 patients with hypertension.

SUBMITTER: Laurentius A

PROVIDER: S-EPMC7863036 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundA potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.MethodsWe carried out a population-based case-control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients' clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.ResultsAmong both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.ConclusionsIn this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

Project description:Background and aimsCoronavirus disease 2019 (COVID-19) has been observed to cause a high mortality in people with cardiometabolic diseases. Renin-angiotensin-aldosterone system (RAAS) blockers enhance the expression of ACE2, the binding receptor of SARS-CoV-2, and can enhance viral infectivity. We aim to provide a pooled estimate of the effect of RAAS blockers on COVID-19 outcomes.MethodsA literature search was performed using MEDLINE/PubMed, Google Scholar and preprint servers. All clinical studies analyzing the effect of RAAS blockers on clinical outcomes in COVID-19 patients were included in this study. Newcastle-Ottawa scale was used for quality assessment of studies. MOOSE checklist was followed. Mortality and severity outcomes were recorded as pooled odds ratio (OR) with 95% Confidence Intervals (CIs) and level of heterogeneity (I 2). Odds of mortality was the primary outcome. Odds of severity, hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV), steroid use and acute kidney injury were the secondary outcomes. Severity outcomes were chosen depending upon the definition used by respective authors. Country-specific variations and effects of individual class of RAAS blockers were also explored.ResultsIn total 47 published studies were included in the final analysis, with a total of 26,432 patients from 31 studies in mortality analysis and 20,127 patients from 23 studies in severity analysis. No increased risk of mortality [Pooled OR 0.91 (0.65-1.26), I 2 = 89%] or severity [Pooled OR 1.08 (0.79-1.46), I 2 = 88%] was seen with RAAS blockers. The drug class was protective in hypertension [pooled OR 0.63 (0.46-0.86), I 2 = 58%]. Severity of COVID-19 outcomes was high for Europeans [Pooled OR 2.08 (1.52-2.85), I 2 = 77%] and US patients [Pooled OR 1.87 (1.62-2.17)]. Nearly 4 times higher risk of hospitalization and 2 times higher risk of ICU admission and MV were observed in US patients. Class-wise, angiotensin receptor blocker use was associated with 1.6 times higher odds of severity, mainly in Europeans.ConclusionRAAS blockers are not associated with increased mortality in COVID-19 patients and should be continued in hypertensives. US and European patients are at higher risk of severe outcomes. Pharmacogenetic differences may explain the ethnicity-related variations.Plain language summaryEffect of RAAS-blocking medicines on COVID-19 Background and aims: Higher deaths have been observed in COVID-19 patients who have other long-term diseases such as heart disease, diabetes, and high blood pressure. Many of these patients are prescribed a class of medicines called RAAS blockers (ramipril, telmisartan, etc). We studied whether the use of these medicines worsens the course of COVID-19 disease in these patients or causes excess deaths.Methods: We conducted a pooled analysis of 47 observational studies on the use of RAAS blocker drugs in COVID-19 patients.Results: We found that RAAS blockers do not cause excess deaths in patients with COVID-19. On the contrary, they have benefits if prescribed to those with high blood pressure. We also found that whereas European and US patients of COVID-19 taking these medicines had higher disease severity, this was not the case for Chinese patients.Conclusion: Theremay be some genetic and other factors responsible for differences by ethnicity.