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1.
JAMA Netw Open ; 5(3): e222735, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1748801

ABSTRACT

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Design, Setting, and Participants: This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. Main Outcomes and Measures: The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants. Results: A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). Conclusions and Relevance: This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve Pao2:Fio2 ratio at 7 days. These data may have implications for ongoing clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04312009.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Losartan/therapeutic use , Lung Injury/prevention & control , Lung Injury/virology , Adult , Aged , COVID-19/diagnosis , Double-Blind Method , Female , Hospitalization , Humans , Lung Injury/diagnosis , Male , Middle Aged , Organ Dysfunction Scores , Respiratory Function Tests , United States
2.
BMC Cardiovasc Disord ; 22(1): 116, 2022 03 19.
Article in English | MEDLINE | ID: covidwho-1745515

ABSTRACT

BACKGROUND: One of the global problems is to control the coronavirus epidemic, and the role of different medicines is still unknown to policymakers. This study was conducted to evaluate the effects of losartan on the mortality rate of COVID-19 in hypertensive patients. METHODS: The research sample of analytical study included 1458 patients presenting to COVID-19 diagnostic centers in Yazd that were examined in the first six months of 2020. Data were analyzed using descriptive statistics as well as chi-square, Fisher's exact test, t test, and logistic regression. RESULTS: Of 1458 subjects that were studied, 280 were hypertensive of whom 179 tested positive for SARS-CoV-2 PCR. The results showed a lower chance of death by more than 5 times in hypertensive patients who used losartan (P = 0.003). Moreover, regarding the effect of losartan on the prevention of COVID-19 in hypertensive patients, it was found that this medicine played a protective role although this relationship was not statistically significant (P = 0.86). CONCLUSIONS: The results showed that losartan reduced the chance of mortality in hypertensive patients. It is recommended that the effect of losartan and other blood pressure medicines on COVID-19 patients be investigated in larger studies as well as laboratory investigations.


Subject(s)
COVID-19 , Hypertension , Antihypertensive Agents/therapeutic use , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Losartan/therapeutic use , SARS-CoV-2
3.
Sci Rep ; 11(1): 24397, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1585779

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) is an important factor in coronavirus disease (COVID-19) interactions. Losartan (LOS) belongs to the angiotensin receptor blocker (ARB) family. Additionally, the protective role of ACE2 restored by LOS has been suggested and clinically examined in the treatment of COVID-19 patients. Furthermore, clinical trials with LOS have been conducted. However, the mechanism through which LOS enhances ACE2 expression remains unclear. In addition, the response of ACE2 to LOS differs among patients. Our LOS-treated patient data revealed a correlated mechanism of ACE2 with components of the renin-angiotensinogen system. We observed a significant positive regulation of MAS1 and ACE2 expression. In the context of LOS treatment of COVID-19, ACE2 expression could depend on LOS regulated MAS1. Thus, MAS1 expression could predict the COVID-19 treatment response of LOS.


Subject(s)
Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme 2/metabolism , Losartan/pharmacology , Renin-Angiotensin System/drug effects , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2/genetics , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Databases, Factual , Humans , Losartan/therapeutic use , /metabolism , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , SARS-CoV-2/isolation & purification , Up-Regulation/drug effects
6.
Int J Clin Pract ; 75(6): e14124, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1132932

ABSTRACT

BACKGROUND: Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID-19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID-19. METHODS: In this randomised clinical trial, hospitalised patients with COVID-19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30-day mortality rate and length of hospital stay. RESULTS: The mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30-day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241). CONCLUSIONS: There was no priority in losartan or amlodipine administration in COVID-19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first-line anti-HTN medications in COVID-19.


Subject(s)
COVID-19 , Hypertension , Aged , Aged, 80 and over , Amlodipine/therapeutic use , Antihypertensive Agents/therapeutic use , Blood Pressure , Double-Blind Method , Humans , Hypertension/drug therapy , Losartan/pharmacology , Losartan/therapeutic use , Middle Aged , SARS-CoV-2 , Treatment Outcome
7.
PLoS One ; 15(12): e0244708, 2020.
Article in English | MEDLINE | ID: covidwho-999851

ABSTRACT

BACKGROUND: Retrospective studies on the use of Renin-Angiotensin-Aldosterone System blockade in patients with Coronavirus Disease 2019 (COVID-19) have been informative but conflicting, and prospective studies are required to demonstrate the safety, tolerability, and outcomes of initiating these agents in hospitalized patients with COVID-19 and hypertension. METHODS AND FINDINGS: This is a single center feasibility study encompassing two cohorts: (1) prospective cohort (April 21, 2020 to May 29, 2020) and (2) retrospective cohort (March 7, 2020 to April 1, 2020) of hospitalized patients with real-time polymerase chain reaction (PCR) positive SARS-CoV-2 by nasopharyngeal swab. Key inclusion criteria include BP > 130/80 and a requirement of supplemental oxygen with FiO2 of 25% or higher to maintain SpO2 > 92%. Key exclusion criteria included hyperkalemia and acute kidney injury (AKI) at the time of enrollment. Prospective cohort consisted of de novo initiation of losartan and continuation for a minimum of 7 days and assessed for adverse events (AKI, hyperkalemia, transaminitis, hypotension) and clinical outcomes (change in SpO2/FiO2 and inflammatory markers, need for ICU admission and mechanical ventilation). Retrospective cohort consisted of continuation of losartan (prior-to-hospitalization) and assessment of similar outcomes. In the prospective cohort, a total of 250 hospitalized patients were screened and inclusion/exclusion criteria were met in 16/250 patients and in the retrospective cohort, a total of 317 hospitalized patients were screened and inclusion/exclusion criteria were met in 14/317 patients. Most common adverse event was hypotension, leading to discontinuation in 3/16 (19%) and 2/14 (14%) patients in the prospective and retrospective cohort. No patients developed AKI in the prospective cohort as compared to 1/14 (7%) patients in the retrospective cohort, requiring discontinuation of losartan. Hyperkalemia occurred in 1/16 (6%) and 0/14 patients in the prospective and retrospective cohorts, respectively. In the prospective cohort, 3/16 (19%) and 2/16 (13%) patients required ICU admission and mechanical ventilation. In comparison, 3/14 (21%) required ICU admission and mechanical ventilation in the retrospective cohort. A majority of patients in both cohorts (14/16 (88%) and 13/14 (93%) patients from the prospective and retrospective cohort) were discharged alive from the hospital. A total of 9/16 (prospective) and 5/14 (retrospective) patients completed a minimum 7 days of losartan. In these 9 patients in the prospective cohort, a significant improvement in SpO2/FiO2 ratio was observed from day 1 to 7. No significant changes in inflammatory markers (initiation, peak, and day 7) were observed in either cohort. CONCLUSION: In this pilot study we demonstrate that losartan was well-tolerated among hospitalized patients with COVID-19 and hypertension. We also demonstrate the feasibility of patient recruitment and the appropriate parameters to assess the outcomes and safety of losartan initiation or continuation, which provides a framework for future randomized clinical trials.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , COVID-19/pathology , Hypertension/drug therapy , Losartan/therapeutic use , Aged , Angiotensin II Type 1 Receptor Blockers/adverse effects , Blood Pressure/drug effects , Female , Humans , Losartan/adverse effects , Male , Middle Aged , Pilot Projects , Prospective Studies , Retrospective Studies , SARS-CoV-2
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