Losartan arb
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Summary
10 papers analyzed
These studies suggest losartan is effective in reducing heart failure-related outcomes and postimplant calcification, but shows limited impact on COVID-19, COPD, HIV inflammation, and certain cardiac conditions, with potential cognitive benefits in Alzheimer's disease.
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Losartan as an Angiotensin Receptor Blocker (ARB): Clinical Insights and Applications
High-Dose vs. Low-Dose Losartan in Heart Failure
Clinical Outcomes in Heart Failure Patients
The HEAAL study explored the effects of high-dose (150 mg) versus low-dose (50 mg) losartan on clinical outcomes in patients with heart failure. The study found that high-dose losartan significantly reduced the rate of death or admission for heart failure compared to the low-dose group. Specifically, 43% of patients in the high-dose group experienced these outcomes versus 46% in the low-dose group, indicating a hazard ratio (HR) of 0.90. However, higher doses were associated with increased renal impairment, hypotension, and hyperkalemia, although these adverse events did not lead to significantly more treatment discontinuations.
Losartan in COVID-19 Treatment
Impact on Mild Hypoxemia in COVID-19 Patients
A randomized prospective study investigated the addition of losartan to the standard of care in hospitalized COVID-19 patients with mild hypoxemia. The study concluded that losartan did not significantly impact clinical outcomes such as the need for mechanical ventilation or death before ventilation. This suggests that losartan may not provide additional benefits in the early stages of COVID-19 infection.
Losartan for Pulmonary Emphysema
Efficacy in COPD Patients
A multicenter randomized placebo-controlled trial evaluated losartan's efficacy in reducing emphysema progression in COPD patients. The study found no significant difference in emphysema progression between the losartan and placebo groups over 48 weeks. This indicates that losartan may not be effective in preventing emphysema progression in COPD patients.
Losartan in HIV-Associated Inflammation and Fibrosis
Effects on Inflammation and Immune Recovery
A randomized placebo-controlled trial assessed losartan's impact on inflammation and immune recovery in older persons with HIV. The study found that losartan did not significantly improve blood measures of inflammation, immune activation, or T-cell recovery compared to placebo. This suggests that losartan may not reduce inflammation-associated comorbidities in this population beyond its blood pressure-lowering effects.
Losartan and Bioprosthetic Valve Calcification
Anticalcification Effects
Research on a rabbit model demonstrated that losartan significantly attenuates calcification of bioprosthetic heart valve leaflets. The study showed reduced calcium levels and suppressed expression of calcification-related proteins such as IL-6, osteopontin, and BMP-2 in the losartan-treated group. These findings suggest potential benefits of losartan in reducing structural valve deterioration.
Losartan in Non-Alcoholic Steatohepatitis (NASH)
Anti-Fibrotic Properties
A randomized controlled trial aimed to assess losartan's anti-fibrotic effects in patients with NASH. The study faced recruitment challenges and was unable to determine a significant impact due to insufficient sample size. However, the trial highlighted the difficulty in recruiting patients not already on ARB or ACE inhibitor therapy.
Cognitive and Cerebrovascular Benefits in Alzheimer's Disease
Mechanisms of Action
A study on a mouse model of Alzheimer's disease identified that losartan's cognitive and cerebrovascular benefits are mediated through the angiotensin IV receptor (AT4R). The study found that blocking AT4R countered losartan's positive effects on spatial learning, memory, and cerebrovascular function, suggesting that AT4R activation is crucial for these benefits.
Losartan Metabolite EXP3179
Unique Vasoactive Properties
Research on losartan's metabolite, EXP3179, revealed that it possesses unique endothelium-dependent vasoactive properties. Unlike its counterpart EXP3174, EXP3179 can fully block AT1R signaling and significantly decrease blood pressure while enhancing endothelial function. This indicates that losartan's therapeutic effects may be more complex than previously understood.
Losartan in Right Ventricular Dysfunction
Effects in Tetralogy of Fallot Patients
The REDEFINE trial investigated losartan's impact on right ventricular (RV) dysfunction in adults with repaired tetralogy of Fallot. The study found no significant improvement in RV ejection fraction or secondary outcomes such as left ventricular function and exercise capacity. This suggests that losartan may not be effective in treating RV dysfunction in this patient population.
Losartan/Hydrochlorothiazide Combination Therapy
Efficacy in Uncontrolled Hypertension
The KAHT-Trial compared the efficacy of losartan/hydrochlorothiazide (Los/HCTZ) combination therapy to high-dose ARB in patients with uncontrolled hypertension. Both treatments significantly reduced blood pressure over one year, with no significant differences between the groups. This indicates that Los/HCTZ combination therapy is effective and well-tolerated in managing uncontrolled hypertension.
Conclusion
Losartan, as an angiotensin receptor blocker, has demonstrated varied efficacy across different clinical conditions. While high-dose losartan shows promise in heart failure management, its benefits in other conditions such as COVID-19, COPD, and HIV-associated inflammation are less clear. Further research is needed to fully understand losartan's potential in these and other therapeutic areas.
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