UNASSIGNED: Cardioprotective drugs have not been previously shown to improve the prognosis in patients with fulminant myocarditis presentation (FMP). We aimed to investigate whether cardioprotective drugs, including angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) and β-blocker, administered during hospitalization improved the prognosis in patients with FMP.
UNASSIGNED: This multicenter cohort study conducted in Japan included 755 patients with clinically diagnosed FMP. Those who died within 14 days of admission were excluded, and 588 patients (median age 53 [37-65] years and 40% female) were evaluated. The primary outcome was the composite of 90-day mortality or heart transplantation. The patients were divided into 4 groups according to whether they were administered ACEI/ARB or β-blocker during hospitalization. Administration of ACEI/ARB without β-blocker improved the overall patient outcomes (log-rank test [vs. ACEI/ARB - and β-blocker -]: ACEI/ARB + and β-blocker -, P<0.001; ACEI/ARB - and β-blocker +, P=0.256). Subsequently, a matched cohort of 146 patient pairs was generated for patients with or without ACEI/ARB administration during hospitalization. The outcome-free survival at 90 days was significantly higher in the ACEI/ARB administration group than in the non-administration group (hazard ratio 0.37; 95% confidence interval 0.19-0.71).
UNASSIGNED: Administration of ACEI or ARB during hospitalization was associated with favorable outcomes in terms of 90-day mortality and heart transplantation events in patients with clinically diagnosed FMP.

Angiotensin II receptor blockers (ARBs) are contraindicated during pregnancy because of fetal toxicity. All previous reports on adverse fetal outcomes involved women who continued to take low-dose ARBs for hypertension and were unaware of the adverse effects. Herein, we report the case of a 23-year-old pregnant woman in her third trimester who experienced an ARB overdose after an argument with her partner. Pregnancy was complicated by transient oligohydramnios, and fetal magnetic resonance imaging suggested renal failure. Despite these concerns, the newborn had no morphological abnormalities or abnormal neurological findings. Renal impairment improved over time, and the infant grew well. A single overdose of ARBs in the third trimester can lead to fetal renal failure, similar to long-term low-dose ARB administration; however, favorable outcomes are possible. An overdose of ARBs may transiently cause renal failure, which may improve. The study findings may inform counseling for women who are unexpectedly exposed to an overdose of ARBs.

OBJECTIVE: Although sodium glucose cotransporter2 inhibitor (SGLT-2I) is widely used in clinical practice, sufficient renin-angiotensin system (RAS) inhibition remains the cornerstone of diabetic kidney disease (DKD) treatment. The aim of this single-center study was to evaluate the efficacy and safety of dual RAS blockade compared with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) monotherapy in non-elderly DKD patients with preserved eGFR (WHO Standard, < 60y).
METHODS: This single-center study was registered in Chinese Clinical Trial Registry (ChiCTR1900024752), and approved by the ethical committee (KY201994). In this study, we recruited non-elderly type 2 diabetes volunteers with initial diagnosis of DKD to receive dual RAS blockade or monotherapy. 150 non-elderly DKD patients with preserved eGFR were recruited. The patients were randomly divided into dual RAS blockade group and monotherapy group. The dual RAS blockade group treatment regimen was an 80 mg valsartan plus a 4 mg perindopril tert-butylamine per day. At the same time, monotherapy group patients who received the 8 mg perindopril tert-butylamine or 160 mg valsartan monotherapy. The clinical data of the three groups were compared at baseline and collected during the follow-up period of 12 months.
RESULTS: The baseline of patients who received dual RAS blockade was similar to that of monotherapy group. After 12 months of treatment, the median level of proteinuria in the dual RAS blockade group was significantly lower than that in the monotherapy group. There was no significant difference in the estimated glomerular filtration rate (eGFR) level, potassium, blood pressure and no serious adverse reactions.
CONCLUSIONS: In non-elderly DKD patients with preserved eGFR, dual RAS blockade is superior to control proteinuria, and does not increase the probability of adverse reactions such as hyperkalemia, hypotension and acute kidney injury in 12 months.

It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688-0.571; 0.696, 0.439-1.103; 1.056, 0.941-1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613-2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745-1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities.

UNASSIGNED: Angiotensin II receptor blockers (ARBs) have been associated with preventing posttraumatic stress disorder symptom development and improving memory. However, the underlying neural mechanisms are poorly understood. This study investigated ARB effects on memory encoding and hippocampal functioning that have previously been implicated in posttraumatic stress disorder development.
UNASSIGNED: In a double-blind randomized design, 40 high-trait-anxious participants (33 women) received the ARB losartan (50 mg) or placebo. At drug peak level, participants encoded images of animals and landscapes before undergoing functional magnetic resonance imaging, where they viewed the encoded familiar images and unseen novel images to be memorized and classified as animals/landscapes. Memory recognition was assessed 1 hour after functional magnetic resonance imaging. To analyze neural effects, whole-brain analysis, hippocampus region-of-interest analysis, and exploratory multivariate pattern similarity analysis were employed.
UNASSIGNED: ARBs facilitated parahippocampal processing. In the whole-brain analysis, losartan enhanced brain activity for familiar images in the parahippocampal gyrus (PHC), anterior cingulate cortex, and caudate. For novel images, losartan enhanced brain activity in the PHC only. Pattern similarity analysis showed that losartan increased neural stability in the PHC when processing novel and familiar images. However, there were no drug effects on memory recognition or hippocampal activation.
UNASSIGNED: Given that the hippocampus receives major input from the PHC, our findings suggest that ARBs may modulate higher-order visual processing through parahippocampal involvement, potentially preserving intact memory input. Future research needs to directly investigate whether this effect may underlie the preventive effects of ARBs in the development of posttraumatic stress disorder.

Losartan is a widely prescribed angiotensin II receptor blocker (ARB) used for the management of hypertension and various cardiovascular conditions. While it is generally considered a safe medication, rare cases of hepatotoxicity have been reported in the literature. We present a case of severe hepatic injury and sub-fulminant hepatitis attributed to losartan use in a 54-year-old male patient with underlying hypertension. He presented with a two-week history of abdominal pain, progressive jaundice, dark urine, and vomiting, followed by altered sensorium. His clinical picture, serology, and imaging findings confirmed a severe hepatic injury. After ruling out all possible causes, he was diagnosed with drug-induced hepatotoxicity with losartan treatment. He started improving gradually after losartan discontinuation, N-acetylcysteine administration, and supportive management with close monitoring of liver enzymes. This case report aims to underscore the importance of recognizing losartan as one of the potential causes of hepatotoxicity.

BACKGROUND: Keloid is a skin disorder that results from excessive fibrous tissue growth in the area of the initial trauma. Treating keloids can be challenging since the success of various treatments varies from one study to another. Triamcinolone acetonide injection, a standard treatment, can cause undesirable side effects. Meanwhile, the effectiveness of existing topical therapies for keloids is not always reliable. The pro-inflammatory, pro-proliferative, and pro-fibrotic effects of angiotensin II in human skin contribute to keloid formation. Losartan potassium, an angiotensin II blocker, has the potential to act as an anti-keloid agent. Due to the thicker skin structure of a keloid and ease of application, ethosome gel is chosen as a safe and comfortable carrier for losartan potassium, making it a good choice for treating keloids.
METHODS: In this randomised clinical trial, 46 adults with keloids were divided into two treatment groups. One group of 23 participants received 5% losartan potassium loaded in ethosomal gel, while the other group of 23 participants received intralesional injections of 10% triamcinolone acetonide. Over 12 weeks, changes in POSAS 3.0 scores, degree of erythema and pigmentation, surface area, thickness, and pliability of the keloids will be measured at four different times: baseline, 4 weeks, 8 weeks, and 12 weeks. Statistical analysis will be conducted using SPSS software version 24, with a significance level of p < 0.05.
CONCLUSIONS: Losartan potassium is believed to be beneficial for keloid management because it inhibits the angiotensin II receptor, which plays a role in inflammation, proliferation, and fibrosis. This study examines the efficacy of 5% losartan potassium loaded in ethosomal gel for human keloids.
BACKGROUND: Clinicaltrial.gov identifier NCT05893108 . Registered on 7 June 2023.

Risk mitigation for most teratogenic medications relies on risk communication via drug label, and prenatal exposures remain common. Information on the types of and risk factors for prenatal exposures to medications with teratogenic risk can guide strategies to reduce exposure.
This study aimed to identify medications with known or potential teratogenic risk commonly used during pregnancy among privately insured persons.
We used the Merative™ MarketScan® Commercial Database to identify pregnancies with live or nonlive (ectopic pregnancies, spontaneous and elective abortions, stillbirths) outcomes among persons aged 12 to 55 years from 2011 to 2018. Start/end dates of medication exposure and pregnancy outcomes were identified via an adapted algorithm based on validation studies. We required continuous health plan enrollment from 90 days before conception until 30 days after the pregnancy end date. Medications with known or potential teratogenic risk were selected from TERIS (Teratogen Information System) and drug monographs based on the level of risk and quality of evidence (138 with known and 60 with potential risk). We defined prenatal exposure on the basis of ≥1 outpatient pharmacy claim or medical encounter for medication administration during target pregnancy periods considering medication risk profiles (eg, risk only in the first trimester or at a certain dose threshold). Sex hormones and hormone analogs, and abortion and postpartum/abortion hemorrhage treatments were not considered as teratogenic medications because of challenges in separating pregnancy-related indications, nor were opioids (because of complex risk-benefit considerations) or antiobesity medications if their only teratogenic mechanism was weight loss.
Among all pregnancies, the 10 medications with known teratogenic risk and the highest prenatal exposures were sulfamethoxazole/trimethoprim (1988 per 100,000 pregnancy-years), high-dose fluconazole (1248), topiramate (351), lisinopril (144), warfarin (57), losartan (56), carbamazepine (50), valproate (49), vedolizumab (28 since 2015), and valsartan (25). Prevalence of exposure to sulfamethoxazole/trimethoprim decreased from 2346 to 1453 per 100,000 pregnancy-years from 2011 to 2018, but prevalence of exposure to vedolizumab increased 6-fold since its approval in 2015. Prenatal exposures in the first trimester were higher among nonlive pregnancies than among live-birth pregnancies, with the largest difference observed for warfarin (nonlive 370 vs live birth 78), followed by valproate (258 vs 86) and topiramate (1728 vs 674). Prenatal exposures to medications with potential teratogenic risk were most prevalent for low-dose fluconazole (6495), metoprolol (1325), and atenolol (448). The largest first-trimester exposure differences between nonlive and live-birth pregnancies were observed for lithium (242 vs 89), gabapentin (1639 vs 653), and duloxetine (1914 vs 860). Steady increases in hydralazine and gabapentin exposures were observed during the study years, whereas atenolol exposure decreased (561 to 280).
Several medications with teratogenic risk for which there are potentially safer alternatives continue to be used during pregnancy. The fluctuating rates of prenatal exposure observed for select teratogenic medications suggest that regular reevaluation of risk mitigation strategies is needed. Future research focusing on understanding the clinical context of medication use is necessary to develop effective strategies for reducing exposures to medications with teratogenic risk during pregnancy.

UNASSIGNED: Priapism induces regulation of Transforming Growth Factor-β1 (TGF-β1) expression and collagen-type-1 deposition. This will replace the normal corpora cavernosa with fibrotic tissue which eventually resulted in erectile dysfunction. It is also known that the fibrosis process of corpora cavernosa is related to Renin-Angiotensin II System (RAS). Angiotensin II receptor blockers (ARB), especially losartan, inhibit the inflammation process and fibrotic tissue formation. This study evaluated the effect of losartan in reducing fibrosis in priapism by evaluating TGF-β1 and collagen-type-1 in cavernous tissue and determined the effect of losartan in preventing fibrosis in priapism model of Wistar rats assessed by the metavir score.
UNASSIGNED: A total of eighteen male Wistar rats mean were divided into five groups. For the priapism models, we applied negative pressure on the penis to make an artificial erection to mimic the priapism process. The control groups were observed and the treatment groups were orally given losartan 15 mg/kg/day. Corpora cavernosa was harvested for TGF-β1 and collagen-type-1 measurement using an enzyme-linked immunosorbent assay (ELISA). The fibrotic tissue of each rat was then collected and assessed histopathologically with the metavir scoring system.
UNASSIGNED: Penile TGF-β1 concentration in the losartan-treated group was not significantly different on day 10 and day 28 of observation (p10=0,30; p28=0,17). Meanwhile, collagen-type-1 concentration was significantly lower compared to control group (p10=0,002; p28=0,01). There was a significant difference in metavir scores in rats that received losartan and those who did not (p<0,05).
UNASSIGNED: Losartan could suppress the fibrosis process in the priapism model. It could decrease the collagen type 1 deposition during corpora cavernosa tissue regeneration. Based on the metavir score, the group receiving losartan therapy was better than the control group.

UNASSIGNED: Angiotensin receptor-neprilysin inhibitor (ARNI) is an established treatment for heart failure. However, whether ARNI has renoprotective effects beyond renin-angiotensin system inhibitors alone in cardiorenal syndrome (CRS) has not been fully elucidated. Here, we examined the effects of ARNI on the heart and kidneys of CRS model mice with overt albuminuria and identified the mechanisms underlying ARNI-induced kidney protection.
UNASSIGNED: C57BL6 mice were subjected to chronic angiotensin II infusion, nephrectomy, and salt loading (ANS); they developed CRS phenotypes and were divided into the vehicle treatment (ANS-vehicle), sacubitril/valsartan treatment (ANS-ARNI), and two different doses of valsartan treatment (ANS-VAL M, ANS-VAL H) groups. Four weeks after treatment, the hearts and kidneys of each group were evaluated. The ANS-vehicle group showed cardiac fibrosis, cardiac dysfunction, overt albuminuria, and kidney fibrosis. The ANS-ARNI group showed a reduction in cardiac fibrosis and cardiac dysfunction compared with the valsartan treatment groups. However, regarding the renoprotective effects characterized by albuminuria and fibrosis, ARNI was less effective than valsartan. Kidney transcriptomic analysis showed that the ANS-ARNI group exhibited a significant enhancement in the phosphoinositide 3-kinase (PI3K)-AKT signalling pathway compared with the ANS-VAL M group. Adding PI3K inhibitor treatment to ARNI ameliorated kidney injury to levels comparable with those of ANS-VAL M while preserving the superior cardioprotective effect of ARNI.
UNASSIGNED: PI3K pathway activation has been identified as a key mechanism affecting remnant kidney injury under ARNI treatment in CRS pathology, and blockading the PI3K pathway with simultaneous ARNI treatment is a potential therapeutic strategy for treating CRS with overt albuminuria.