====== Angiotensin II receptor blocker ====== [[Angiotensin]] II [[receptor]] [[blocker]]s (ARBs), also known as [[angiotensin II receptor]] [[antagonist]]s, AT1 receptor antagonists or sartans, are a group of pharmaceuticals that modulate the [[renin angiotensin system]]. ===== Indications ===== Their main uses are in the treatment of [[arterial hypertension]], [[diabetic nephropathy]] and congestive heart failure. They block the activation of AT1 receptors, preventing the binding of angiotensin II. ARBs and similar-attributed ACE inhibitors are both indicated as the first-line antihypertensives in patients developing [[hypertension]] along with left-sided heart failure. However, ARBs appear to produce fewer adverse effects compared to ACEs. ---- Analysis suggests that several types of [[statin]]s, [[calcium channel blocker]]s, and [[angiotensin II receptor blocker]]s are candidate drugs for the preventive [[unruptured intracranial aneurysm treatment]] ((Shimizu K, Imamura H, Tani S, Adachi H, Sakai C, Ishii A, Kataoka H, Miyamoto S, Aoki T, Sakai N. Candidate drugs for preventive treatment of unruptured intracranial aneurysms: A cross-sectional study. PLoS One. 2021 Feb 12;16(2):e0246865. doi: 10.1371/journal.pone.0246865. PMID: 33577580.)). ---- It was reported in a retrospective series that [[angiotensin receptor blocker]]s might be associated with reduced [[peritumoral edema]]. The ASTER study is a randomized, placebo-controlled trial to assess whether or not the addition of [[Losartan]] to standard of care (SOC) can reduce [[steroid]] requirement during [[radiotherapy]] (RT) in patients with newly diagnosed [[Glioblastoma]]. Patients with a histologically confirmed Glioblastoma after [[biopsy]] or partial surgical [[resection]] were randomised between Losartan or placebo in addition to SOC with RT and [[temozolomide]] (TMZ). The primary objective was to investigate the steroid dosage required to control [[brain edema]] on the last day of RT in each arm. The secondary [[outcome]]s were steroids dosage 1 month after the end of RT, assessment of cerebral oedema on [[magnetic resonance imaging]], tolerance and survival. Seventy-five patients were randomly assigned to receive Losartan (37 patients) or [[placebo]] (38 patients). No difference in the steroid dosage required to control [[brain edema]] on the last day of RT, or one month after completion of RT, was seen between both arms. The [[incidence]] of [[adverse event]]s was similar in both arms. Median [[overall survival]] was similar in both arms. Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed Glioblastoma patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov ((Ursu R, Thomas L, Psimaras D, Chinot O, Le Rhun E, Ricard D, Charissoux M, Cuzzubbo S, Sejalon F, Quillien V, Hoang-Xuan K, Ducray F, Portal JJ, Tibi A, Mandonnet E, Levy-Piedbois C, Vicaut E, Carpentier AF. Angiotensin II receptor blockers, steroids and radiotherapy in glioblastoma-a randomised multicentre trial (ASTER trial). An ANOCEF study. Eur J Cancer. 2019 Feb 1;109:129-136. doi: 10.1016/j.ejca.2018.12.025. [Epub ahead of print] PubMed PMID: 30716716. )). ---- A study aimed to investigate whether pre-[[stroke]] treatment with fimasartan, an angiotensin II receptor blocker, has anti-inflammatory effects on [[ICH]] by inhibiting the activation of the NLRP3 inflammasome. Sprague-Dawley rats were divided into five groups: sham, vehicle, low-dose (0.5 mg/kg) and regular-doses (1.0 and 3.0 mg/kg) fimasartan. These rats were treated for 30 days before the induction of collagenase-induced ICH and continuously 3 days after surgery. The mean blood pressure (BP) in the low-dose fimasartan group was not significantly different from that of control, and BP in the regular-dose groups was decreased in a dose-dependent manner. Pretreatment with low-dose fimasartan attenuated ICH-induced edema and improved neurological functions. Activation of the NLRP3/ASC/caspase-1 and the NF-κB pathways after ICH was markedly reduced by low-dose fimasartan. The double immunofluorescence staining of brain cells showed a significant decrease in the co-localization of NLRP3 with Iba1 (microglia marker) positive cells by fimasartan treatment. Cultured microglia cells stimulated by hemolysate demonstrated significant activation of the inflammasome, which was reduced by fimasartan. Pretreatment with a low-dose fimasartan alleviated brain damage after acute ICH by inhibiting the NLRP3 inflammasome without lowering MBP. The study suggests pre-stroke administration of fimasartan could potentially attenuate ICH-induced secondary brain injury by targeting the [[inflammasome]] ((Yang X, Sun J, Kim TJ, Kim YJ, Ko SB, Kim CK, Jia X, Yoon BW. Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage. Exp Neurol. 2018 Dec;310:22-32. doi: 10.1016/j.expneurol.2018.08.013. Epub 2018 Aug 29. PubMed PMID: 30171865; PubMed Central PMCID: PMC6203658. )). ===== Side effects and risks ===== Side effects of ARBs include: headache fainting dizziness fatigue respiratory symptoms vomiting and diarrhea back pain leg swelling high potassium levels In rare cases, some people taking an ARB may have: allergic reactions liver failure kidney failure angioedema, or tissue swelling lower white blood cell (WBC) counts irregular heartbeat caused by high blood potassium levels Some drugs may not work well with ARBs. Taking ARBs and ACE inhibitors together should be avoided as this may increase the risk of low blood pressure, kidney damage, and high potassium levels. Pain relievers such as ibuprofen (Advil) and naproxen (Aleve, Naprosyn) may also interact with ARBs to affect your potassium levels. ---- In an [[observational]] cohort study of US adults at high [[cardiovascular disease]] risk, there was no difference in the rate of amnestic mild [[cognitive impairment]] (MCI) or probable [[dementia]] (PD). among new users of an [[angiotensin II receptor blocker]] (ARB) compared with [[ACE inhibitor]] ([[ACE]]I), although 95% of [[cognitive impairment]]s were wide ((Cohen JB, Marcum ZA, Zhang C, Derington CG, Greene TH, Ghazi L, Herrick JS, King JB, Cheung AK, Bryan N, Supiano MA, Sonnen JA, Weintraub WS, Scharfstein D, Williamson J, Pajewski NM, Bress AP; Systolic Blood Pressure Intervention Trial (SPRINT) Research Group. Risk of Mild Cognitive Impairment or Probable Dementia in New Users of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors: A Secondary Analysis of Data From the Systolic Blood Pressure Intervention Trial (SPRINT). JAMA Netw Open. 2022 Jul 1;5(7):e2220680. doi: 10.1001/jamanetworkopen.2022.20680. PMID: 35834254.)) ===== References =====