Angiotensin II receptor blockers (ARBs), also known as angiotensin II receptor antagonists, AT1 receptor antagonists or sartans, are a group of pharmaceuticals that modulate the renin angiotensin system. 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 the similar-attributed ACE inhibitors are both indicated as the first-line antihypertensives in patients developing hypertension along the left-sided heart failure. However, ARBs appear to produce less adverse effects compared to ACEs.
It was reported in a retrospective series that angiotensin receptor blockers might be associated with reduced peritumoral edema. The ASTER study is a randomised, 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 GBM.
Patients with a histologically confirmed GBM 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 outcomes 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 events 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 GBM patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov 1).
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.