Medical Bulletin 13/October/2023

Overview

Here are the top medical news of the day:

Treatment-resistant epilepsy: New drug shows promise

Many individuals with focal epilepsy continue to experience seizures even with the use of currently available antiseizure medications (ASMs). However, a new treatment approach has shown great potential in addressing this issue. XEN1101, a novel small-molecule selective Kv7.2/Kv7.3 potassium channel opener, was evaluated in a phase 2b clinical trial for its efficacy and safety in the treatment of focal-onset seizures (FOSs).

The study, which took place over an 8-week treatment period, investigated XEN1101 from January 30, 2019, to September 2, 2021. The trial was conducted as a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging adjunctive study, involving adults who were experiencing four or more monthly FOSs despite receiving stable treatment with 1-3 ASMs. The research was conducted at 97 sites in North America and Europe.

Patients were randomly assigned to one of four groups: XEN1101 at doses of 25 mg, 20 mg, or 10 mg, or a placebo, which they took with food once daily for 8 weeks. Notably, XEN1101 demonstrated a robust dose-response relationship in reducing seizures. The median percent reduction from baseline in monthly focal-onset seizures (FOS) frequency was 52.8% for 25 mg, 46.4% for 20 mg, and 33.2% for 10 mg, compared to 18.2% for the placebo group. These results were statistically significant.

Importantly, XEN1101 was found to be generally well-tolerated, with Treatment-emergent adverse events comparable to those of commonly prescribed ASMs, and no Treatment-emergent adverse events leading to death were reported during the trial.

Ref:French JA, Porter RJ, Perucca E, et al. Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults With Focal Epilepsy: A Phase 2b Randomized Clinical Trial. JAMA Neurol. Published online October 09, 2023. doi:10.1001/jamaneurol.2023.3542

Large Infarct Stroke: Endovascular Thrombectomy Shows Promise

Endovascular thrombectomy significantly improves functional outcomes and reduces mortality in acute ischemic stroke patients with large infarcts, even when using non-contrast CT for patient selection, a recent study published in The Lancet has shown.

In this trial, patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation, along with a large established infarct indicated by a specific score (ASPECTS 3-5), were enrolled. The study, conducted in 40 hospitals in Europe and one site in Canada, used a central web-based system to randomly assign patients to receive either endovascular thrombectomy in addition to medical treatment or medical treatment alone, within 12 hours from the onset of the stroke.

Between July 17, 2018, and February 21, 2023, a total of 253 patients were randomly assigned, with 125 receiving endovascular thrombectomy and 128 receiving medical treatment alone. Astonishingly, the trial was halted early due to the treatment's remarkable efficacy, as indicated by the results of the first pre-planned interim analysis.

At the 90-day mark, the endovascular thrombectomy group showed a significant improvement in the distribution of scores on the modified Rankin Scale, pointing towards better outcomes. Moreover, the thrombectomy group had a lower mortality rate. Symptomatic intracranial hemorrhage, a critical safety concern, occurred in a limited number of cases, with 6% of patients in the thrombectomy group and 5% in the medical treatment group experiencing this complication.

Ref:Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial, Prof Martin Bendszus, et al.October 11, 2023, DOI:https://doi.org/10.1016/S0140-6736(23)02032-9

Amlodipine : Study Dispels Concerns About the Drug Causing Heart Failure

A new paper published by Oxford University Press, finds that a widely prescribed drug for treating hypertension, amlodipine, is not dangerous for patients, despite recent concerns from researchers and clinicians that taking amlodipine may have risks. Amlodipine inhibits a type of calcium channel that is found on blood vessels. When the calcium channel opens, calcium enters the muscle and causes it to constrict, increasing blood pressure. Amlodipine prevents calcium from coming in, leading to vessel relaxation and a decrease in blood pressure.

Recently some researchers have questioned the benefit of amlodipine for treating hypertension. Studies suggested that amlodipine may activate a different type of calcium channel, resulting in changes to blood vessels and an increase in heart failure in patients. Removing amlodipine as a prescribed anti-hypertensive medication carries significant health implications, since hypertension is such a common health condition.

A new study by research teams from National Institutes of Health and Glasgow University finds that taking amlodipine is unlikely to result in an increase in heart failure in patients. The researchers found that amlodipine appears to have unique chemical properties that caused the drug to mimic the calcium channel activation, without in fact opening the channels as clinicians worried.

When the study’s authors controlled for these chemical properties, they found that amlodipine did not activate calcium channels. A meta-analysis combining clinical trials and a prospective real-world analysis both showed that amlodipine was not associated with increased heart failure or other cardiovascular problems.

Ref:A reappraisal of the effects of L-type Ca2+ channel blockers on store-operated Ca2+ entry and heart failure,JOURNAL: Function DOI10.1093/function/zqad047