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Netherlands: A recent real-world, long-term study from the BioDay Registry has highlighted a significant incidence of Dupilumab-Associated Ocular Surface Disease (DAOSD) in pediatric patients receiving dupilumab for atopic dermatitis (AD). The findings, published in Clinical & Experimental Allergy, emphasize the need for heightened vigilance in monitoring ocular symptoms, particularly in younger children who may have difficulty reporting their symptoms, potentially leading to delayed diagnosis.

Among patients with uncontrolled hypertension, the investigational drug lorundrostat brought a significant reduction in blood pressure at 12 weeks compared with placebo, according to a study presented at the American College of Cardiology’s Annual Scientific Session (ACC.25).

The Phase 2b trial is only the second study to test lorundrostat’s blood pressure lowering ability in patients. Twenty-four-hour average ambulatory blood pressure, the trial’s primary endpoint, dropped by 7.9 mm Hg and 6.5 mm Hg more than placebo in the two study groups that received the drug (with one group receiving 50 mg of the drug daily and the other group receiving 50 mg to 100 mg). At four weeks, 42% of those taking lorundrostat had their blood pressure under control, compared with 19% in the placebo group.

“Lorundrostat effectively lowered blood pressure with an acceptable side effect profile,” said Luke Laffin, MD, a cardiologist at Cleveland Clinic and the study’s first author. “More studies are needed; however, this drug could be another tool in our armamentarium to reduce blood pressure and, ultimately, reduce the risk from uncontrolled hypertension in terms of outcomes like strokes, heart attacks and heart failure.”

High blood pressure, or hypertension, is a key modifiable risk factor for heart disease. Studies suggest that blood pressure remains uncontrolled in over two-thirds of people with hypertension in the United States, either because they are not taking blood pressure-lowering drugs or available drugs are not working for them.

Lorundrostat is in a new class of blood pressure medications called aldosterone synthase inhibitors (ASIs). Several ASIs are currently in development and are designed to work by disrupting the production of aldosterone, a hormone that can contribute to hypertension. Many existing blood pressure-lowering drugs work by blocking aldosterone from binding to its receptor but do not interfere with the hormone’s production.

The trial, called ADVANCE-HTN, enrolled 285 patients at 103 sites in the U.S. Participants had elevated blood pressure despite taking two to five blood pressure-lowering medications before joining the study. The average age of participants was 60 years and 40% were women. Over half of the study’s participants (53%) were Black.

“Black Americans have a disproportionate burden of treatment-resistant hypertension, yet they have been underrepresented in anti-hypertensive drug trials,” Laffin said. “It was very important to us to study this drug in this population that really needs new options for controlling blood pressure.”

The researchers said the results did not show any differences in the drug’s effectiveness among different racial groups.

The study began with a three-week run-in period during which all participants received a standardized set of blood pressure-lowering medications. Those who still had uncontrolled blood pressure at that point were then randomly divided into three groups and assigned to take either a placebo, 50 mg lorundrostat daily or 50 mg lorundrostat with the potential to increase to 100 mg daily if their blood pressure remained uncontrolled after four weeks. Among participants in the third group, 20% met the criteria to increase their dose to 100 mg and the rest continued taking 50 mg per day.

At four and 12 weeks, participants were asked to wear a device that continuously monitors blood pressure for 24 hours while going about their daily activities. On average, the 24-hour mean ambulatory blood pressure dropped in all three groups. At 12 weeks, this measurement fell by 15.4 mm Hg among those receiving 50 mg lorundrostat, 13.9 mm Hg among those receiving 50-100 mg lorundrostat and 7.4 mm Hg among those receiving a placebo. The change in blood pressure compared with placebo was significant in both lorundrostat groups, meeting the trial’s primary endpoint.

The results showed consistent patterns across secondary endpoints including change in blood pressure as measured in a medical office and in all types of blood pressure measurements at both four and 12 weeks.

The side effects experienced by patients taking lorundrostat were consistent with other drugs that work through a similar mechanism, researchers said. Some participants saw an increase in potassium in the blood and some experienced a decrease in glomerular filtration rate, a measure of kidney functioning.

“It was overall a well-tolerated drug,” Laffin said.

Another pivotal lorundrostat trial is currently underway with results expected later this year.

Reference:

Lorundrostat lowers blood pressure compared with placebo at 12 weeks, American College of Cardiology, Meeting: American College of Cardiology’s Annual Scientific Session

Patients with severe aortic stenosis at low surgical risk who underwent supra-annular, self-expanding Evolut transcatheter aortic valve replacement (TAVR) had similar rates of death or disabling stroke at five years compared with those whose valves were replaced through standard open heart surgery, based on new follow-up data from the Evolut Low Risk trial presented at the American College of Cardiology’s Annual Scientific Session (ACC.25).

Evolut Low Risk is a large, prospective trial that initially enrolled 1,478 patients at 86 centers in the United States, Canada, Europe, Japan, Australia and New Zealand to compare the safety and efficacy of Evolut TAVR to surgery. Patients were randomized to TAVR (n=737) or surgical aortic valve replacement (SAVR) (n=741). Both groups were well-matched in terms of baseline characteristics such as hypertension, coronary disease and lung disease; patients were 74 years old, on average, and one-third were women.

Follow-up data was available for 91% of TAVR patients and 87.4% of SAVR patients for the five-year analysis. Of these patients, the primary endpoint of death or disabling stroke occurred in 15.5% of those receiving Evolut TAVR and 16.4% of those undergoing SAVR.

“The outcomes of all-cause mortality and disabling stroke remain similar between TAVR and surgery, though numerically TAVR remains better,” said Michael J. Reardon, MD, professor and Allison Family Distinguished Chair of Cardiovascular Research at Houston Methodist Hospital and the study’s senior author. “TAVR has also shown similar improvements in terms of symptom and functional class and there’s no difference in the rate of reinterventions, so the supra-annular, self-expanding Evolut TAVR looks really good at five years in this group of patients.”

In addition to the combined rates of death and disabling stroke being similar between the two groups, the rates of disabling stroke were also comparable at five years (3.6% for TAVR and 4% for surgery) with no difference between year four and year five. All-cause mortality widened slightly during this period, though deaths remained similar between the two groups (13.5% for TAVR and 14.9% for surgery), Reardon said. Cardiovascular-related deaths were similar from two years to five years post-intervention and there was also no difference in reintervention rates between the groups at five years.

When examining all-cause mortality between the groups, Reardon said the deaths were primarily driven by non-cardiovascular events, including cancer-related deaths (seven in the TAVR group and one in SAVR), sepsis (three in TAVR) and COVID-19 (three in TAVR and two in SAVR).

“The difference in cardiovascular deaths is maintained over the five years of the trial, which is reassuring as these deaths are related to how well the aortic valve works,” Reardon said. “In looking at cardiovascular deaths alone, they occurred in 7.2% of people with TAVR at 9.3% at five years—the curves looked similar, the delta was 1.1% at two years and now at five years is 2.1%, which gives us strong confidence that the performance of the valve compared with surgery remains very good.”

Quality of life, measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), which allows patients to report their functional ability and wellness, stayed high through five years for both Evolut TAVR and surgery. Based on the scores, researchers report that approximately 70% of patients in both groups are alive and well at five years.

As shown previously, patients receiving TAVR had significantly fewer cases of atrial fibrillation, superior hemodynamics (blood flow through the heart), more pacemakers and more paravalvular regurgitation (leakage around the valve), which decreased over time.

TAVR, which involves threading a replacement valve through a catheter in the groin or chest, has emerged as the leading procedure for treating symptomatic severe aortic stenosis in the U.S., irrespective of the patient’s surgical risk. With TAVR, most patients are out of the hospital within a few days and back to their normal activities within a week versus more extended recovery time with surgery. Patients randomized to TAVR in this study received the Medtronic Evolut R, PRO or CoreValve bioprosthesis as new generation valves became available during the study.

Aortic stenosis-when the valve in the heart’s main artery doesn’t open fully-forces the heart to work harder to pump blood and can be life-threatening. TAVR is now FDA approved for use in high, intermediate and low surgical risk patients with severe aortic stenosis. Low risk was defined as a predicted 30-day mortality of 3% or less for 30 days post-surgery and was based on a combination of clinical judgment from the local heart team and an independent screening committee.

Reardon and team plan to follow patients for 10 years, which should yield important long-term data about TAVR’s durability compared with surgically implanted valves, as well as the life of the valves themselves.  

Reference:

Five-year outcomes similar for low-risk patients receiving transcatheter, surgical aortic valve replacement, American College of Cardiology, Meeting:American College of Cardiology’s Annual Scientific Session.

Researchers have found in a new study that individuals who live alone and experience depression or anxiety have a higher risk of suicide. The findings emphasize the need for targeted mental health interventions and suicide-prevention strategies to support vulnerable individuals. Living alone and mental health disorders, including depression and anxiety, are associated with high suicide risk, but their combined impact remains underexplored. A study was done to examine the association of living arrangements and depression or anxiety with suicide risk. This population-based cohort study used data from the Korean National Health Insurance Service database from January 1, 2009, to December 31, 2021, that included adults aged 20 years or older who participated in the General Health Screening Program in Korea in 2009. Individuals with incomplete data and those who died by suicide within the first year were excluded to minimize the possibility of reverse causation. Data were analyzed from December 28, 2023, to December 27, 2024. Living arrangements, categorized as living alone (≥5 years) or living with others, and depression and anxiety, determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. The primary outcome was death by suicide, identified through national death records. Multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (AHRs) and 95% CIs for suicide risk. Results The study included 3 764 279 adults (mean [SD] age, 47.2 [14.0] years; 55.8% male). Of these individuals, 112 460 (3.0%) had depression, 232 305 (6.2%) had anxiety, and 319 993 (8.5%) lived alone. Compared with individuals who had neither depression nor anxiety nor lived alone, individuals living alone with both depression and anxiety exhibited a 558% increased risk of suicide (AHR, 6.58 [95% CI, 4.86-8.92]). Living alone with depression was associated with a 290% increased risk (AHR, 3.91 [95% CI, 2.96-5.16]), and living alone with anxiety was associated with a 90% increased risk (AHR, 1.90 [95% CI, 1.48-2.43]). The AHRs were higher for the association between living alone and suicide among middle-aged individuals (aged 40 to 64 years) and men compared with other demographic groups. In this cohort study of 3 764 279 individuals, living alone with depression or anxiety was associated with an increased risk of suicide, particularly among middle-aged individuals and men. These findings underscore the importance of preventing mental illness, such as depression and anxiety, while addressing living arrangements as a critical factor in suicide risk assessments for individuals with these conditions.