Zerlasiran shows beneficial outcomes for cardiovascular disease reveals phase 2 study

Researchers have announced a promising 36-week topline data from its phase 2 ALPACAR-360 study which evaluating the efficacy of zerlasiran in patients at high risk of atherosclerotic cardiovascular disease (ASCVD). Zerlasiran, Silence’s pioneering siRNA (short interfering RNA) therapy targets the reduction of lipoprotein(a) or Lp(a) as a critical genetic risk factor for cardiovascular diseases that affect a significant portion of the global population.

This comprehensive study included a total of 178 subjects with increased levels of lipoprotein(a), or Lp(a), a genetic factor known to contribute to cardiovascular disease in up to 20% of the global population. This double-blind, placebo-controlled phase 2 trial administered zerlasiran at doses of 300 mg every 16 or 24 weeks and 450 mg every 24 weeks to participants, who had a median baseline Lp(a) of approximately 215 nmol/L. Also, the study reported a median reduction in Lp(a) levels of 90% or greater at the 36-week mark when compared to the placebo group, with no new safety concerns emerging.

The ongoing 60-week study will further assess secondary endpoints of changes in Lp(a) levels from baseline to 48 and 60 weeks, along with potential impacts on other lipid profiles. These findings bolster the potential of zerlasiran as a transformative treatment for patients with high Lp(a) by addressing a significant unmet need in cardiovascular disease management.

The Head of Research and Development at Silence, Dr. Steven Romano, expressed enthusiasm about the phase 2 results marking their consistency with phase 1 outcomes and the competitive profile of zerlasiran for treating high Lp(a) levels. The company anticipates the release of further data from the ALPACAR-360 study in the coming months with the hopes to advance zerlasiran towards regulatory approval and commercial availability.

Silence Therapeutics stands at the forefront of RNA interference (RNAi) technolog and is constantly developing a new class of precision medicines aimed to silence genes implicated in various diseases. Its proprietary mRNAi GOLD™ platform facilitates the creation of siRNAs targeting disease-associated genes in the liver that offer a broad therapeutic potential. Along with zerlasiran, the pipeline includes divesiran for hematological conditions and ongoing collaborations with industry leaders like AstraZeneca and Hansoh Pharma. While the future of zerlasiran looks promising, Silence Therapeutics cautions the investors and stakeholders about forward-looking statements by illuminating the inherent risks and uncertainties in drug development and approval processes.

Source:

(N.d.-a). Silence-therapeutics.com. Retrieved March 22, 2024, from https://silence-therapeutics.com/investors/press-releases/press-releases-details/2024/Silence-Therapeutics-Announces-Positive-Topline-36-Week-Data-from-Ongoing-Phase-2-Study-of-Zerlasiran-in-Patients-with-High-Lipoproteina/default.aspx

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KIMS Bhubaneswar doctor saves woman mid-air

Bhubaneswar: In a remarkable display of quick thinking and medical expertise, Dr Ashok Kumar Badamali, senior consultant in Cardiac Anesthesia at Kalinga Institute of Medical Sciences (KIMS) Bhubaneswar, saved the life of a fellow passenger aboard Air India Express flight I5 764 enroute from New Delhi to Pune. 

The incident, which unfolded in the early hours of the morning, began when the cabin crew, led by Mr. Saurav, made an urgent announcement requesting the assistance of any onboard paramedics or nursing personnel due to a medical emergency.

A middle-aged woman was found unresponsive in her seat, prompting immediate action. Dr Badamali, who was traveling to Pune for research activities, promptly responded to the call for help. The patient was moved to the floor of the aircraft to facilitate resuscitation efforts. Upon examination, Dr. Badamali found the patient to be unresponsive, and exhibiting agonal breathing, with an extremely fast carotid pulse. Utilizing his expertise in cardiac emergencies, he performed a carotid massage that proved to be life-saving. 

Also Read:Doctors at KIMS Health perform carotid revascularization procedure to remove 10-cm-long occluded blockage

Under Dr Badamali’s careful management, the patient was placed in the recovery position and remained stable until the flight successfully landed at Pune International Airport. This act of quick thinking and medical intervention highlights the critical importance of having medical professionals readily available and able to respond in flight emergencies.

Reflecting on the incident, Dr Badamali noted a few constraints in the current emergency response protocols aboard flights. He said that he will draft and send a Standard Operating Procedure (SOP) to the Aviation Ministry to enhance the management of such medical emergencies in the future, aiming to improve the safety and well-being of passengers.

The pilot of the flight, Mr. Rahul, along with crew members Mr. Saurav and Miss Puja, expressed their profound gratitude to Dr Badamali for his timely and decisive action. They assured him that an incident report would be submitted to the concerned authorities to document the event and the effective response.

Also Read:KIMS Hospital doctors successfully remove massive chest tumour from 25-year-old woman

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Total chemical matricectomy with phenol effective treatment of symptomatic nail dystrophy, finds study

Nail dystrophies, whether congenital, traumatic, or acquired, can significantly impact the quality of life of affected individuals, particularly elderly patients. While periodic conservative treatments are common, they may not always provide satisfactory outcomes. In such cases, surgical intervention, such as total matricectomy with 88% phenol solution, emerges as an alternative method, especially for symptomatic patients.

In a recent study, a series of 48 surgeries were performed on 37 patients to evaluate the effectiveness of total matricectomy with 88% phenol solution for treating nail dystrophies. This study was published in the journal of Dermatologic Surgery by Matter A. and colleagues. Parameters such as pain evaluation, interference with shoes and gait, recurrences, and patients’ satisfaction with the procedure were assessed.

The key findings of the study were:

  • Before surgery, all patients reported some degree of pain or impairment in wearing shoes.

  • Following the procedure, remarkable cosmetic results were observed, with 95.11% of patients experiencing a dramatic improvement in discomfort.

  • No severe complications occurred during the 12-month follow-up period, indicating low rates of postoperative morbidity.

  • It’s important to note that this study was conducted at a single center and involved a limited number of patients, which may affect the generalizability of the findings.

Total matricectomy with 88% phenol solution emerges as an effective surgical method for treating symptomatic nail dystrophies. The procedure demonstrates high success rates, low rates of postoperative morbidity, and high patient satisfaction with cosmetic outcomes. Importantly, it is deemed safe even for patients with associated comorbidities.

Reference:

Matter, A., Di Chiacchio, N. G., Iorizzo, M., & Di Chiacchio, N. (2024). Total chemical matricectomy with 88% phenol: A prospective case series of 37 patients. Dermatologic Surgery, 10.1097/DSS.0000000000004134. https://doi.org/10.1097/dss.0000000000004134

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New Potential treatment found for patients suffering from Myasthenia Gravis: Study

For the thousands of people globally affected by the disease myasthenia gravis (MG), everyday activities become a struggle, and in severe cases, the disease can be life-threatening.

Until now, there has been no muscle-specific and effective treatment against this rare autoimmune disease that leads to severe weakening of the muscles and fatigue. But now, a team of researchers from Aarhus University reveals a breakthrough in the treatment of MG that could give hope to many patients worldwide.

“The patients simply became stronger because the new treatment improves the communication between motor nerves and muscle fibers,” says Thomas Holm Pedersen, an associate professor at the Department of Biomedicine at Aarhus University, CEO of NMD Pharma, and the lead author of the study that has just been published in the journal Science Translational Medicine.

Focusing on the link between nerve cells and muscles

MG is a disease where the immune system attacks the connection between nerves and muscle cells. It can affect breathing and be life-threatening, and it was precisely these symptoms that the researchers aimed to combat by strengthening the function of the contact point between nerves and muscle cells.

During his PhD project at Aarhus University, Thomas Holm Pedersen discovered that the so-called CIC-1 chloride channels at the neuromuscular junction are crucial for muscle activation.

“This led to the idea of using the CI channels as a new treatment point for diseases where the neuromuscular connection is compromised, including myasthenia gravis,” he explains.

And it proved to be a good idea. The researchers demonstrated that they could effectively strengthen the muscles’ ability to respond to nerve impulses by targeting a treatment at the specific channel. This, in theory, could increase muscle strength and reduce fatigue in patients.

“As there were no medications targeting the Cl channel, we first had to find the right molecule that we could test in patients, which requires considerable work and various tests before the regulatory authorities allow testing in humans. We tested it on patients who had to take a tablet daily for their muscle weakness and fatigue, and we could see that the treatment concept worked. The patients became stronger.

Treatment without side effects?

This represents a significant advance in the treatment of MG. Not only because it was successful in increasing muscle strength among patients, but also because the treatment, unlike existing methods, may well prove to be free from side effects.

“We won’t know for sure for a few years, after we’ve conducted more studies, but it looks really promising right now,” says Thomas Holm Pedersen.

The breakthrough could result in a significant improvement in the quality of life for patients struggling with MG, but it is also a big leap forward in the understanding and treatment of other neuromuscular diseases.

The research team is currently planning more follow-up clinical trials, including another study on MG and one on the hereditary disease spinal muscular atrophy, which leads to muscle wasting.

According to Thomas Holm Pedersen, we may be on the verge of a paradigm shift in the treatment of MG and other serious neuromuscular diseases.

“This study summarizes years of work here at Aarhus University and NMD Pharma. We have proven that the method works in patients, and now we continue with the clinical trials to bring the drug to the patients and to explore its broader application,” he says.

Reference:

Martin Skov et al. ,The ClC-1 chloride channel inhibitor NMD670 improves skeletal muscle function in rat models and patients with myasthenia gravis.Sci. Transl. Med.16,eadk9109(2024).DOI:10.1126/scitranslmed.adk9109.

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Adults with ideal CV health have lower risk of developing heart disease, stroke or kidney disease later in life: AHA

An analysis of health data for nearly 4 million young adults in Korea found that those who had ideal cardiovascular health had about a 65% lower risk of developing heart disease, stroke or kidney disease later in life compared to people with low heart health scores, according to preliminary research to be presented at the American Heart Association’s Epidemiology and Prevention, Lifestyle and Cardiometabolic Scientific Sessions 2024, March 18- 21, in Chicago. The meeting offers the latest science on population-based health and wellness and implications for lifestyle.

In a 2023 scientific statement and presidential advisory, the American Heart Association highlighted the link between heart disease and chronic kidney disease and the importance of improving cardiovascular health to prevent them.

“Cardiovascular disease is deadly, and kidney disease is quite common, even among younger adults,” said lead study author Hokyou Lee, M.D., Ph.D., an associate professor of preventive medicine at Yonsei University College of Medicine in Seoul, South Korea. “These two diseases should be prevented together because they often coexist or increase the likelihood of one another. However, the importance of ideal heart health behaviors and factors in young adults have often been overlooked due to their lower short-term risk of cardiovascular and kidney diseases.”

In this study, researchers reviewed data from the 2009-2010 Korean National Health Screening program to explore how cardiovascular health during young adulthood affects the risk of developing heart disease, stroke and kidney disease later in life. Participants’ heart health was assessed and scored using the three modifiable lifestyle behaviors and three health measures: being physically active, maintaining a healthy weight and quitting tobacco and blood pressure, cholesterol and blood sugar, from the American Heart Association’s Life’s Simple 7 metrics. (Note: In 2022, sleep health was added to the seven metrics in the Association’s new Life’s Essential 8 measures for optimal cardiovascular health.)

The analysis found:

  • Young adults with perfect heart health scores at enrollment had a 65% lower risk of developing cardiovascular or kidney disease during the 12-year follow-up compared to people with zero ideal cardiovascular health metrics. Note: In this study, a perfect heart health score was 6 out of 6 because a measure of diet was not available for participants.
  • The risk of developing cardiovascular or kidney disease decreased gradually with higher heart health scores.
  • People whose scores improved from low to high during follow-up also had a lower risk of developing cardiovascular or kidney disease compared to people who had consistently low heart health scores.

“Less than 1% of the young adults had ideal heart health scores at the beginning of the study, and, unfortunately, about half of those with perfect or near-perfect cardiovascular health eventually had lower heart health scores within a few years. However, fewer of the young adults with perfect or near-perfect cardiovascular health whose scores decreased experienced cardiovascular and kidney diseases than young adults who began with low heart health and remained that way,” Lee said. “Our study highlights the importance of achieving ideal cardiovascular health during young adulthood and maintaining or improving it throughout life. More effort is needed to raise awareness among young adults about implementing and maintaining heart-healthy lifestyle behaviors early in life to help them live longer, healthier lives.”

Study background information:

  • The study included 3,836,283 adults in South Korea who did not have a history of cardiovascular or kidney disease.
  • Participants self-identified as female (38.2%) and male (62.8%).
  • Participants were ages 20-39 years old, with a median age of 31 at the beginning of the study.

The study’s limitations included that it did not use the new Life’s Essential 8 health metrics to define cardiovascular health. In addition, dietary information about participants was not available, and the study included only people living in South Korea, which limits the generalizability of the study’s findings to other populations.

“The findings underscore the importance of early awareness of risk factors and intervention and the adoption of healthy lifestyle behaviors in young adulthood to prevent cardiovascular and kidney diseases later in life. Moreover, the research indicates that even individuals with initially low heart health scores who improved their cardiovascular health over time experienced a reduced risk of diseases compared to those with persistently low scores. This highlights the potential for positive health outcomes through lifestyle modifications,” said

Monica C. Serra, Ph.D., an associate professor and research investigator in the department of medicine in the Division of Geriatrics, Gerontology & Palliative Medicine and the Sam and Ann Barshop Institute for Longevity and Aging Studies at UT Health San Antonio in San Antonio, Texas. Serra is co-chair of the program committee of EPI│Lifestyle Scientific Sessions 2024.

“The use of the American Heart Association’s Life’s Simple 7 metrics, including modifiable behaviors such as physical activity, weight management and tobacco cessation, along with biometric measures like blood pressure, cholesterol and blood sugar, provides a comprehensive assessment of heart health. It is noteworthy that the study did not include dietary components, and the addition of sleep health in the Association’s new Life’s Essential 8 was acknowledged,” she said. “Overall, the research contributes valuable evidence to the importance of cardiovascular health maintenance in young adulthood for long-term disease prevention.”

Reference:

Adults younger than 40 with ideal heart health had lower heart disease, stroke, and kidney disease risk, American Heart Association, Meeting: AHA EPI|Lifestyle Scientific Sessions 2024.

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Survival rate of Metal–ceramic and monolithic zirconia implants 100% after 5 years, reveals study

The survival rate of Metal–ceramic and monolithic zirconia implants is 100% after 5 years, reveals a study published in the Journal of Clinical Medicine.

The current study aimed to present the clinical and radiological outcomes of monolithic zirconia superstructures compared to the metal–ceramic ones in the All-on-4 concept for the prosthetic rehabilitation of the maxillae. A total of 30 patients were subdivided into groups according to their superstructure type (metal–ceramic (n = 15) or monolithic zirconia (n = 15)). All implants were functionally loaded within 24 h after insertion with provisional acrylic superstructures. Prosthetic complications, marginal bone loss, plaque accumulation, probing pocket depth, bleeding on probing, and bite force were documented over 5 years. Marginal bone loss around the implants of the ceramic group remained well over the five years (1.21 ± 0.23 mm). However, marginal bone loss was significantly lower around the implants in the monolithic zirconia group (0.22 ± 0.14 mm) (p < 0.001). Bleeding on probing, plaque accumulation, and probing pocket depth values were correlated with marginal bone loss. Among all evaluated parameters, no differences could be detected in terms of the angulation of the implants. Detachment or chipping was observed in seven cases in the metal–ceramic superstructure group. In all cases, dentures were removed and repaired in the laboratory. In the monolithic zirconia group, chipping was detected after one year in two cases, after two years in four cases, and after five years in one case and could be managed by polishing in situ. Monolithic zirconia superstructures presented superior results regarding the parameters evaluated.

Reference:

Ayna M, Jepsen S. A Retrospective Evaluation of 5 Years of Clinical Results of Metal–Ceramic vs. Monolithic Zirconia Superstructures in Maxillary All-on-4TM Concept. Journal of Clinical Medicine. 2024; 13(2):557. https://doi.org/10.3390/jcm13020557

Keywords:

Survival rate, Metal–ceramic, monolithic zirconia implants,Ayna M, Jepsen S, Journal of Clinical Medicine, immediate loading; metal–ceramic; zirconia

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Cataract surgery and iStent Inject combo tied to significantly greater reduction of IOP in mild glaucoma patients: Study

Cataract surgery and iStent Inject combo tied to significantly greater reduction of IOP in mild glaucoma patients suggests a study published in the Ophthalmology Glaucoma.

A study was done to evaluate the efficacy and safety of combined cataract surgery with insertion of an ab interno trabecular micro bypass device (iStent Inject, Glaukos Corporation) compared to cataract surgery alone in patients with mild-to-moderate glaucoma. Eyes with visually-significant cataracts and mild-to-moderate glaucoma with preoperative intraocular pressure (IOP) of 12 – 30 mmHg on 0 to 3 ocular hypotensive medications. Participants’ eyes were randomised (2017-2020) 1:1 to combine cataract surgery with iStent Inject (treatment group, n=56) or cataract surgery alone (control group, n=48), and followed up for two years. The co-primary effectiveness endpoints were the number of ocular hypotensive medications and IOP at 24 months post-surgery. The secondary effectiveness endpoints were ocular comfort as measured by the Ocular Surface Disease Index (OSDI) and vision-related quality of life as measured by the Glaucoma Activity Limitation Questionnaire (GAL-9) at 24 months. Safety measures included postoperative visual acuity, any unplanned return to the operating theatre, adverse events, and complications. Results: Participants (67.3% male) were aged 53-85 years and treatment groups were similar in terms of mean medicated IOP (treatment group 17.7 mmHg ± 4.0; control group 17.1 mmHg ± 3.1), and number of ocular hypotensive medications (treatment group 1.69 ± 1.05; control group 1.80 ± 1.22) at baseline. At 24 months, the number of ocular hypotensive medications were 0.7 ± 0.9 in the treatment groups compared to 1.5 ± 1.9 in the control group, with an adjusted difference of 0.6 fewer medications per eye in the treatment group (95% CI 0.2 to 1.1, p=0.008). 57% of eyes in the treatment group were on no glaucoma medications compared to 36% in the control group. There was no significant difference in IOP between the two groups beyond the 4-weeks. There were no differences in patient-reported outcomes between the two groups. The visual outcomes and safety profiles were similar between the two groups. Combined cataract surgery with iStent Inject achieved a clinically- and statistically significantly greater reduction in ocular hypotensive medication usage at 24 months compared to cataract surgery alone, with no significant difference in IOP.

Reference:

Jennifer C. Fan Gaskin, Deus Bigirimana, George Yu Xiang Kong, Myra B. McGuinness, Alp Atik, Lei Liu, Anne MV. Brooks, Ghee Soon Ang. Prospective, Randomised Controlled Trial of Cataract Surgery versus combined Cataract Surgery with insertion of iStent Inject, Ophthalmology Glaucoma, 2024, ISSN 2589-4196, https://doi.org/10.1016/j.ogla.2024.02.004.

(https://www.sciencedirect.com/science/article/pii/S2589419624000310)

Keywords:

Cataract surgery, iStent, Inject, reduction of IOP, mild glaucoma patients, Ophthalmology Glaucoma, Glaucoma; glaucoma surgery; minimally- invasive glaucoma surgery; intraocular pressure, Jennifer C. Fan Gaskin, Deus Bigirimana, George Yu Xiang Kong, Myra B. McGuinness, Alp Atik, Lei Liu, Anne MV. Brooks, Ghee Soon Ang

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Study busts myth: Smoking doesn’t help to stay thin, increases belly fat

The worry of gaining weight is a common excuse for smokers not to quit. A new study published today in the scientific journal Addiction has found that both starting smoking and lifetime smoking may increase abdominal fat, especially visceral fat: the unhealthy fat deep inside the abdomen that is linked to a higher risk of heart disease, diabetes, stroke, and dementia.

Smokers tend to have lower body weights than non-smokers, but they also have more abdominal fat, and more abdominal visceral fat. Visceral fat is hard to see; you can have a flat stomach and still have unhealthy amounts of it, raising your risk of serious illness. This new study offers supportive evidence that smoking may cause that type of fat to increase.

Researchers at the NNF Center for Basic Metabolic Research, University of Copenhagen used a form of statistical analysis called Mendelian randomization (MR) to determine whether smoking causes an increase in abdominal fat. MR combines the results from different genetic studies to look for causal relationships between an exposure (in this case, smoking) and outcome (increased abdominal fat). This new study combined multiple genetic results from European ancestry studies of smoking exposures and measures of body fat distribution (e.g., waist-hip ratio and waist and hip circumferences).

First, the researchers used previous genetic studies to identify which genes are linked to smoking habits and body fat distribution. Second, they used this genetic information to determine whether people with genes associated with smoking tend to have different body fat distributions. Finally, they accounted for other influences, such as alcohol consumption or socioeconomic background, to ensure that any connections they found between smoking and body fat distribution were truly due to smoking itself and not other factors.

Lead author Dr. Germán D. Carrasquilla explains: “This study found that starting to smoke and smoking over a lifetime might cause an increase in belly fat, as seen by measurements of waist-to-hip ratio. In a further analysis, we also found that the type of fat that increases is more likely the visceral fat, rather than the fat just under the skin.”

“Previous studies have been prone to confounding, which happens when an independent variable affects the results. Because our study design uses genetic variations, it does a better job of reducing or controlling for those variables. The influence of smoking on belly fat seems to happen regardless of other factors such as socioeconomic status, alcohol use, ADHD, or how much of a risk-taker someone is.”

“From a public health point of view, these findings reinforce the importance of large-scale efforts to prevent and reduce smoking in the general population, as this may also help to reduce abdominal visceral fat and all the chronic diseases that are related to it. Reducing one major health risk in the population will, indirectly, reduce another major health risk.”

The researchers determined that excess abdominal fat in smokers was predominantly visceral fat by studying how DNA variants linked to smoking habits and belly fat relate to fat compartments in different parts of the body. The key finding is that these genetic factors are more strongly linked to increased visceral adipose tissue-the deep fat that wraps around the abdominal organs-than to subcutaneous fat that is stored under the skin.

The two underlying European ancestry studies were large in scale: the smoking study looked at 1.2 million people who started smoking and over 450,000 lifetime smokers, and the body fat distribution study included over 600,000 people.  

Reference:

Germán D. Carrasquilla, Mario García-Ureña, María J. Romero-Lado, Tuomas O. Kilpeläinen, Estimating causality between smoking and abdominal obesity by Mendelian randomization, Addiction, https://doi.org/10.1111/add.16454.

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Morphological characteristics of vestibular aqueduct associated with occurrence of Meniere disease: Study

Morphological characteristics of vestibular aqueduct associated with the occurrence of Meniere disease suggest a study published in the Largnygoscope.

A study was done to investigate the relationship between vestibular aqueduct (VA) morphology and Meniere’s disease (MD) using ultrahigh-resolution computed tomography (U-HRCT). Retrospective data were collected from 34 patients (40 ears) diagnosed with MD in our hospital who underwent temporal bone U-HRCT with the isotropic 0.05-mm resolution, magnetic resonance with gadolinium-enhanced, and pure-tone audiometry; 34 age- and sex-matched controls (68 ears) who underwent U-HRCT were also included. VA patency was qualitatively classified as locally not shown (grade 1), locally faintly shown (grade 2), or clearly shown throughout (grade 3). The width of the outer orifice and VA length and angle were quantitatively measured. Differences in VA morphology between the MD and control groups were analyzed. The correlations between VA morphology and the degrees of hearing loss and endolymphatic hydrops (EH) were also analyzed. Results: VA was classified as grades 1–3 in 11, 17, and 12 ears in the MD group and 5, 26, and 37 ears in the control group, respectively. The patency differed significantly between the groups (p < 0.01). The width of the outer orifice and length of VA were significantly smaller in the MD group than those in the control group (p < 0.05). Both VA patency and length were correlated with the degree of EH in the cochlea and the vestibule (p < 0.05). No difference was found between VA morphology and the degree of hearing loss (p > 0.05). The morphological characteristics of VA were found to be associated with the occurrence of MD and the degree of EH.

Reference:

Huang, Y., Tang, R., Xu, N., Ding, H., Pu, W., Xie, J., Yang, Z., Liu, Y., Gong, S., Wang, Z. and Zhao, P. (2024), Association Between Vestibular Aqueduct Morphology and Meniere’s Disease. The Laryngoscope. https://doi.org/10.1002/lary.31339

Keywords:

Morphological characteristics, vestibular aqueduct, occurrence, Meniere disease, Largnygoscope, Huang, Y., Tang, R., Xu, N., Ding, H., Pu, W., Xie, J., Yang, Z., Liu, Y., Gong, S., Wang, Z. and Zhao, P

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Lipoprotein (a) assay methods similarly predict MACE reduction with PCSK9 inhibitor Alirocumab: Study

USA: A recent comparison of changes in lipoprotein(a) mass and molar concentrations found that each essay method is similarly predictive of major adverse cardiovascular events (MACE) reductions with alirocumab (ALI).

The study stated, “With caveats of a modest number of MACE for analysis, moderately elevated Lp(a) levels, and intra-patient variability in serial values, three Lp(a) assay methods appeared comparably predictive of ALI MACE reduction, independent of reduction in LDL cholesterol,”

The findings were published online in the European Journal of Preventive Cardiology on March 19, 2024.

Baseline (BL) lipoprotein (a) concentrations are similarly related to cardiovascular (CV) risk when measured in either molar units or mass by immunoassay (IA). Because of Lp(a) isoform variation in mass, there may be differences between Lp(a) measurement methods in terms of relating change to risk reduction.

Against the above background, Michael Szarek, Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA, and colleagues determined whether the reduction in MACE by PCSK9 inhibitor alirocumab has a similar relationship to the reduction in Lp (a) concentration as measured by three different methods.

Lipoprotein (a) was measured by IA-molar (Roche), IA-mass (Siemens), and mass spectrometry (MS)-molar assays at baseline and month 4 (M4) in a subgroup of patients in the ODYSSEY OUTCOMES trial. The trial compared PCSK9 inhibitor ALI with placebo in patients with recent acute coronary syndrome.

Changes in Lp(a) from baseline to M4 were related to subsequent risk of MACE (nonfatal myocardial infarction, coronary heart disease death, unstable angina hospitalization, or fatal + nonfatal ischemic stroke) in the ALI group. Proportional hazard models were adjusted for baseline Lp(a), baseline LDL-C and its change from BL to M4, and other patient characteristics. Hazard ratios (HR) were calculated for the median change of each Lp(a) assay.

The study led to the following findings:

  • Among 5500 patients randomized to ALI with available data from all 3 Lp(a) assays, 443 experienced a subsequent MACE.
  • Changes in Lp(a) IA-mass and MS-molar concentration were significantly related to reduced MACE risk, while a change in IA-molar concentration was marginally significant; associations were more evident with coronary heart disease death + nonfatal MI.
  • MACE HRs for median change were similar across tests.

In conclusion, despite the relatively low number of MACE available for analysis, only moderately elevated lipoprotein levels, and intra-patient variability in serial value, the researchers showed that each of the 3 Lp(a) assay methods was similarly predictive of modest MACE reductions with alirocumab treatment.

“Greater clinical benefits might be observed, with the emergence of new potent Lp(a) lowering agents,” the researchers wrote.

Reference:

Szarek, M., Reijnders, E., Steg, P. G., Jukema, J. W., Schwertfeger, M., Bhatt, D. L., Bittner, V. A., Diaz, R., Fazio, S., Garon, G., Goodman, S. G., Harrington, R. A., White, H. D., Zeiher, A. M., Cobbaert, C., & Schwartz, G. G. Comparison of Change in Lipoprotein(a) Mass and Molar Concentrations by Alirocumab and Risk of Subsequent Cardiovascular Events in ODYSSEY OUTCOMES. European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwae110

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