Abstract
A groundbreaking clinical study recently published in Clinical Therapeutics has revealed significant milestones in the battle against hypercholesterolemia, a leading cause of heart disease. The study, undertaken within a Middle East population, provides valuable insights into the real-world application and effectiveness of inclisiran, a novel treatment for this life-threatening condition.
Introduction
Cardiovascular diseases (CVD) are the number one cause of death globally, with hypercholesterolemia as one of the major risk factors. The traditional cornerstone of treatment has been statins, but due to either side effects or inadequate response, alternative treatments are in demand. Inclisiran, a small interfering RNA (siRNA)-based therapy, has emerged as a revolutionary option, particularly for patients with uncontrolled LDL cholesterol levels despite standard care. This treatment strategy has the potential to alleviate the burden of CVD in populations across the Middle East and beyond.
The Study’s Impetus and Design
The study, led by Dr. Sajid Iqbal from the Imperial College London Diabetes Centre, Abu Dhabi, alongside an esteemed team of researchers, represents the first detailed report of inclisiran’s utilization in a real-world clinical setting within the Middle East North Africa (MENA) region. The retrospective review included 146 patients who commenced inclisiran between May 2021 and December 2022, examining its impact over a median follow-up period of 137 days.
Results
The data, derived from an outpatient diabetology, endocrinology, and cardiology center, indicates that inclisiran led to clinically meaningful reductions in pro-atherogenic lipids. Importantly, the medication was well-tolerated among the cohort. At 90 days, the median reduction in serum LDL-C was -37.9% for primary prevention patients and an impressive -54.1% for those in secondary prevention. LDL-C goals were achieved by 75.3% of the participants. Non-attainment of the LDL-C goal was primarily due to the system effect, followed by biological effect and discontinuation of treatment.
Discussion
This study provides compelling evidence that inclisiran, with its biannual dosing regimen, is not only efficacious but also highly tolerable. The reduction in LDL-C is particularly noteworthy considering the presence of a substantial proportion of diabetes mellitus patients, who are notoriously difficult to manage in terms of lipid levels due to the complex nature of their condition.
Safety Profile and Tolerability
With no patients discontinuing due to adverse events (AEs), inclisiran’s safety profile in a predominantly Arabic population remains consistent with previous safety reports. This finding reassures clinicians about the practical application of inclisiran in a diverse patient population.
Clinical Significance
The study stands out due to its optimal cohort, patient heterogeneity, and high retention rate, closely mirroring the benefits observed in randomized studies and open-label extension periods. The MENA region, with its unique genetic and lifestyle influences on CVD and lipid profiles, offers a fresh perspective on inclusive healthcare and therapeutic strategies.
Limitations
Recognizing its retrospective design and lack of a comparative group, the study does acknowledge selection bias as a limitation.
Conclusion
Iqbal and colleagues pave the way for enhanced management of hypercholesterolemia in real-world settings. These findings concerning inclisiran could mark a sea change in preventive cardiology, particularly for patients who are statin-intolerant or require additional LDL-C lowering.
Future Outlook
The horizon looks promising for inclisiran, with future studies poised to further elucidate its long-term benefits and potential impacts on cardiovascular morbidity and mortality.
Implications for Public Health
Enhancing the arsenal against hypercholesterolemia with inclisiran could translate into fewer heart attacks, strokes, and deaths, revolutionizing patient outcomes and overall public health within the region.
DOI
10.1016/j.clinthera.2023.12.003
References
1. Iqbal S, Sabbour HM, Ashraf T, Santos RD, Buckley A. First Report of Inclisiran Utilization for Hypercholesterolemia Treatment in Real-World Clinical Settings in a Middle East Population. Clin Ther. 2024 Jan 13. doi: 10.1016/j.clinthera.2023.12.003.
2. Ray KK, Landmesser U, Leiter LA, et al. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. N Engl J Med. 2017 Apr 13;376(15):1430-1440. doi: 10.1056/NEJMoa1615758.
3. Wright RS, Ray KK, Raal FJ, et al. Pooled Patient-Level Meta-Analysis of Inclisiran Trials for the Treatment of Hypercholesterolemia. Am J Cardiol. 2021 Jun 1;147:80-88. doi: 10.1016/j.amjcard.2021.03.013.
4. Stoekenbroek RM, Hartgers ML, Rutte R, et al. PCSK9 Inhibition by Inclisiran: A Novel Mechanism and Therapeutic Option for Managing Hypercholesterolemia. J Atheroscler Thromb. 2018;25(3):219-228. doi: 10.5551/jat.RV17018.
5. Raal FJ, Kallend D, Ray KK, et al. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Feb 20;382(8):1520-1530. doi: 10.1056/NEJMoa1913805.
Keywords
1. Inclisiran clinical study
2. Hypercholesterolemia treatment Middle East
3. LDL cholesterol reduction
4. Inclisiran real-world efficacy
5. siRNA-based hypercholesterolemia therapy
With these results, the promise of inclisiran in managing hypercholesterolemia becomes ever more tangible. Patients in the Middle East, particularly those with a genetic predisposition to high cholesterol levels or who have demonstrated intolerance to other lipid-lowering medications, now have a reason for optimism. The tireless efforts of the medical community continue to bear fruit, offering hope that the battle against cardiovascular diseases may soon encounter a significant breakthrough.
