Raaj Pawan Kumar Lingamgunta
NRI Medical College, IndiaPresentation Title:
Targeting elevated lipoprotein(a) with PCSK9 inhibitors: A new frontier in cardiovascular risk reduction- An Umbrella Review
Abstract
Background: Elevated Lipoprotein(a), a genetically inherited risk factor, is independently associated with increased cardiovascular risk. It remains underdiagnosed and undertreated in clinical practice, posing an unmet need in cardiovascular prevention. Unlike LDL-Cholestrol, lipoprotein(a) levels are not significantly influenced by diet or conventional lipid-lowering therapies such as statins. Recent studies suggest that Proprotein Convertase Subtilisin Kexin9 (PCSK9) inhibitors, initially developed for LDL-C reduction, may also reduce lipoprotein(a), offering dual benefits for patients with elevated lipoproteins(a) levels and high cardiovascular risk.
Methods: A comprehensive literature search was performed in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library, covering 2014 to 2024. Eleven systematic reviews and meta-analyses, comprising 253,311 participants, were selected based on predefined inclusion criteria. Cardiovascular risk reduction (hazard ratios) and Lp(a) reduction percentages were synthesized into standardized mean percentage change metrics. Data extraction and synthesis were performed independently by three reviewers. Participants aged 18 to 65 were studied from international centers and exhibited diverse cardiovascular risk profiles, Population characteristics were analyzed using pooled clinical trial data from different phases.
Results: Lp(a) reduction was analyzed in 11 studies with 253,311 participants. The mean reduction was 25.08% (95% CI:21.94%-28.21%), with reductions ranging from 10.91% to 30.60%. Sensitivity analysis confirmed a stabilized reduction of 26.5%. There was significant heterogeneity (I2 = 99.9%) and potential publication bias (Egger’s test, p = 0.001). Cardiovascular risk reduction was assessed in seven studies, yielding a pooled Hazard Ratio (HR) of 0.85 (95% CI: 0.75- 0.96, P = 0.008), representing a 15% reduction in Atherosclerotic Cardiovascular Disease (ASCVD) risk. Moderate heterogeneity (I2 = 72%) and possible publication bias (p=0.042) were noted.
Conclusions: PCSK9 inhibitors demonstrate a dual role, effectively decreasing both LDL-C and lipoprotein(a), which has a significant role in the primary prevention of cardiovascular events. By focusing on Lp(a) that is genetically raised, these drugs may help reduce the residual cardiovascular risk that is unmet by conventional lipid-lowering interventions. Yet, because of the heterogeneity and probable publication bias, many large and focused trials are needed to validate the data, optimize these interventions , and define clinical recommendations for Lp(a) treatment.
Biography
Raaj pawan Kumar is a final year MBBS student at Nri medical College, India with a strongacademic and research background. He has published one original research article and one case report in cureus with two additional manuscripts under review. He has presented at multiple conferences, including winning first prize for a case report at Kims Amalapuram 2024, and presenting a research paper on faecal microbita transplantation in ulcerative colitis at the same conference, 2025.
His primary area of interest is interventional cardiology driven by a commitment to advancing patient care through evidence based practice and innovation beyond academics. He has actively contributed to community service as a transitional readiness volunteer with Make Difference 2022 to 2023 and as a volunteer with Youth for Seva for two years. Passionate about education, Raaj has been teaching since his second year of MBBS and recently launched a start-up offering personalised teaching for first year MBBS students in Physiology, biochemistry and anatomy. He aims to integrate clinical excellence, research and mentorship in his future career fostering in the next generation of medical professionals.
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