Review
Medicine, Research & Experimental
Grzegorz Grzesk, Bednarska Dorota, Lukasz Wolowiec, Anna Wolowiec, Joanna Osiak, Mariusz Kozakiewicz, Joanna Banach
Summary: 4 million people die from cardiovascular diseases annually in Europe due to atherosclerosis. Lowering LDL cholesterol level is the main therapeutic goal, but only 43% of statin-taking patients achieved their targets. PCSK9 inhibitors are a new group of lipid-lowering drugs that can reduce LDL-C level.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Cardiac & Cardiovascular Systems
Natalie Arnold, Wolfgang Koenig
Summary: This review critically summarizes the emerging cholesterol-lowering therapy targeting PCSK9, with a focus on the use of anti-PCSK9 monoclonal antibodies (mAbs) and inclisiran. Although both drug classes show similar efficacy in reducing LDL-C levels, the long-term safety and CV outcomes of inclisiran are still unknown.
CURRENT CARDIOLOGY REPORTS
(2022)
Article
Cardiac & Cardiovascular Systems
Michelle L. O'Donoghue, Robert P. Giugliano, Stephen D. Wiviott, Dan Atar, Anthony Keech, Julia F. Kuder, KyungAh Im, Sabina A. Murphy, Jose H. Flores-Arredondo, J. Antonio G. Lopez, Mary Elliott-Davey, Bei Wang, Maria Laura Monsalvo, Siddique Abbasi, Marc S. Sabatine
Summary: Long-term use of evolocumab to lower LDL-C levels is associated with low rates of adverse events, which do not exceed those in the placebo group. Over time, the use of evolocumab also leads to further reduction in cardiovascular events.
Article
Biochemistry & Molecular Biology
Rahayu Zulkapli, Suhaila Abd Muid, Seok Mui Wang, Hapizah Nawawi
Summary: This study aimed to investigate the effects of PCSK9 inhibitors on PCSK9, targeted early atherogenesis biomarkers, and monocyte binding in stimulated human coronary artery endothelial cells (HCAEC). The results showed that PCSK9 inhibitors exerted anti-atherogenic effects by downregulating PCSK9 and early atherogenesis biomarkers, as well as significantly inhibiting monocyte adhesion to endothelial cells via the NF-kappa B and eNOS pathways. These findings suggest the potential role of PCSK9 inhibitors in preventing atherosclerosis-related complications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Peripheral Vascular Disease
Ioanna Gouni-Berthold, Jonas Schwarz, Heiner K. Berthold
Summary: This review summarizes recent data on PCSK9 monoclonal antibodies and evaluates their relevance in the era of nucleic acid-based therapy for lipid lowering and prevention of cardiovascular disease. New methods of PCSK9 inhibition based on nucleic acid therapeutics are reported, and the clinical relevance of PCSK9 antibodies is discussed. Although other forms of PCSK9 inhibition are still in early phases of development, PCSK9-mAb remains the only tool with positive cardiovascular outcome trials.
CURRENT ATHEROSCLEROSIS REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Jelena Rakocevic, Milan Dobric, Rada Vucic, Matija Furtula, Ivan Zaletel, Katarina Milutinovic, Ana Ilijevski, Milica Labudovic Borovic, Miloje Tomasevic, Milos Bajcetic
Summary: The PCSK9 enzyme interferes with LDL cholesterol metabolism. Inhibiting PCSK9 lowers LDL cholesterol levels. Monoclonal antibodies targeting PCSK9 have shown strong and persistent effects, but require frequent subcutaneous injections. Inclisiran, a synthesized siRNA, inhibits PCSK9 synthesis and provides sustained LDL cholesterol lowering with twice-yearly applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
Douglas L. Jennings, Lina Sultan, Jennifer Mingov, Jason Choe, Farhana Latif, Susan Restaino, Kevin Clerkin, Marlena Habal, Paolo C. Colombo, Melana Yuzefpulskaya, Gabriel Sayer, Nir Uriel, William L. Baker
Summary: Coronary allograft vasculopathy (CAV) is a common problem in heart transplant recipients, and high LDL cholesterol is a major risk factor. Many patients cannot tolerate statin medications after transplantation, and there is limited data on alternative treatments. This study conducted a systematic review and meta-analysis to evaluate the safety and efficacy of PCSK9 inhibitors (PCSK9i) after heart transplantation. The results showed that PCSK9i use significantly reduced LDL cholesterol levels and had a favorable safety profile. Further studies with larger cohorts are needed to confirm these findings.
HEART FAILURE REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Haoyu Xiong, Rakesh N. Veedu, Sarah D. Diermeier
Summary: Oligonucleotide therapeutics show promising clinical outcomes in diseases such as Duchenne muscular dystrophy, familial amyloid neuropathies, and macular degeneration. Although no approved oligonucleotide drug exists for any type of cancer, results from preclinical studies and clinical trials are encouraging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Kausik K. Ray, Roel P. T. Troquay, Frank L. J. Visseren, Lawrence A. Leiter, R. Scott Wright, Sheikh Vikarunnessa, Zsolt Talloczy, Xiao Zang, Pierre Maheux, Anastasia Lesogor, Ulf Landmesser
Summary: This study aimed to assess the long-term effect of inclisiran on patients with high cardiovascular risk and elevated LDL cholesterol. The results showed that twice-yearly treatment with inclisiran resulted in sustained reductions in LDL cholesterol and was well tolerated over 4 years.
LANCET DIABETES & ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pere Rehues, Josefa Girona, Montse Guardiola, Nuria Plana, Roberto Scicali, Salvatore Piro, Ovidio Muniz-Grijalvo, Jose Luis Diaz-Diaz, Lluis Recasens, Marta Pinyol, Roser Rosales, Yaiza Esteban, Nuria Amigo, Lluis Masana, Daiana Ibarretxe, Josep Ribalta
Summary: This study evaluated the effects of iPCSK9 on glycoproteins A, B, and F, and found that iPCSK9 therapy not only reduced LDL cholesterol, but also decreased 1H-NMR glycoprotein signals, which correlated with a decrease in triglycerides and apoC-III.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
Stefania Angela Di Fusco, Aldo Pietro Maggioni, Chiara Bernelli, Francesco Perone, Vincenzo De Marzo, Edoardo Conte, Francesca Musella, Giuseppe Uccello, Leonardo De Luca, Domenico Gabrielli, Michele Massimo Gulizia, Fabrizio Oliva, Furio Colivicchi
Summary: Therapeutic approaches based on gene silencing technologies, such as inclisiran, have shown promise in managing hypercholesterolemia. Inclisiran effectively reduces LDL-C levels and is safe and well-tolerated. A meta-analysis of phase 3 trials demonstrated a significant reduction in LDL-C levels with inclisiran compared to placebo. Although patients receiving inclisiran may experience more reactions at the injection site, overall adverse event incidence is comparable to placebo.
REVIEWS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Cardiac & Cardiovascular Systems
Paul Guedeney, Sabato Sorrentino, Gennaro Giustino, Celine Chapelle, Silvy Laporte, Bimmer E. Claessen, Edouard Ollier, Anton Camaj, Deborah N. Kalkman, Birgit Vogel, Salvatore De Rosa, Ciro Indolfi, Benoit Lattuca, Michel Zeitouni, Mathieu Kerneis, Johanne Silvain, Jean-Philippe Collet, Roxana Mehran, Gilles Montalescot
Summary: This study compared the efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or established atherosclerotic cardiovascular disease. The results showed that there were no significant differences in efficacy endpoints between the two drugs, except for a better reduction in all-cause death with alirocumab. However, alirocumab had a higher risk of injection site reactions compared to evolocumab.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Yajnavalka Banerjee, Anca Pantea Stoian, Arrigo Francesco Giuseppe Cicero, Federica Fogacci, Dragana Nikolic, Alexandros Sachinidis, Ali A. Rizvi, Andrej Janez, Manfredi Rizzo
Summary: Inclisiran is a novel therapy that silences PCSK9 synthesis through RNA interference, effectively reducing LDL-C levels and lowering the risk for cardiovascular events. Clinical trials have shown its safety and efficacy, with injection-site reactions being more common than in the placebo group. Further studies are needed to ensure its specificity in targeting PCSK9 without affecting other physiological mRNAs.
EXPERT OPINION ON DRUG SAFETY
(2022)
Article
Cardiac & Cardiovascular Systems
Emil Hagstrom, P. Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Nicolas Danchin, Rafael Diaz, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Garen Manvelian, Robert Pordy, Michel Scemama, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz
Summary: This study investigated the predictive role of apolipoprotein B (apoB) levels in residual risk after acute coronary syndrome and found that apoB provides additional predictive information. The study also found that lowering apoB levels with the medication alirocumab can reduce cardiovascular events. Therefore, controlling apoB levels is important for reducing the risk after acute coronary syndrome.
Article
Pharmacology & Pharmacy
Morasa Sheikhy, Sarah J. Schrieber, Qin Sun, Victoria Gershuny, Murali K. Matta, Jane P. F. Bai, Xiulian Du, Giri Vegesna, Aanchal Shah, Kristin Prentice, Colleen Nalepinski, Issam Zineh, Yow-Ming Wang, David G. Strauss, Jeffry Florian
Summary: The FDA guidance on biosimilars development suggests that comparative clinical efficacy studies can be replaced by pharmacokinetic (PK) and pharmacodynamic (PD) similarity studies. However, there is a lack of PD comparability studies in biosimilar development, making it unclear how to plan these studies effectively.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)