Therapeutic pipeline in nonalcoholic steatohepatitis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 18(6), P. 373 - 392

Published: Feb. 10, 2021

Language: Английский

---

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Journal of Clinical Medicine, Journal Year: 2019, Volume and Issue: 9(1), P. 22 - 22

Published: Dec. 20, 2019

Statins are a cornerstone in the pharmacological prevention of cardiovascular disease. Although generally well tolerated, small subset patients experience statin-related myotoxicity (SRM). SRM is heterogeneous presentation; phenotypes include relatively more common myalgias, infrequent myopathies, and rare rhabdomyolysis. Very rarely, statins induce an anti-HMGCR positive immune-mediated necrotizing myopathy. Diagnosing clinical practice can be challenging, particularly for mild that frequently due to alternative aetiologies nocebo effect. Nevertheless, directly harm lead statin discontinuation/non-adherence, which increases risk events. Several factors increase systemic exposure predispose SRM, including advanced age, concomitant medications, nonsynonymous variant, rs4149056, SLCO1B1, encodes hepatic sinusoidal transporter, OATP1B1. Increased skeletal muscle mitochondrial dysfunction, calcium signalling disruption, reduced prenylation, atrogin-1 mediated atrophy pro-apoptotic signalling. Rare variants several metabolic myopathy genes CACNA1S, CPT2, LPIN1, PYGM RYR1 myopathy/rhabdomyolysis following exposure. The immune system implicated both conventional intolerance/myotoxicity via LILRB5 rs12975366, strong association exists between HLA-DRB1*11:01 Epigenetic (miR-499-5p, miR-145) have also been myotoxicity. remains challenge safe effective use statins, although consensus strategies manage proposed. Further research required, stringent phenotyping through N-of-1 trials coupled systems pharmacology omics- approaches identify novel provide mechanistic insight.

Language: Английский

---

Statin-Associated Myopathy: Emphasis on Mechanisms and Targeted Therapy

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11687 - 11687

Published: Oct. 28, 2021

Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Statins are the first-choice therapy dyslipidemias considered cornerstone of atherosclerotic disease (ASCVD) in both primary secondary prevention. Despite statin-therapy-mediated positive effects on events, patient compliance often poor. Statin-associated muscle symptoms (SAMS) most common side effect associated with treatment discontinuation. SAMS, which range from mild-to-moderate pain, weakness, or fatigue to potentially life-threatening rhabdomyolysis, reported by 10% 25% patients receiving statin therapy. There many factors features hypolipidemic agents that seem increase developing SAMS. Due lack “gold standard”, diagnostic test SAMS based clinical criteria score, independent creatine kinase (CK) elevation. Mechanisms underlie pathogenesis remain almost unclear, though high number may probability myotoxicity induced Some these, related pharmacokinetic properties statins concomitant therapies characteristics, affect bioavailability vulnerability high-dose statins.

Language: Английский

---

NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient

Journal of clinical lipidology, Journal Year: 2022, Volume and Issue: 16(4), P. 361 - 375

Published: June 9, 2022

Although statins are generally well tolerated, statin intolerance is reported in 5-30% of patients and contributes to reduced adherence persistence, as higher risk for adverse cardiovascular outcomes. This Scientific Statement from the National Lipid Association was developed provide an updated definition inform clinicians researchers about its identification management. Statin defined one or more effects associated with therapy which resolves improves dose reduction discontinuation can be classified a complete inability tolerate any partial necessary achieve patient-specific therapeutic objective. To classify patient having intolerance, minimum two should have been attempted, including at least lowest approved daily dosage. acknowledges importance identifying modifiable factors recognizes possibility "nocebo" effect (patient expectation harm resulting perceived side effects). identify tolerable regimen it recommended that consider using several different strategies (e.g., statin, dose, and/or dosing frequency). Non-statin may required who cannot reach objectives lifestyle maximal tolerated therapy. If so, therapies outcomes data randomized trials showing events favored. In high very intolerant, initiating non-statin while additional attempts made order limit time exposure elevated levels atherogenic lipoproteins.

Language: Английский

---

Statins Neuromuscular Adverse Effects

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8364 - 8364

Published: July 28, 2022

Statins are drugs widely prescribed in high-risk patients for cerebrovascular or cardiovascular diseases and are, usually, safe well tolerated. However, these sometimes may cause neuromuscular side effects that represent about two-third of all adverse events. Muscle-related events include cramps, myalgia, weakness, immune-mediated necrotizing myopathy and, more rarely, rhabdomyolysis. Moreover, they lead to peripheral neuropathy induce unmask a preexisting junction dysfunction. A clinical follow up assuming statins could reveal early damage suggest how better modulate their use. In fact, statin dechallenge cessation, the alternative use other lipid-lowering agents, can avoid This review summarizes current knowledge on statin-associated effects, diagnosis, management. It is conceivable incidence complications will increase because, nowadays, even diffused than past. On this purpose, it expected pharmacogenomic environmental studies help timely predict due exposure, leading personalized therapeutic approach.

Language: Английский

---

Cardiovascular Risk and Statin Therapy Considerations in Women

Diagnostics, Journal Year: 2020, Volume and Issue: 10(7), P. 483 - 483

Published: July 16, 2020

Despite major progress in the prevention and treatment of cardiovascular diseases, women remain an underdiagnosed insufficiently treated group, with higher hospitalization death rates compared to men. Obesity, more frequently encountered women, raises risk metabolic syndrome diseases as age. There are some differences based on sex regarding screening, diagnosis, dyslipidemia, it has been observed that less prescribed statins and, when they are, receive lower doses, even after myocardial infarction or coronary revascularization. Real-life data show that, men, at non-adherence statin predisposed discontinue because side effects. Statin metabolism particularities due a glomerular filtration rate, body fat percentage, overall faster metabolism. In fertile age, before initiating treatment, contraception methods should be discussed may have teratogenic Older likelihood polypharmacy, greater potential for drug interactions prescribing statin.

Language: Английский

---

Many Medicare Beneficiaries Do Not Fill High-Price Specialty Drug Prescriptions

Health Affairs, Journal Year: 2022, Volume and Issue: 41(4), P. 487 - 496

Published: April 1, 2022

For high-price drugs, Medicare Part D beneficiaries who do not receive a low-income subsidy must pay percentage of the drug’s price for each medication fill. Without that subsidy, which lowers out-of-pocket spending, typically hundreds or thousands dollars single We estimated proportion in fee-for-service Medicare, with and without initiate treatment (that is, fill new prescription) drugs newly prescribed four conditions. Examining 17,076 prescriptions issued between 2012 2018 from eleven geographically diverse health systems, we found receiving subsidies were nearly twice as likely to obtain drug within ninety days those subsidies. Among subsidies, observed noninitiation 30 percent written anticancer 22 hepatitis C treatments, more than 50 disease-modifying therapies either immune system disorders hypercholesterolemia. Our findings support current legislative efforts increase accessibility medications by reducing expenses under D, particularly

Language: Английский

---

A pragmatic guide for management of adverse events associated with lorlatinib

Lung Cancer, Journal Year: 2024, Volume and Issue: 191, P. 107535 - 107535

Published: March 15, 2024

Lorlatinib is a brain-penetrant, third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of anaplastic lymphoma (ALK)-positive metastatic non-small cell lung cancer (NSCLC). In clinical trials, lorlatinib has shown durable efficacy and manageable safety profile in treatment-naive patients those who have experienced progression while receiving first- and/or second-generation ALK TKIs. distinct from other TKIs, including hyperlipidemia central nervous system effects. Clinical trial data showed that most adverse events (AEs) can be managed effectively or reversed with dose modifications (such as interruptions reductions) concomitant medications without compromising quality life patients. A pragmatic approach to managing AEs related required. We present patient-focused recommendations evaluation management select associated developed by clinicians nurses extensive expertise routine practice. The follow general framework "prepare, monitor, manage, reassess" streamline AE assist practical, actionable, personalized patient care.

Language: Английский

---

VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeys

Journal of Lipid Research, Journal Year: 2024, Volume and Issue: 65(2), P. 100497 - 100497

Published: Jan. 10, 2024

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of burden in world and is highly correlated with chronic elevations low-density lipoprotein cholesterol (LDL-C). LDL-C lowering drugs such as statins or monoclonal antibodies (mAbs) against proprotein convertase subtilisin/kexin type 9 (PCSK9) are known to reduce risk diseases, however associated limited efficacy poor adherence treatment, whereas PCSK9 inhibitors only prescribed a “high risk” patient population those who have failed other therapies. Based on proven safety profile existing antibodies, we developed peptide-based vaccine PCSK9, VXX-401, an alternative option treat hypercholesterolemia prevent ASCVD. VXX-401 designed trigger safe humoral immune response resulting production endogenous subsequent 30 40% reduction blood LDL-C. In this paper, demonstrates robust immunogenicity sustained serum effects non-human primates (NHP). Additionally, induced by bind human high affinity block inhibitory effect uptake hepatic cell model. A repeat-dose toxicity study conducted NHP under good laboratory practices (GLP toxicity) indicated suitable tolerability profile, injection site reactions being main findings. As promising effective therapy, may represent broadly accessible convenient

Language: Английский

---

The protective effect of coadministration of coenzyme Q10 and vitamin E on myopathy induced by simvastatin in rats

Toxicology Reports, Journal Year: 2025, Volume and Issue: 14, P. 101942 - 101942

Published: Jan. 31, 2025

Language: Английский

---