-
Frontiers in Cardiovascular Medicine 2021Drugs can be classified as hydrophilic or lipophilic depending on their ability to dissolve in water or in lipid-containing media. The predominantly lipophilic statins... (Review)
Review
Drugs can be classified as hydrophilic or lipophilic depending on their ability to dissolve in water or in lipid-containing media. The predominantly lipophilic statins (simvastatin, fluvastatin, pitavastatin, lovastatin and atorvastatin) can easily enter cells, whereas hydrophilic statins (rosuvastatin and pravastatin) present greater hepatoselectivity. Although the beneficial role of statins in primary and secondary cardiovascular prevention has been unequivocally confirmed, the possible superiority of one statin or other regarding their solubility profile is still not well-established. In this respect, although some previously published observational studies and clinical trials observed a superiority of lipophilic statins in cardiovascular outcomes, these results could also be explained by a greater low-density lipoprotein cholesterol reduction with this statin type. On the other hand, previous studies reported conflicting results as to the possible superiority of one statin type over the other regarding heart failure outcomes. Furthermore, adverse events with statin therapy may also be related to their solubility profile. Thus, the aim of the present review was to collect clinical evidence on possible differences in cardiovascular outcomes among statins when their solubility profile is considered, and how this may also be related to the occurrence of statin-related adverse effects.
PubMed: 34095267
DOI: 10.3389/fcvm.2021.687585 -
Thrombosis Research Sep 2019Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL). The antibodies currently included in the... (Review)
Review
Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL). The antibodies currently included in the classification criteria include lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and anti-^2-glycoprotein 1 antibodies (^2GPI). APS can present with a variety of clinical phenotypes, including thrombosis in the veins, arteries and microvasculature and obstetrical complications. Pregnancy complications in obstetric APS (OAPS) include unexplained recurrent early pregnancy loss, fetal death, or premature birth due to severe preeclampsia, eclampsia, intrauterine growth restriction or other consequences of placental insufficiency. Careful, well monitored obstetric care with the use of aspirin and heparin has likely improved the pregnancy outcome in obstetric APS and currently approximately 70-80% of pregnant women with APS have a successful pregnancy outcome. However, the current standard of care does not prevent all pregnancy complications as the current treatment fails in 20-30% of APS pregnancies. Other treatments options are currently being explored and retrospective studies suggest that trials with hydroxychloroquine and possibly pravastatin are warranted in pregnant women with aPL. In this review will focus on the current treatment of OAPS.
Topics: Antiphospholipid Syndrome; Female; Humans; Pregnancy; Pregnancy Outcome
PubMed: 31477227
DOI: 10.1016/S0049-3848(19)30366-4 -
Expert Opinion on Drug Metabolism &... Sep 2020Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lower cholesterol synthesis in patients with hypercholesterolemia. Increased statin exposure is an... (Review)
Review
INTRODUCTION
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lower cholesterol synthesis in patients with hypercholesterolemia. Increased statin exposure is an important risk factor for skeletal muscle toxicity. Potent inhibitors of cytochrome P450 (CYP) 3A4 significantly increase plasma concentrations of the active forms of simvastatin, lovastatin, and atorvastatin. Fluvastatin is metabolized by CYP2C9, whereas pravastatin, rosuvastatin, and pitavastatin are unaffected by inhibition by either CYP. Statins also have different affinities for membrane transporters involved in processes such as intestinal absorption, hepatic absorption, biliary excretion, and renal excretion.
AREAS COVERED
In this review, the pharmacokinetic aspects of drug-drug interactions with statins and genetic polymorphisms of CYPs and drug transporters involved in the pharmacokinetics of statins are discussed.
EXPERT OPINION
Understanding the mechanisms underlying statin interactions can help minimize drug interactions and reduce the adverse side effects caused by statins. Since recent studies have shown the involvement of drug transporters such as OATP and BCRP as well as CYPs in statin pharmacokinetics, further clinical studies focusing on the drug transporters are necessary. The establishment of biomarkers based on novel mechanisms, such as the leakage of microRNAs into the peripheral blood associated with the muscle toxicity, is important for the early detection of statin side effects.
Topics: Animals; Carrier Proteins; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Muscle, Skeletal; Muscular Diseases; Pharmacogenetics; Polymorphism, Genetic
PubMed: 32729746
DOI: 10.1080/17425255.2020.1801634 -
European Heart Journal Jun 2020Lipoprotein(a) [Lp(a)] is elevated in 20-30% of people. This study aimed to assess the effect of statins on Lp(a) levels. (Meta-Analysis)
Meta-Analysis
AIMS
Lipoprotein(a) [Lp(a)] is elevated in 20-30% of people. This study aimed to assess the effect of statins on Lp(a) levels.
METHODS AND RESULTS
This subject-level meta-analysis includes 5256 patients (1371 on placebo and 3885 on statin) from six randomized trials, three statin-vs.-placebo trials, and three statin-vs.-statin trials, with pre- and on-treatment (4-104 weeks) Lp(a) levels. Statins included atorvastatin 10 mg/day and 80 mg/day, pravastatin 40 mg/day, rosuvastatin 40 mg/day, and pitavastatin 2 mg/day. Lipoprotein(a) levels were measured with the same validated assay. The primary analysis of Lp(a) is based on the log-transformed data. In the statin-vs.-placebo pooled analysis, the ratio of geometric means [95% confidence interval (CI)] for statin to placebo is 1.11 (1.07-1.14) (P < 0.0001), with ratio >1 indicating a higher increase in Lp(a) from baseline in statin vs. placebo. The mean percent change from baseline ranged from 8.5% to 19.6% in the statin groups and -0.4% to -2.3% in the placebo groups. In the statin-vs.-statin pooled analysis, the ratio of geometric means (95% CI) for atorvastatin to pravastatin is 1.09 (1.05-1.14) (P < 0.0001). The mean percent change from baseline ranged from 11.6% to 20.4% in the pravastatin group and 18.7% to 24.2% in the atorvastatin group. Incubation of HepG2 hepatocytes with atorvastatin showed an increase in expression of LPA mRNA and apolipoprotein(a) protein.
CONCLUSION
This meta-analysis reveals that statins significantly increase plasma Lp(a) levels. Elevations of Lp(a) post-statin therapy should be studied for effects on residual cardiovascular risk.
Topics: Atorvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoprotein(a); Pravastatin; Randomized Controlled Trials as Topic; Rosuvastatin Calcium
PubMed: 31111151
DOI: 10.1093/eurheartj/ehz310 -
Clinical Pharmacology and Therapeutics May 2022Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. Statin-associated musculoskeletal...
Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. Statin-associated musculoskeletal symptoms (SAMS) impact statin adherence and ultimately can impede the long-term effectiveness of statin therapy. There are several identified pharmacogenetic variants that impact statin disposition and adverse events during statin therapy. SLCO1B1 encodes a transporter (SLCO1B1; alternative names include OATP1B1 or OATP-C) that facilitates the hepatic uptake of all statins. ABCG2 encodes an efflux transporter (BCRP) that modulates the absorption and disposition of rosuvastatin. CYP2C9 encodes a phase I drug metabolizing enzyme responsible for the oxidation of some statins. Genetic variation in each of these genes alters systemic exposure to statins (i.e., simvastatin, rosuvastatin, pravastatin, pitavastatin, atorvastatin, fluvastatin, lovastatin), which can increase the risk for SAMS. We summarize the literature supporting these associations and provide therapeutic recommendations for statins based on SLCO1B1, ABCG2, and CYP2C9 genotype with the goal of improving the overall safety, adherence, and effectiveness of statin therapy. This document replaces the 2012 and 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for SLCO1B1 and simvastatin-induced myopathy.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Cytochrome P-450 CYP2C9; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Neoplasm Proteins; Pharmacogenetics; Rosuvastatin Calcium; Simvastatin
PubMed: 35152405
DOI: 10.1002/cpt.2557