Effects of simvastatin on tissue factor pathway of blood coagulation in STATCOPE (Simvastatin in the prevention of COPD exacerbations) trial

Abstract

Background Statins are widely used to lower lipids and reduce cardiovascular events. In vitro studies and small studies in patients with hyperlipidemias show statins inhibit tissue factor (TF) and blood coagulation mechanisms. We assessed the effects of simvastatin on TF and coagulation biomarkers in patients entered in STATCOPE, a multicenter, randomized, placebo‐controlled trial of simvastatin (40 mg daily) versus placebo on exacerbation rates in patients with chronic obstructive pulmonary disease (COPD). Methods In 227 patients (114 simvastatin, 113 placebo; mean [± standard error of the mean] age 62 ± 0.53 years, 44.5% women) we measured (baseline, and 6 and 12 months): whole blood membrane TF‐procoagulant activity (TF‐PCA) and plasma factors VIIa, VII, VIII, fibrinogen, TF antigen, tissue factor pathway inhibitor (TFPI), thrombin‐antithrombin complexes (TAT), and D‐dimer. We excluded patients with diabetes, cardiovascular disease, and those taking or requiring a statin. Results In the statin group, there was a small increase in TF‐PCA (from 25.18 ± 1.08 to 30.36 ± 1.10 U/ml; p = .03) over 12 months; factors VIIa and VIII, fibrinogen, TAT, and D‐dimer did not change. Plasma TFPI (from 52.4 ± 1.75 to 44.7 ± 1.78 ng/ml; p < .0001) and FVIIC (1.23 ± 0.04 to 1.15 ± 0.03 U/ml; p = .03) decreased and correlated with total cholesterol levels. No changes in biomarkers were observed with placebo. Conclusions In contrast to previous studies on statins, in COPD patients without diabetes, cardiovascular disease, or requiring a statin treatment, simvastatin (40 mg per day) did not decrease TF or factors VIIa and VIII, fibrinogen, TAT, or D‐dimer. The decreases in TFPI and factor VII reflect the decrease in serum lipids.

The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma

“…As mentioned, statins are inhibitors of the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase [41]. They also have additional effects, including on the circulatory system, by affecting endothelial function [41,42], stabilizing atherosclerotic plaques [43,44], inhibiting the coagulation system [45,46], stimulating the fibrinolysis system [47], or inhibiting inflammatory reactions, and immunomodulatory effects [48,49]. Statins reduce the number of coronary events, strokes, revascularization procedures, and deaths caused by coronary artery disease [49,50].…”

Statins—From Fungi to Pharmacy

“…Selected clinical trials regarding the beneficial and pleiotropic effects of statins are presented in Table 2. reduction of LDL cholesterol level/NCT03242499 [111], NCT04359823 [112] the effect on synaptic plasticity, cognitive function, and attention in patients with RASopathies/NCT03504501 [113] improvement in the treatment of diffuse superficial actinic porokeratosis/NCT04359823 [112] modulation of cortical inhibition in neurofibromatosis type 1 (NF1)/NCT03826940 [114] reduction of motor symptoms in patients with early-stage Parkinson's/NCT03242499 [111] pravastatin reduction of LDL cholesterol level/ACTRN12616000535471 [115] prevention of pre-eclampsia in pregnant women/NCT01717586 [116] biomarker for monitoring the clinical benefit of statin treatment in secondary prevention/ ACTRN12616000535471 [115] prevention of the occurrence of atherothrombotic brain infarction in noncardioembolic infarction patients/NCT00361530 [117] reducing the incidence of lacunar stroke/NCT00221104 [118] reduction in levels of lipoprotein subclasses/NCT03073018 [119] reduction of vascular inflammation in non-cardiogenic ischemic stroke/NCT00361699 [120] simvastatin inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase/ NCT00529139 [121] reduction in serum LDL concentration/NCT00939822 [122], NCT01061671 [123] activation of PI3K-kinase/NCT00676897 [121] positive effect on emotions/NCT04652089 [124] improved survival in ever-smokers with extensive disease (ED)-small cell lung cancer (SCLC)/NCT01441349 [125] reductions in total cholesterol, lipoprotein, and triglycerides observed in children with type 1 diabetes mellitus/NCT03660293 [126] anti-inflammatory and neuroprotective effects/NCT01999309 [127] prevention of decompensation in patients with compensated cirrhosis/NCT03654053 [128] Type II-synthetically derived statins fluvastatin reduction in blood lipid levels/ ChiCTR-TRC-12002642 [129] decrease in LDL-level/NCT00421005 [130] decrease of inflammatory index, ultrasonic index and electrocardiographic measurement results in atrial fibrillation/ChiCTR-TRC-12002642 [129] normalization of bilirubin levels and reduced blood ...…”

Development and Evaluation of Self-Emulsifying Drug-Delivery System–Based Tablets for Simvastatin, a BCS Class II Drug

“…Simvastatin ( Figure 1 ) is a competitive inhibitor of the enzyme HMG CoA reductase and is used to decrease low–density lipoprotein cholesterol in the blood. 19 It has poor water solubility and has been classified as a class II drug based on BCS, with a pKa value of 4.68. 20 , 21 Being a BCS class II drug, its oral bioavailability depends upon its dissolution rate from the solid dosage form.…”