Gemfibrozil decreases platelet reactivity in patients with hypercholesterolemia during physical stress

Laustiola, Kai; Lassila, Riitta; Koskinen, Pekka; Pellinen, Timo J.; Manninen, Vesa

doi:10.1038/clpt.1988.36

Cited by 19 publications

(8 citation statements)

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“…Other investigators have examined effects of gemfibrozil on platelet function and have found reduction of platelet retention (19) and platelet reactivity (20). However, no effect on platelet count or bleeding time has been recorded, which is in agreement with our results.…”

Section: Discussionsupporting

confidence: 93%

Effects of Gemfibrozil on Lipids and Haemostasis after Myocardial Infarction

et al. 1990

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SummaryThe effects of gemfibrozil on haemostatic variables were studied in 43 survivors of myocardial infarction with serum triglycerides (TG) ≥2 mmol/1 2 weeks prior to randomization. The study was double-blind, placebo-controlled and stratified for chronic betablockade. Twenty-two individuals were given gemfibrozil 600 mg twice daily and 21 individuals received matching placebo. After 8 weeks the TG level was unchanged in the placebo group, whereas a 44% reduction was noted in the gemfibrozil group (p <0.0001). Fibrinogen increased in both groups, while bleeding time and platelet count were unchanged. Clotting factor VH-phospholipid complex decreased in both groups, but the change was more marked and attained statistical significance only in the gemfibrozil group (60% reduction, p <0.01). By DDAVP-stimulated D-Dimer agglutination test 8 in 21 patients in the placebo group (38%) still had reduced fibrinolytic capacity versus none in the gemfibrozil group (p = 0.001). Thus, in this study, gemfibrozil improved reduced fibrinolytic capacity and may have reduced hypercoagulability by lowering the clotting factor VH-phospholipid complex.

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Section: Discussionsupporting

confidence: 93%

Effects of Gemfibrozil on Lipids and Haemostasis after Myocardial Infarction

et al. 1990

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“…Gemfibrozil has been shown to increase the fibrinolytic effect of plasma and decrease concentration of clotting factor VII-phospholipid complex in plasma, whereas in other studies no effect was seen [35][36][37]. Furthermore, the effects of gemfibrozil on platelet activity have been discrepant [38,39]. Thus, a pharmacodynamic interaction between gemfibrozil and warfarin cannot be excluded, although in our study gemfibrozil did not increase thromboplastin time measured before or after administration of warfarin.…”

Section: Figurecontrasting

confidence: 83%

Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of racemic warfarin in healthy subjects

Lilja

Backman

Neuvonen

2005

Brit J Clinical Pharma

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AimsCase reports suggest that gemfobrozil can increase the anticoagulant effect of warfarin. Because gemfibrozil inhibits CYP2C9 in vitro , we studied its effects on the pharmacokinetics and pharmacodynamics of racemic warfarin. MethodsIn a randomized cross-over study, 10 healthy subjects ingested 600 mg gemfibrozil or placebo twice daily for 8 days. On day 3, they were administered a single dose of 10 mg racemic R-S-warfarin orally. The concentrations of R-and S-warfarin in plasma and thromboplastin time were monitored up to 168 h. ResultsGemfibrozil decreased the mean ( ± SD) area under the plasma concentration-time curve [AUC (0-• ) ] of S-warfarin by 11%, from 19.9 ± 5.2 mg l -1 h to 17.6 ± 4.7 mg l -1 h (95% CI on the difference -3.7, -0.78; P < 0.01) and that of R-warfarin by 6% from 31.3 ± 7.5 mg l -1 h during the gemfibrozil phase to 29.5 ± 6.9 mg l -1 h during the placebo phase (95% CI -3.3, -0.33; P < 0.05). There were no significant differences in the elimination half-lives of S-or R-warfarin between the phases. Gemfibrozil did not alter the anticoagulant effect of warfarin. ConclusionUnexpectedly, gemfibrozil slightly decreased the plasma concentrations of R-and Swarfarin. Displacement of warfarin from plasma albumin by gemfibrozil or its interference with the absorption of warfarin could explain the present findings. Usual therapeutic doses of gemfibrozil seem to have limited effects on the pharmacokinetics and pharmacodynamics of single dose warfarin in healthy subjects.

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“…There is also some evidencethat fenofibrate can improveN Ob ioavailability (35). To our knowledge,f ibrates seem to be rather weak, if any, anti-plateleta gents (36).I nt he current study plateletactivity,asevidenced by β TG and P-selectin levels, wassignificantly reduced followingashort-termadministration of simvastatin, butn ot of fenofibrate, indicating that the latter did not exertany significant effect on platelet function during one month of the therapy. In the caseof β TG, the effect of simvastatin could be even strongerinsubjects not receiving aspirin, because aspiringiven for7daysdecreased significantly β TG levels in blood samples collected at the siteofmicrovasculari njury ( 37).…”

Section: Discussionmentioning

confidence: 46%

Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia

Undas¹,

Celińska-Löwenhoff²,

Domagała³

et al. 2005

Thromb Haemost

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The aim of the study was to determine whether a short-term treatment with simvastatin or fenofibrate may result in beneficial anti-inflammatory and antithrombotic effects in patients with high risk of coronary artery disease. In a randomized, double-blind study, we compared markers of inflammation, thrombin formation and platelet activation in patients with LDL cholesterol >130 mg/dl assigned to receive simvastatin (40 mg/d; n=20) or micronised fenofibrate (160 mg/d; n=22) for 28 days. Simvastatin, but not fenofibrate, lowered C-reactive protein (CRP) by 32% on day 3 (p<0.001), while both drugs reduced CRP significantly on day 28. Interleukin-6, soluble CD40 ligand, and monocyte chemoattractant protein-1 levels decreased significantly (by 20 to 50%) in both treatment groups on days 3 and 28. Soluble cell adhesion molecules remained unchanged in both groups. Simvastatin and fenofibrate significantly lowered plasma concentrations of thrombin-antithrombin complexes on days 3 and 28, but not platelet beta-thromboglobulin (betaTG) levels. Soluble P-selectin was lowered only in the simvastatin group. The total amount of thrombin generated at the site of microvascular injury also declined (by about 30%) as early as after 3 days of fenofibrate or simvastatin therapy, whereas beta TG release was reduced only in the simvastatin group on days 3 and 28. All the effects were independent of the changes in lipid profiles. Our results suggest that statins and fibrates can exert antithrombotic and anti-inflammatory effects as early as after 3 days of therapy. However, in contrast to statins, fibrates have no influence on platelet function within one month of therapy.

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Gemfibrozil decreases platelet reactivity in patients with hypercholesterolemia during physical stress

Cited by 19 publications

References 0 publications

Effects of Gemfibrozil on Lipids and Haemostasis after Myocardial Infarction

Effects of Gemfibrozil on Lipids and Haemostasis after Myocardial Infarction

Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of racemic warfarin in healthy subjects

Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia

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