Simvastatin administration reduces thromboxane production in subjects taking aspirin: Links between aspirin resistance and thrombin generation

Undas, Anetta; Siudak, Zbigniew; Leśniak, Marta; Tracz, Wiesława

doi:10.1016/j.ijcard.2010.09.093

Cited by 12 publications

(6 citation statements)

References 28 publications

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“…As previously mentioned, statins are able to reduce the so-called “aspirin resistance”, a phenomenon associated with adverse cardiovascular outcomes and increased mortality [ 26 ]. Actually, in our study simvastatin therapy showed the ability to significantly improve the in vitro platelet sensitivity to the antiaggregating effects of aspirin, a finding consistent with data obtained by other authors showing a reduced TXA 2 formation in patients treated with simvastatin and receiving aspirin before and after statin administration [ 28 ].…”

Section: Discussionsupporting

confidence: 92%

“…From the biochemical point of view, elevated cholesterol reduces the aspirin-mediated platelet acetylation, a mechanism involved in the aspirin-induced antiaggregating effect, exerted via the irreversible inhibition of TXA 2 biosynthesis [ 27 ]. Therapy with statins is able to significantly reduce platelet TXA 2 formation in patients taking low dose of aspirin [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia

Barale

Frascaroli

Senkeev

et al. 2018

BioMed Research International

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Background Beside the lipid-lowering effect, statins slow the progression of atherosclerosis by exerting anti-inflammatory and platelet inhibiting effects. We investigated whether platelet inhibition by simvastatin correlates with the statin effects on lipid lowering, inflammation, oxidative stress, and endothelial and platelet activation. MethodsIn hypercholesterolemic patients allocated to diet (n=20) or a 2-month treatment with diet plus 40 mg simvastatin (n=25), we evaluated platelet aggregating responses to ADP, collagen, and arachidonic acid (AA), the effect of aspirin on AA-induced aggregation, pro- and anti-inflammatory and atherogenic mediators (IL-1β, -5, -6, -7, -8, -9, -10, -12, and -13, IFN-γ, IP-10, Eotaxin, and sRAGE), markers of endothelium (sE-selectin, VEGF, and MCP-1) and platelet activation (sP-selectin, sCD-40L, RANTES, and PDGF-bb), and oxidative stress (8-OH-2'-deoxyguanosine). Results After treatment, beside the improvement of lipid profile, we observed the following: a reduction of platelet aggregation to ADP (p=0.0001), collagen (p=0.0001), AA (p=0.003); an increased antiaggregating effect of aspirin in the presence of AA (p=0.0001); a reduction of circulating levels of IL-6 (p=0.0034), IL-13 (p<0.0001), IFN-γ (p<0.0001), VEGF (p<0.0001), sE-selectin (p<0.0001), sCD-40L (p<0.0001), sP-selectin (p=0.003), and 8-OH-2'-deoxyguanosine (p<0.0001); an increase of IL-10 and sRAGEs (p=0.0001 for both). LDL-cholesterol levels (i) positively correlated with IL-6, IFN-γ, E-selectin, sCD-40L, 8-OH-2'-deoxyguanosine, platelet aggregation to ADP, collagen, AA, and aspirin IC-50 and (ii) negatively correlated with IL-10 and sRAGE. In multiple regression analyses, LDL-cholesterol was the strongest predictor for most parameters of platelet reactivity. Conclusion In primary hypercholesterolemia, simvastatin treatment reduced platelet activation and subclinical inflammation and improved endothelial dysfunction. LDL-cholesterol levels were the major correlate of platelet reactivity; however, other effects of statins may contribute to reducing the progression of atherosclerosis.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia

Barale

Frascaroli

Senkeev

et al. 2018

BioMed Research International

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“…There were prior reports about statin therapy reducing platelet TXA2 synthesis. 11,12 A prior study, using PFA-100, demonstrated high-dose statin therapy improved aspirin resistance in patients with coronary artery disease, with concomitant decrease inLDL-C. 13 However, studies in the correlations between aspirin resistance, statin therapy, and LDL level were not consistent. Another study showed statin add-on aspirin-treated patients might improve platelet sensitivity but beyond the action of lipid lowing.…”

Section: Discussionmentioning

confidence: 99%

Associations Between PFA-Measured Aspirin Resistance, Platelet Count, Renal Function, and Angiotensin Receptor Blockers

Chen

Chou²

2018

Clin Appl Thromb Hemost

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Aspirin resistance is used to describe patients who are undergoing aspirin therapy but fail for the inhibition of thromboxane biosynthesis in platelets. Although the true mechanism is unclear, drug-drug interaction remains a possible factor. The study aimed to determine whether there was association between aspirin resistance and the concomitant cardiovascular medication. Using the Platelet Function Analyzer-100 system, aspirin resistance was evaluated in aspirin-treated patients from the outpatient department. The associations between aspirin resistance and their concomitant common cardiovascular medication were analyzed. Aspirin resistance was prevalent in 147 (17.7%) of 831 patients. Concomitant angiotensin receptor blocker (ARB) treatment and low platelet count were associated with aspirin response ( P = .04, .02, respectively). Multivariate logistic regression analysis results showed an association between aspirin response and ARB therapy (adjusted odds ratio [OR] 1.48; 95% confidence interval, CI: 1.08-2.18). And the association was blunted when platelet count was considered (adjusted OR 1.43, 95% CI: 0.92-2.23). In ARB-treated patients, increased creatinine and decreased hematocrit laboratory data increased the risk of aspirin resistance ( P = .02, .04, respectively), and the effect of platelet count on aspirin resistance was diminished by ARB therapy. Concomitant ARB treatment in aspirin-treated patients decreased the risk of aspirin resistance, and the effect was dependent on low platelet count. In ARB-treated patients, increased creatinine and decreased hematocrit data increased the risk of aspirin resistance. In addition, the effect of platelet count on aspirin resistance was diminished by ARB treatment.

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“…In addition, Undas et al. [14] showed that simvastatin significantly reduced platelets TxA 2 formation in patients taking low‐dose aspirin, and this effect was associated with attenuated thrombin formation in response to vascular injury. Our results indicate that simvastatin or pravastatin may directly interact with blood platelets and downregulate the activation of GPIIb‐IIIa, as well as platelet aggregation and collagen‐dependent thromboxane generation in platelets treated with aspirin.…”

Section: Discussionmentioning

confidence: 99%

Pravastatin and simvastatin improves acetylsalicylic acid‐mediated in vitro blood platelet inhibition

Luzak

Rywaniak

Stanczyk

et al. 2012

Eur J Clin Investigation

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Our results suggested that statins may directly interact with platelet membranes or may modulate a signalling pathway in platelets (the pleiotropic effects of statins). It is possible that the statin effect on CD36 and ASA-mediated protein acetylation can be reached by the modulation of a distribution or a function of membrane-associated proteins. Further studies are certainly needed to better elucidate the mechanism(s) underlying the statins' effects on platelet sensitivity to ASA.

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Simvastatin administration reduces thromboxane production in subjects taking aspirin: Links between aspirin resistance and thrombin generation

Cited by 12 publications

References 28 publications

Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia

Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia

Associations Between PFA-Measured Aspirin Resistance, Platelet Count, Renal Function, and Angiotensin Receptor Blockers

Pravastatin and simvastatin improves acetylsalicylic acid‐mediated in vitro blood platelet inhibition

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