The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome

Travis R. Sexton, Eric L. Wallace, Tracy E. Macaulay, Richard J. Charnigo, Virgilio Evangelista, Charles Campbell, Alison L. Bailey, Susan S. Smyth

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

In patients with acute coronary syndromes (ACS), early therapy with high-dose statins may reduce short-term adverse clinical outcomes. The mechanisms responsible are not known but could involve anti-inflammatory or anti-thrombotic effects. Compelling evidence from experimental models and clinical studies suggests that the interplay between inflammatory and thrombotic systems, typified by platelet–monocyte and platelet–neutrophil interactions, might be a key regulator of ischemic vascular events. The study sought to determine if early, high-dose administration of the HMG-CoA reductase inhibitor rosuvastatin in the setting of ACS exerts beneficial vascular effects by reducing, and inhibiting biomarkers of thromboinflammation, such as platelet-monocyte and platelet-neutrophil interactions, and biomarkers of myocardial necrosis. A total of 54 patients presenting with ACS within 8 h of symptom onset were randomized to rosuvastatin 40 mg or placebo. Rosuvastatin significantly reduced interactions between platelets and circulating neutrophils (P = 0.015) and monocytes (P = 0.009) within 24 h. No significant effects were observed on platelet aggregation or plasma levels of PF4, sP-selectin, or sCD40L, whereas significant reductions of RANTES occurred over time in both treatment groups. Plasma levels of myeloperoxidase (MPO) declined more rapidly with rosuvastatin therapy than placebo. In a subset of patients with normal cardiac necrosis biomarkers at randomization, rosuvastatin therapy was associated with less myocardial damage as measured by troponin-I or CK-MB. Early administration of high-dose statin therapy in patients with ACS appears to improve biomarkers of inflammation within 8 h, which may translate into fewer ischemic events.

Original languageEnglish (US)
Pages (from-to)186-195
Number of pages10
JournalJournal of Thrombosis and Thrombolysis
Volume39
Issue number2
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Acute Coronary Syndrome
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Biomarkers
Blood Platelets
Blood Vessels
Monocytes
Neutrophils
Necrosis
Placebos
Selectins
Chemokine CCL5
Troponin I
Therapeutics
Random Allocation
Secondary Prevention
Platelet Aggregation
Peroxidase
Anti-Inflammatory Agents
Theoretical Models
Rosuvastatin Calcium

All Science Journal Classification (ASJC) codes

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Sexton, T. R., Wallace, E. L., Macaulay, T. E., Charnigo, R. J., Evangelista, V., Campbell, C., ... Smyth, S. S. (2015). The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome. Journal of Thrombosis and Thrombolysis, 39(2), 186-195. https://doi.org/10.1007/s11239-014-1142-x

The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome. / Sexton, Travis R.; Wallace, Eric L.; Macaulay, Tracy E.; Charnigo, Richard J.; Evangelista, Virgilio; Campbell, Charles; Bailey, Alison L.; Smyth, Susan S.

In: Journal of Thrombosis and Thrombolysis, Vol. 39, No. 2, 01.01.2015, p. 186-195.

Research output: Contribution to journalArticle

Sexton, TR, Wallace, EL, Macaulay, TE, Charnigo, RJ, Evangelista, V, Campbell, C, Bailey, AL & Smyth, SS 2015, 'The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome', Journal of Thrombosis and Thrombolysis, vol. 39, no. 2, pp. 186-195. https://doi.org/10.1007/s11239-014-1142-x
Sexton, Travis R. ; Wallace, Eric L. ; Macaulay, Tracy E. ; Charnigo, Richard J. ; Evangelista, Virgilio ; Campbell, Charles ; Bailey, Alison L. ; Smyth, Susan S. / The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome. In: Journal of Thrombosis and Thrombolysis. 2015 ; Vol. 39, No. 2. pp. 186-195.
@article{106a7608a25d47c5b951bad66efe0719,
title = "The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome",
abstract = "In patients with acute coronary syndromes (ACS), early therapy with high-dose statins may reduce short-term adverse clinical outcomes. The mechanisms responsible are not known but could involve anti-inflammatory or anti-thrombotic effects. Compelling evidence from experimental models and clinical studies suggests that the interplay between inflammatory and thrombotic systems, typified by platelet–monocyte and platelet–neutrophil interactions, might be a key regulator of ischemic vascular events. The study sought to determine if early, high-dose administration of the HMG-CoA reductase inhibitor rosuvastatin in the setting of ACS exerts beneficial vascular effects by reducing, and inhibiting biomarkers of thromboinflammation, such as platelet-monocyte and platelet-neutrophil interactions, and biomarkers of myocardial necrosis. A total of 54 patients presenting with ACS within 8 h of symptom onset were randomized to rosuvastatin 40 mg or placebo. Rosuvastatin significantly reduced interactions between platelets and circulating neutrophils (P = 0.015) and monocytes (P = 0.009) within 24 h. No significant effects were observed on platelet aggregation or plasma levels of PF4, sP-selectin, or sCD40L, whereas significant reductions of RANTES occurred over time in both treatment groups. Plasma levels of myeloperoxidase (MPO) declined more rapidly with rosuvastatin therapy than placebo. In a subset of patients with normal cardiac necrosis biomarkers at randomization, rosuvastatin therapy was associated with less myocardial damage as measured by troponin-I or CK-MB. Early administration of high-dose statin therapy in patients with ACS appears to improve biomarkers of inflammation within 8 h, which may translate into fewer ischemic events.",
author = "Sexton, {Travis R.} and Wallace, {Eric L.} and Macaulay, {Tracy E.} and Charnigo, {Richard J.} and Virgilio Evangelista and Charles Campbell and Bailey, {Alison L.} and Smyth, {Susan S.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1007/s11239-014-1142-x",
language = "English (US)",
volume = "39",
pages = "186--195",
journal = "Journal of Thrombosis and Thrombolysis",
issn = "0929-5305",
publisher = "Springer Netherlands",
number = "2",

}

TY - JOUR

T1 - The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome

AU - Sexton, Travis R.

AU - Wallace, Eric L.

AU - Macaulay, Tracy E.

AU - Charnigo, Richard J.

AU - Evangelista, Virgilio

AU - Campbell, Charles

AU - Bailey, Alison L.

AU - Smyth, Susan S.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - In patients with acute coronary syndromes (ACS), early therapy with high-dose statins may reduce short-term adverse clinical outcomes. The mechanisms responsible are not known but could involve anti-inflammatory or anti-thrombotic effects. Compelling evidence from experimental models and clinical studies suggests that the interplay between inflammatory and thrombotic systems, typified by platelet–monocyte and platelet–neutrophil interactions, might be a key regulator of ischemic vascular events. The study sought to determine if early, high-dose administration of the HMG-CoA reductase inhibitor rosuvastatin in the setting of ACS exerts beneficial vascular effects by reducing, and inhibiting biomarkers of thromboinflammation, such as platelet-monocyte and platelet-neutrophil interactions, and biomarkers of myocardial necrosis. A total of 54 patients presenting with ACS within 8 h of symptom onset were randomized to rosuvastatin 40 mg or placebo. Rosuvastatin significantly reduced interactions between platelets and circulating neutrophils (P = 0.015) and monocytes (P = 0.009) within 24 h. No significant effects were observed on platelet aggregation or plasma levels of PF4, sP-selectin, or sCD40L, whereas significant reductions of RANTES occurred over time in both treatment groups. Plasma levels of myeloperoxidase (MPO) declined more rapidly with rosuvastatin therapy than placebo. In a subset of patients with normal cardiac necrosis biomarkers at randomization, rosuvastatin therapy was associated with less myocardial damage as measured by troponin-I or CK-MB. Early administration of high-dose statin therapy in patients with ACS appears to improve biomarkers of inflammation within 8 h, which may translate into fewer ischemic events.

AB - In patients with acute coronary syndromes (ACS), early therapy with high-dose statins may reduce short-term adverse clinical outcomes. The mechanisms responsible are not known but could involve anti-inflammatory or anti-thrombotic effects. Compelling evidence from experimental models and clinical studies suggests that the interplay between inflammatory and thrombotic systems, typified by platelet–monocyte and platelet–neutrophil interactions, might be a key regulator of ischemic vascular events. The study sought to determine if early, high-dose administration of the HMG-CoA reductase inhibitor rosuvastatin in the setting of ACS exerts beneficial vascular effects by reducing, and inhibiting biomarkers of thromboinflammation, such as platelet-monocyte and platelet-neutrophil interactions, and biomarkers of myocardial necrosis. A total of 54 patients presenting with ACS within 8 h of symptom onset were randomized to rosuvastatin 40 mg or placebo. Rosuvastatin significantly reduced interactions between platelets and circulating neutrophils (P = 0.015) and monocytes (P = 0.009) within 24 h. No significant effects were observed on platelet aggregation or plasma levels of PF4, sP-selectin, or sCD40L, whereas significant reductions of RANTES occurred over time in both treatment groups. Plasma levels of myeloperoxidase (MPO) declined more rapidly with rosuvastatin therapy than placebo. In a subset of patients with normal cardiac necrosis biomarkers at randomization, rosuvastatin therapy was associated with less myocardial damage as measured by troponin-I or CK-MB. Early administration of high-dose statin therapy in patients with ACS appears to improve biomarkers of inflammation within 8 h, which may translate into fewer ischemic events.

UR - http://www.scopus.com/inward/record.url?scp=84925533328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925533328&partnerID=8YFLogxK

U2 - 10.1007/s11239-014-1142-x

DO - 10.1007/s11239-014-1142-x

M3 - Article

VL - 39

SP - 186

EP - 195

JO - Journal of Thrombosis and Thrombolysis

JF - Journal of Thrombosis and Thrombolysis

SN - 0929-5305

IS - 2

ER -