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Platelet-related bi...
Platelet-related biomarkers and their response to inhibition with aspirin and p2y12-receptor antagonists in patients with acute coronary syndrome
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- Lowenstern, Angela (författare)
- Duke Univ, Med Ctr, Duke Clin Res Inst, DUMC Box 2845, Durham, NC 27710 USA.
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- Storey, Robert F. (författare)
- Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England.
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- Neely, Megan (författare)
- Duke Univ, Med Ctr, Duke Clin Res Inst, DUMC Box 2845, Durham, NC 27710 USA.
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- Sun, Jie-Lena (författare)
- Duke Univ, Med Ctr, Duke Clin Res Inst, DUMC Box 2845, Durham, NC 27710 USA.
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- Angiolillo, Dominick J. (författare)
- Univ Florida, Coll Med Jacksonville, Div Cardiol, Jacksonville, FL USA.
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- Cannon, Christopher P. (författare)
- Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
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- Himmelmann, Anders (författare)
- AstraZeneca Res & Dev, Gothenburg, Sweden.
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- Huber, Kurt (författare)
- Wilhelminen Hosp, Dept Med Cardiol & Intens Care 3, Vienna, Austria.;Sigmund Freud Private Univ, Sch Med, Vienna, Austria.
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- James, Stefan K., 1964- (författare)
- Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)
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- Katus, Hugo A. (författare)
- Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany.
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- Morais, Joao (författare)
- Leiria Hosp Ctr, Leiria, Portugal.
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- Siegbahn, Agneta, 1947- (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Klinisk kemi
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- Steg, Phillippe Gabriel (författare)
- Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;Paris Diderot Univ, Sorbonne Paris Cite, Paris, France.;NHLI Imperial Coll, ICMS, Royal Brompton Hosp, London, England.;FACT, INSERM, U1148, Paris, France.
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- Wallentin, Lars, 1943- (författare)
- Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)
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- Becker, Richard C. (författare)
- Univ Cincinnati, Coll Med, Heart Lung & Vasc Inst, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA.
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Duke Univ, Med Ctr, Duke Clin Res Inst, DUMC Box 2845, Durham, NC 27710 USA Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England. (creator_code:org_t)
- 2017-06-12
- 2017
- Engelska.
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 44:2, s. 145-153
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The PLATelet inhibition and patient Outcomes (PLATO) trial showed that treatment with ticagrelor reduced the rate of death due to vascular causes, myocardial infarction and stroke when compared to clopidogrel in patients with ST-elevation or non-ST-elevation acute coronary syndrome (ACS). While the comparative benefit of ticagrelor over clopidogrel increased over time, event rates accrued in both groups during the study period. The purpose of our biomarker-based exploratory analysis was to determine whether long-term platelet inhibition may be associated with platelet adaptation. A sample of 4000 participants from the PLATO trial also consented to participate in a prospectively designed biomarker substudy. Blood samples were procured at baseline, immediately prior to hospital discharge and at 1 and 6 months. Markers of platelet activity, including platelet count, serum CD40-ligand and soluble P-selectin were analyzed. Mean levels were compared at discharge, 1 and 6 months following study drug initiation-first for all patients and subsequently stratified by treatment group. A linear mixed model was used to estimate the short-term change rate (baseline to 1 month) and long-term change rate (1-6 months) for each biomarker. A Cox proportional hazards model was used to calculate hazard ratios for each change in biomarker over the two time periods examined: baseline to 1 month and 1 to 6 months. Prior to randomized treatment (baseline), sCD40 ligand and sP-selectin levels were elevated above the normal range of the assay (0.39 and 33.5 A μg/L, respectively). The mean level of each biomarker was significantly different at 1 month compared to baseline (p < 0.0001). When stratified by treatment group, at 1 month patients treated with ticagrelor had a larger increase in platelet count compared to those treated with clopidogrel (p < 0.0001). Similarly, when comparing biomarker levels for all patients at 6 months with those at 1 month, each differed significantly (p < 0.05). There was no significant difference between treatment groups during this time period. The rate of change for both platelet count and sP-selectin were significantly different between baseline and 1 month when compared to the 1 to 6-month time period (p < 0.0001). When comparing treatment groups, the rate of increase in platelets from baseline to 1 month was greater for patients treated with ticagrelor (p < 0.0001). This was no longer observed in the 1 to 6-month interval. Using a Cox proportional hazard model, the increase in platelet count from 1 to 6 months was associated with ischemic-thrombotic events, while sCD40 ligand decrease from 1 to 6 months was associated with hemorrhagic events. There were no differences between treatment groups for the associations with clinical endpoints. Dynamic changes in platelet count, sCD-40 ligand and sP-selectin occur over time among patients with ACS. Platelet-directed therapy with a P2Y12 receptor inhibitor in combination with aspirin modestly impacts the expression of these biomarkers. Platelet count and sCD40 ligand may offer modest overall predictive value for future ischemic-thrombotic or hemorrhagic clinical events, respectively. The existence of a platelet adaptome and its overall clinical significance among patients at risk for thrombotic events will require a more in-depth and platelet-biology specific investigation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- Acute coronary syndrome
- P2Y(12) inhibitor
- Ticagrelor
- Platelet adaptome
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Lowenstern, Ange ...
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Storey, Robert F ...
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Neely, Megan
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Sun, Jie-Lena
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Angiolillo, Domi ...
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Cannon, Christop ...
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Himmelmann, Ande ...
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Huber, Kurt
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James, Stefan K. ...
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Katus, Hugo A.
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Morais, Joao
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Siegbahn, Agneta ...
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Steg, Phillippe ...
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Wallentin, Lars, ...
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Becker, Richard ...
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