PMID- 31910903
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20210317
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 19
IP  - 1
DP  - 2020 Jan 7
TI  - Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes 
      mellitus: a double-blind randomised controlled trial of the effects on thrombotic 
      markers and microRNA levels.
PG  - 3
LID - 10.1186/s12933-019-0981-3 [doi]
LID - 3
AB  - BACKGROUND: Despite increased atherothrombotic risk in type 2 diabetes mellitus, 
      (T2DM) the best preventative antithrombotic strategy remains undetermined. We 
      defined the effects of three antiplatelet agents on functional readout and 
      biomarker kinetics in platelet activation and coagulation in patients with T2DM. 
      MATERIALS AND METHODS: 56 patients with T2DM were randomised to antiplatelet 
      monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 
      10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was 
      determined by light-transmittance aggregometry and P-selectin expression by flow 
      cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were 
      measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase 
      chain reactions. RESULTS: Of the 56 patients, 24 (43%) were receiving aspirin for 
      primary prevention of ischaemic events and 32 (57%) for secondary prevention. 
      Prasugrel was the strongest inhibitor of ADP-induced PA (mean +/- SD maximum 
      response to 20mumol/L ADP 77.6 +/- 8.4% [aspirin] vs. 57.7 +/- 17.6% [clopidogrel] vs. 
      34.1 +/- 14.1% [prasugrel], p < 0.001), P-selectin expression (30 mumol/L ADP; 
      45.1 +/- 21.4% vs. 27.1 +/- 19.0% vs. 14.1 +/- 14.9%, p < 0.001) and collagen-induced 
      PA (2 mug/mL; 62.1 +/- 19.4% vs. 72.3 +/- 18.2% vs. 60.2 +/- 18.5%, p < 0.001). Fibrin 
      clot dynamics and levels of coagulation and inflammatory proteins were similar. 
      Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and 
      miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. 
      Circulating miR-197 was lower in those cardiovascular disease during therapy with 
      aspirin (p = 0.039) or prasugrel (p = 0.0083). CONCLUSIONS: Prasugrel monotherapy 
      in T2DM provided potent platelet inhibition and reduced levels of a number of 
      platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular 
      disease in this population. Clinical outcome studies investigating prasugrel 
      monotherapy are warranted in individuals with T2DM. Trial registration EudraCT, 
      2009-011907-22. Registered 15 March 2010, 
      https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB.
FAU - Parker, William A E
AU  - Parker WAE
AUID- ORCID: 0000-0002-7822-8852
AD  - Department of Infection, Immunity & Cardiovascular Disease, University of 
      Sheffield, Sheffield, UK.
FAU - Schulte, Christian
AU  - Schulte C
AD  - King's British Heart Foundation Centre, King's College London, London, UK.
AD  - Department of General and Interventional Cardiology, University Heart Centre 
      Hamburg Eppendorf, Hamburg, Germany.
FAU - Barwari, Temo
AU  - Barwari T
AD  - King's British Heart Foundation Centre, King's College London, London, UK.
FAU - Phoenix, Fladia
AU  - Phoenix F
AD  - Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, 
      Leeds, UK.
FAU - Pearson, Sam M
AU  - Pearson SM
AD  - Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, 
      Leeds, UK.
FAU - Mayr, Manuel
AU  - Mayr M
AD  - King's British Heart Foundation Centre, King's College London, London, UK.
FAU - Grant, Peter J
AU  - Grant PJ
AD  - Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, 
      Leeds, UK.
FAU - Storey, Robert F
AU  - Storey RF
AD  - Department of Infection, Immunity & Cardiovascular Disease, University of 
      Sheffield, Sheffield, UK.
FAU - Ajjan, Ramzi A
AU  - Ajjan RA
AD  - Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, 
      Leeds, UK. R.Ajjan@leeds.ac.uk.
LA  - eng
SI  - EudraCT/EudraCT 2009-011907-22
GR  - SP/17/10/33219/BHF_/British Heart Foundation/United Kingdom
GR  - FS/18/49/33752/BHF_/British Heart Foundation/United Kingdom
GR  - RG/16/14/32397/BHF_/British Heart Foundation/United Kingdom
GR  - CH/16/3/32406/BHF_/British Heart Foundation/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200107
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Biomarkers)
RN  - 0 (MicroRNAs)
RN  - 0 (P-Selectin)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (SELP protein, human)
RN  - 9001-31-4 (Fibrin)
RN  - A74586SNO7 (Clopidogrel)
RN  - G89JQ59I13 (Prasugrel Hydrochloride)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Aged
MH  - Aspirin/adverse effects/*therapeutic use
MH  - Biomarkers/blood
MH  - Blood Coagulation/*drug effects
MH  - Clopidogrel/adverse effects/*therapeutic use
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy
MH  - Double-Blind Method
MH  - Female
MH  - Fibrin/metabolism
MH  - Humans
MH  - Male
MH  - MicroRNAs/blood
MH  - Middle Aged
MH  - P-Selectin/blood
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Aggregation Inhibitors/adverse effects/*therapeutic use
MH  - Prasugrel Hydrochloride/adverse effects/*therapeutic use
MH  - Primary Prevention
MH  - Secondary Prevention
MH  - Thrombosis/blood/diagnosis/*prevention & control
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC6945631
OTO - NOTNLM
OT  - Aspirin
OT  - Diabetes mellitus
OT  - Micro RNA
OT  - P2Y12 inhibitors
OT  - Platelet inhibition
COIS- M Mayr filed and licensed patent applications on miRNAs as biomarkers 
      (EP15193448.6, EP2776580 B1, DE112013006129T5, GB2524692A, EP2576826 B, 
      JP2013-513740). M. Mayr filed and licensed patent applications on miRNAs as 
      biomarkers (EP15193448.6, EP2776580 B1, DE112013006129T5, GB2524692A, EP2576826 
      B, JP2013-513740). RF Storey reports institutional research grants/support from 
      AstraZeneca and GlyCardial Diagnostics; consultancy fees from Amgen, AstraZeneca, 
      Bayer, Bristol Myers Squibb/Pfizer, GlyCardial Diagnostics, Haemonetics, Idorsia, 
      Novartis, Portola and Thromboserin; and honoraria from AstraZeneca, Bayer, 
      Bristol Myers Squibb/Pfizer and Medscape. R. Ajjan. received honoraria and 
      educational and research support from Abbott Diabetes Care, AstraZeneca, Novo 
      Nordisk, Eli Lilly, Bayer, Sanofi, MSD, and Boehringer Ingelheim. The other 
      authors report no relevant disclosures.
EDAT- 2020/01/09 06:00
MHDA- 2020/09/01 06:00
PMCR- 2020/01/07
CRDT- 2020/01/09 06:00
PHST- 2019/11/10 00:00 [received]
PHST- 2019/12/26 00:00 [accepted]
PHST- 2020/01/09 06:00 [entrez]
PHST- 2020/01/09 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2020/01/07 00:00 [pmc-release]
AID - 10.1186/s12933-019-0981-3 [pii]
AID - 981 [pii]
AID - 10.1186/s12933-019-0981-3 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2020 Jan 7;19(1):3. doi: 10.1186/s12933-019-0981-3.