Impact of inflammatory state and metabolic control on responsiveness to dual antiplatelet therapy in type 2 diabetics after PCI: prognostic relevance of residual platelet aggregability in diabetics undergoing coronary interventions.
BACKGROUND
Type-2 diabetes is accompanied by a prothrombotic state influenced by endothelial dysfunction, inflammatory condition and platelet hyperreagibility. We aimed to characterize the relationship of inflammation and residual platelet aggregability (RPA) under antiplatelet therapy with regard to prognosis in an unselected PCI-cohort of diabetics.


METHODS
In a first step, a consecutive collective of 75 type 2 diabetics compared to 153 non-diabetic controls was evaluated at the time of PCI. Inflammatory markers, Interleukin 6 and C-reactive protein were measured by immunoassays. ADP and Aspirin assays were performed by multiple electrode aggregometry. Then, we consecutively evaluated ADP-induced RPA in 542 diabetics and 1,161 non-diabetics undergoing PCI and treated by standard antiplatelet therapy. Major CV-events were assessed at 30 days after PCI.


RESULTS
Inflammatory markers were significantly increased in diabetics with peri-interventional hyperglycemic state and inversely correlated with responsiveness to clopidogrel and aspirin. In a large scale cohort, diabetics showed a higher RPA compared to non-diabetics (median 38.1 vs. 28.8%; p < 0.001). After adjustment for relevant co-factors, diabetes remained a strong predictor for increased RPA (OR 4.39; 95% CI 1.95-6.83; p < 0.001). Furthermore, diabetics with high RPA had an increased risk for 30-day MI and CV-death than diabetics with low RPA (adjusted HR 1.05; 95% CI 1.02-1.07; p < 0.001).


CONCLUSIONS
We demonstrate that peri-interventional inflammatory degree and glycaemic control correlate with decreased antiplatelet drug responsiveness in diabetics. In addition, we identified high RPA as strong predictor for short-term CV-events in this group. Therefore, approaches to treat these entities are needed to improve outcome in diabetics undergoing PCI.
Geisler
Tobias
T
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany. t.geisler@rbht.nhs.uk
Mueller
Karin
K
Aichele
Simon
S
Bigalke
Boris
B
Stellos
Konstantinos
K
Htun
Patrick
P
Ninci
Elena
E
Fateh-Moghadam
Susanne
S
May
Andreas E
AE
Gawaz
Meinrad
M
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000628:therapy*; D003328:Coronary Thrombosis / Q000097:blood / Q000517:prevention & control; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000097:blood*; D008297:Male; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D010975:Platelet Aggregation Inhibitors; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin