Acute coronary syndromes, platelets and the endothelium

ABSTRACTBackground: Acute coronary syndromes (ACS) are medical emergencies. Platelet and endothelial function are fundamental to the pathophysiology; and implicated in secondary conditions such as no reflow (NR). Guidelines support the administration of P2Y12 antagonists in ACS treatment, but the broader effects are unclear.Objectives: 1) Assess the impact of P2Y12 inhibition (ticagrelor) on the platelet sensitivity to prostacyclin (PGI2) and nitric oxide (NO) in coronary artery disease (CAD). 2) Review NR and identify at risk patients 3) Outline the optimal P2Y12 antagonist in ACS patients with diabetes.Methods: 1) Platelet and endothelial function assessed at baseline and after 3 days oral ticagrelor in CAD patients. Multiple aspects of platelet activation and sensitivity to PGI2 and NO were examined by flow cytometry. 2) Prospective case-control study of STEMI patients with and without NR. Multiple regression identified independent predictors and a risk score established. 3) Meta-analysis of randomised trials with clinical outcomes for P2Y12 inhibitors in ACS patients with diabetes.Results: Ex vivo studies of CAD patients (n=63) demonstrated that oral ticagrelor induced only modest platelet inhibition in whole blood. However, it enhanced the inhibitory actions of PGI2 and NO. Ticagrelor potently amplified PGI2 inhibition of platelet-leukocyte aggregate formation (a measure of platelet inflammatory function). Ticagrelor improved endothelial reactive hyperaemic index (RHI), which correlated with platelet sensitivity. 24(13.9%) STEMI patients suffered NR, which significantly increased the risk of cardiovascular death. The independent predictors of NR were lesion complexity, systolic hypertension, weight<78kg, and history of hypertension. Systematic review of 7 studies, established newer P2Y12 antagonists (ticagrelor and prasugrel) were optimal for ACS patients with diabetes; with a trend to prasugrel superiority in the reduction of major adverse cardiovascular events.Conclusion: In patients with CAD, P2Y12 antagonism by ticagrelor promotes inhibition of platelet haemostatic and inflammatory function by endogenous regulators; and improves endothelial function

No-reflow phenomenon and comparison to the normal-flow population postprimary percutaneous coronary intervention for ST elevation myocardial infarction: case-control study (NORM PPCI)

Introduction No-reflow (NR) phenomenon is characterised by the failure of myocardial reperfusion despite the absence of mechanical coronary obstruction. NR negatively affects patient outcomes, emphasising the importance of prediction and management. The objective was to evaluate the incidence and independent predictors of NR in patients presenting with ST-elevation myocardial infarction (STEMI). Methods This was a single-centre prospective case-control study. Cases were subjects who suffered NR, and the control comparators were those who did not. Clinical outcomes were documented. Salient variables relating to the patients and their presentation, history and angiographical findings were compared using one-way analysis of variance or chi(2)test. Multiple regression determined the independent predictors, and a risk score was established based on the beta coefficient. Results Of 173 consecutive patients, 24 (13.9%) suffered from NR, with 46% occurring post stent implantation. Patients with NR had increased risk of in-hospital death (OR 7.0, 95% CI 1.3 to 36.7, p=0.022). From baseline variables available prior to percutaneous coronary intervention, the independent predictors of NR were increased lesion complexity, admission systolic hypertension, weight of &lt;78 kg and history of hypertension. Continuous data were transformed into best-fit binary variables, and a risk score was defined. Significant difference was demonstrated between the risk score of patients with NR (4.1 +/- 1) compared with controls (2.6 +/- 1) (p&lt;0.001), and the risk score was considered a good test (area under the curve=0.823). A score of &gt;= 4 had 75% sensitivity and 76.5% specificity. Conclusion Patients with NR have a higher rate of mortality following STEMI. Predictors of NR include lesion complexity, systolic hypertension and low weight. Further validation of this risk model is required