Digital archive of theses discussed at the University of Pisa


Thesis etd-11222019-122818

Thesis type
Tesi di specializzazione (5 anni)
Thesis title
Prehospital antithrombotic strategy with crushed ticagrelor in patients with ST-elevation myocardial infarction: Results of the PISTOIA Study
Course of study
relatore Prof. Pedrinelli, Roberto
relatore Dott. Comeglio, Marco
relatore Prof.ssa Petronio, Anna Sonia
  • pretrattamento
  • infarto miocardico acuto
  • cardiopatia ischemica
  • stemi
  • ticagrelor
Graduation session start date
Release date
Background: In patients with ST-elevation acute myocardial infarction (STEMI), the effect of oral P2Y12 receptor antagonists is delayed, with subsequent increased risk of early thrombotic complications during primary percutaneous coronary intervention (P-PCI). Pre-hospital administration of ticagrelor reduced the incidence of early stent thrombosis, but did not improve pre-P-PCI coronary reperfusion, compared to peri-procedural administration. Evidence exists that a pulverized (crushed) formulation of ticagrelor is associated with increased bioavailability and a prompter platelet inhibition compared to integral tablets. To date, we have no data on the pharmacodynamic (PD) and clinical effects of a pre-hospital antithrombotic strategy (crushed ticagrelor plus aspirin and unfractionated heparin), in patients with STEMI undergoing P-PCI.

Methods: We conducted a monocentric, observational, prospective study, involving 35 patients with pre-hospital diagnosis of STEMI undergoing P-PCI. All patients were treated in the ambulance with a loading dose (180 mg) of crushed ticagrelor, together with acetylsalicylic acid (ASA: 300 mg i.v.) and unfractionated heparin (70 U/Kg i.v.). The use of morphine was discouraged. PD analyses were carried out on blood samples obtained at the time of diagnosis (T-D), at the beginning of P-PCI (T-PCI) and two hours after enrollment (T-2H). The effect on platelet function was measured as P2Y12 reaction units (PRU) by VerifyNow system. Study patients were compared with matched historical controls treated with integral ticagrelor in the catherization laboratory (CL). The primary objective was to assess the proportion of patients with adequate platelet inhibition at the beginning of P-PCI. Surrogate endpoints were pre-PCI myocardial reperfusion, evaluated both as rate of ST-resolution and as TIMI flow in the culprit coronary artery.

Results: The pre-hospital antithrombotic strategy with crushed ticagrelor LD, resulted in significant platelet inhibition at the beginning of P-PCI (PRU: T-D 279±41 vs T-PCI 182±79, p<0.001). An adequate platelet inhibition at the beginning of P-PCI was observed in over 60% of patients. Compared to controls, there was a significant PRU reduction both at the time of P-PCI (T-PCI: 182±79 vs 284±50, p<0.001) and at T-2h point (111±79 vs 160±112, p<0.006). A positive trend in pre-PCI myocardial reperfusion indicators was observed with the pre-hospital strategy (TIMI ≥ 2 in 41% of cases vs 12% in controls; p<0.05). A TIMI III flow was documented in 33.3% vs 3% of cases (P<0.05).

Conclusions: In patients with STEMI undergoing P-PCI, a pre-hospital antithrombotic strategy with crushed ticagrelor plus aspirin and heparin, resulted in adequate platelet inhibition at the beginning of P-PCI in almost 2/3 of patients. Compared to peri-procedural administration a positive trend in myocardial reperfusion indicators was also observed.

What do these data add to what is already known

1)Pistoia study is the first trial to evaluate the effect of complete pre-hospital administration of evidence-based antithrombotic treatment (ASA, UFH and ticagrelor), with crushed formulation of the P2Y12 receptor antagonist, on platelet inhibition at the beginning of P-PCI
2)Although our study was not powered for clinical outcomes, HPR rates, a surrogate marker of thrombotic complications, were markedly decreased at the time of P-PCI when compared to baseline and to peri-procedural administration strategy with integral ticagrelor tablets
3)In our study there was a positive trend in myocardial reperfusion indicators and a better TIMI flow in the infarct related artery at the initial angiography, which is associated with lower stent thrombosis, MACE and 1-year mortality in RCTs