Several factors in addi- tion to patient activation of EMS contribute to delays, not all of which can be reconciled. Areas for continued research include prehospital EMS protocols, the approach to out-of-hospital car- diac arrest, triage and transfer algorithms, rapid availability of expert PCI services, and further refinement of the clinical and time-related factors that should prompt earlier use of fibrino- lytic therapy coupled with immediate transfer for PCI.129,633 635 The lack of correlation between shorter D2B times and reduced mortality should drive further efforts to improve all aspects of STEMI care.636 Regional systems should track, analyze, and report all STEMI and out-of-hospital cardiac arrest events as part of an ongoing process-improvement program. 12.3. Transfer and Management of Non High-Risk Patients After Administration of Fibrinolytic Therapy The indications for and timing of transfer for angiography with a view toward revascularization of non high-risk patients after successful fibrinolysis are still debated. Although there has been increasing activation of this pathway, the evidence base for its justification is still limited.358,360,365 12.4. Antithrombotic Therapy The optimum choice of P2Y12 receptor inhibitor and antico- agulant agents for patients with STEMI can be challenging. Individual genetic variability in drug absorption, metabolism, and effectiveness has been highlighted by the experience with clopidogrel in patients with ACS.285,637 The risks of bleeding also may vary across racial and ethnic groups.12 The roles of platelet function testing and genetic screening for clopidogrel metabolism in the acute phase of STEMI care are uncertain,289 especially with the availability of alternative P2Y12 receptor inhibitors. More information specific to patients with STEMI is needed with regard to the use of prasugrel, ticagrelor, novel factor Xa and IIa antagonists, and platelet protease activated The efficacy and safety of com- bination ( triple ) antithrombotic therapy must be addressed while less hazardous approaches are tested. 