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Background: Systems-based strategies to improve STEMI care have traditionally focused on improving door to balloon time (D2BT) performance. However, prompt guideline-directed medical therapy (GDMT) and use of radial access for PCI are also associated with reduced mortality in patients with STEMI. The incremental value of each facet of STEMI care on mortality is unknown.Methods: On 7/15/14 we implemented a comprehensive four-step STEMI protocol at our institution: (1) ED physician cath lab activation (2) Safe STEMI Handoff Checklist with GDMT decision support (3) immediate transfer to an immediately available cath lab and (4) radial access for PCI. The protocol was intended to minimize care variability in GDMT (aspirin, P2Y12 inhibitor, and anticoagulant) prior to PCI, use of radial access for PCI, and D2BT. We studied consecutive patients with STEMI treated with PCI at our center (1/1/11-12/31/16) to assess the incremental prognostic value of these STEMI care processes using logistic regression models.Results: Of 1272 participants mean age was 61+/-12 years and 68% were men. STEMI presenting location was 25% primary ED, 69% inter-hospital transfer, and 6% in-hospital. The rates of GDMT prior to PCI (74% vs 83%, P<0.001) and radial access for PCI (19% vs. 67%, P<0.001) improved and median D2BT (106 [81-140] vs. 90 [68-109], P<0.001) decreased after implementation of the comprehensive four-step STEMI protocol. In a multivariable model, GDMT prior to PCI (OR 0.42, 95% CI 0.25-0.71, P=0.001), radial access for PCI (OR 0.44, 95% CI 0.23-0.82, P=0.002), and decreasing D2BT (10min decrease: OR 0.96, 95% CI 0.94-0.99, P=0.007) were each independently associated with reduced odds of in-hospital mortality. Step-wise modeling of the risk of in-hospital mortality demonstrated that GDMT prior to PCI, radial access for PCI, and D2BT performance provided incremental prognostic value when added in stepwise order of the occurrence of these care processes in clinical practice (Figure).Conclusions: Prompt GDMT administration, radial access for PCI, and D2BT performance add incremental prognostic value. Expanding STEMI systems of care from a singular focus on D2BT to a comprehensive focus on multi-faceted STEMI care offers an opportunity to further improve STEMI outcomes.