GRACE Score and Pre-Hospital Administration of Antiplatelet Medication in Estimating Mortality in Patients with Acute Coronary Syndrome

Acute coronary syndrome (ACS) is the acute manifestation of ischemic heart disease (IHD). In over 30% of IHD cases, the first symptom is sudden cardiac arrest (SCA), the majority of which progress into sudden cardiac death (SCD). ACS is associated with both short- and long-term mortality. The prognosis of an ACS patient is affected by numerous risk factors, such as comorbidities, individual cardiac manifestations, such as left ventricular ejection fraction (LVEF), and treatment decisions.

The patient’s prognosis and the severity of the myocardial infarction (MI) can be assessed with the global registry of acute myocardial events (GRACE) risk score, which is currently considered to be the gold standard for risk assessment in ACS. The effect of a patient’s comorbidities on the prognosis can be estimated with, for example, the Charlson Comorbidity Index (CCI) that estimates the 10-year survival based on the common comorbidities. The severity of the MI is associated with an increased risk of severe ventricular arrythmias after the MI, but current guidelines only assess patients’ risk of SCD based on the residual LVEF. It remains unknown whether the GRACE score could be utilized in estimating patients’ risk of SCA/SCD.

Adenosine diphosphate receptor (ADPr) blockers are the cornerstone of medical treatment in ACS and have drastically improved patient survival. ADPr blockers are typically administered before revascularization and daily until 12 months after the procedure. Newer ADPr blockers, ticagrelor and prasugrel, have been associated with a decreased risk of major adverse cardiac events and mortality compared to the older clopidogrel. However, the differences between the ADPr blockers in terms of a patient’s short-term prognosis and the outcome of coronary interventions in ACS remain unclear.

The goal of this thesis was to assess whether the prognostic performance of the GRACE score could be enhanced by the measurement of LVEF or recorded comorbidities at the time of ACS and to determine the applicability of the GRACE score in predicting SCA/SCD events after the ACS. It was also studied whether the choice of ADPr blocker was associated with short-term mortality and/or procedural success among ST-elevation myocardial infarction (STEMI) patients.

This thesis was an article dissertation comprising 4 substudies. Studies I–III were based on the retrospective MADDEC registry, whereas Study IV was a compilation of the MADDEC registry and data from the prospective MI-EKG study. The MADDEC registry comprises all patients treated in Tays Heart Hospital between 2007 and 2018 with applicable follow-up data on serious adverse events.
In Study I we studied whether the prognostic value of GRACE increases when complemented with a patient’s LVEF measured at the time of ACS. Both the GRACE and LVEF assessed at the point of admission were independently associated with 6-month mortality. GRACE predicted mortality well, and the risk discrimination increased significantly when it was complemented with LVEF.

In Study II the additive prognostic value of the CCI when added to GRACE was studied in ACS patients for different time frames (1, 6, 24 months) regarding overall survival. After adjusting with GRACE, the following CCI components were independently associated with mortality: diabetes and heart failure (all time frames), peripheral artery disease (6, 24 months), MI, chronic obstructive pulmonary disease, malignancy, and chronic kidney disease (24 months). GRACE predicted mortality significantly better than the CCI in all time frames. When complemented with the significant components of the CCI, the predictive value of GRACE did not increase significantly.

In Study III the association between prehospital administration of an ADPr blocker and short-term (3 and 7 days) mortality was studied among STEMI patients. The risk of mortality was lower in patients receiving ticagrelor or prasugrel compared to those receiving clopidogrel, but there was no statistically significant difference between the two newer drugs. Ticagrelor and prasugrel were also associated with an increased probability of moderate-to-good preprocedural blood flow into the culprit artery compared to clopidogrel. The favorable results of newer ADPr blockers were exceptionally potent among patients with a short treatment delay.

In Study IV the association between the patients’ GRACE scores and the long- term incidence of SCA and SCD was studied among MI patients. GRACE was associated with an increased risk of both SCA and SCD even after excluding the effect of age from the score and among patients without an indication for an implantable cardioverter-defibrillator.

The results of this thesis suggest that the predictive value of the GRACE score could be enhanced by complementing the score with LVEF and comorbidity data. The GRACE score was also significantly associated with the patients’ risk of an SCA after the MI. In addition, the selection of a prehospitally administered ADPr blocker was associated with both short-term mortality and pre-procedural culprit artery flow.