Early infarct-related artery (IRA) patency is associated with better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Using the French Registry of ST-elevation and non–ST-elevation Myocardial Infarction (FAST-MI) 2010 registry, we investigated factors related to IRA patency (thrombolysis in myocardial infarction [TIMI] 2/3 flow) at the start of procedure in patients admitted for primary percutaneous coronary intervention. FAST-MI 2010 is a nationwide French registry including 4,169 patients with acute MI. Of 1,452 patients with STEMI with primary percutaneous coronary intervention, 466 (32%) had TIMI 2/3 flow of IRA before the procedure. Mean age (62 ± 14 years in both groups), Global Registry of Acute Coronary Event score (141 ± 31 vs 142 ± 34), and time from onset to angiography (472 ± 499 vs 451 ± 479 minutes) did not differ according to IRA patency (TIMI 2/3 vs TIMI 0/1). Using multivariate logistic regression analysis, IRA patency was more frequently found in patients having called earlier (time from onset to electrocardiogram [ECG] <120 minutes; odds ratio [OR] 1.49; 95% confidence interval [CI] 1.17 to 1.89), or receiving rapid-onset of action (prasugrel or glycoprotein IIb-IIIa) antiplatelet therapy in the prehospital setting (OR 1.59, 95% CI 1.14 to 2.21). Increasing time from diagnostic ECG to angiography was also associated with IRA patency (>90 minutes; OR 1.37, 95% CI 1.08 to 1.75). In conclusion, preprocedural IRA patency is observed in one third of patients with STEMI, it is more frequently found in patients having received fast-acting antiplatelet therapy before angiography, and in patients having called early. Higher IRA patency with increasing time delays from qualifying ECG to angiography suggests an additional role of spontaneous or medication-mediated fibrinolysis.
Early infarct-related artery (IRA) patency is associated with better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). However, limited data are available on factors related to IRA patency, and the role of pharmacologic agents is uncertain. Prehospital treatment of ongoing STEMI with fibrinolytic agents or glycoprotein IIb/IIIa inhibitors (GPIs) has been associated with improved coronary reperfusion and outcomes. However, there is limited information on pretreatment with clopidogrel in patients with STEMI who underwent percutaneous coronary intervention (PCI), but the available data suggest that there is no safety issue and that the rate of major cardiovascular events may be reduced. Recently, the Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST-Elevation Myocardial Infarction to Open the Coronary Artery (ATLANTIC) study, showed that the administration of the potent P2Y12-receptor antagonist ticagrelor shortly before PCI did not improve reperfusion of the culprit artery before the procedure but was safe and might prevent postprocedural acute stent thrombosis. The aim of the study was to investigate factors related to IRA patency at the start of procedure in patients admitted for primary PCI using data from the French registry of Acute ST-elevation or non–ST-elevation Myocardial Infarction (FAST-MI) 2010, with a specific focus on the potential relation with prehospital administration of antiplatelet agents.
Methods
FAST-MI 2010 is a national prospective multicenter registry including consecutive adult patients hospitalized for ST-elevation and non–ST-elevation acute MI (with symptom onset ≤48 hours) over a period of 1 month (from October 2010). Patients with acute MI after cardiovascular procedures were excluded. Participation in the study was offered to all intensive care units in French institutions (university teaching hospitals, general and regional hospitals, and private clinics) with the capacity to receive acute coronary syndrome emergencies. Details of the methods have been previously described. The main objective of this registry was to evaluate practices for MI management in routine practice and to measure their association with outcomes over a 10-year follow-up. The registry was conducted in compliance with Good Clinical Practice guidelines, French law, and the French data protection law. The protocol was reviewed and approved by the Committee for the Protection of Human Subjects of Saint-Louis University Hospital, and the data file of FAST-MI was declared to the Commission Nationale Informatique et Liberté ( Clinicaltrials.gov identifier: NCT01237418 ).
A total of 4,169 patients in 213 centers (76% of active centers in France) were included in this registry. Baseline characteristics were collected prospectively. All data were recorded on computerized case record forms by dedicated research technicians sent in each of the centers at least once a week. The research technicians were also asked to ensure that recruitment was consecutive. In the current analysis, we selected patients with STEMI who underwent emergency coronary angiography for intended primary PCI. STEMI was diagnosed when ST elevation ≥1 mm was seen in at least 2 contiguous leads in any location on the index or qualifying electrocardiogram (ECG) or when presumed new Q waves were observed. The degree of coronary flow before PCI was classified by thrombolysis in myocardial infarction (TIMI) grade flow as assessed by the investigators. Patients with TIMI grade 2 or 3 flow in the IRA were considered to have a patent vessel.
Statistical analysis was performed using the SPSS premium statistics 23.0 software (IBM Corporation). For quantitative variables, means and standard deviations were calculated. In addition, medians with interquartile ranges were calculated when appropriate. Discrete variables are presented as number of events and percentages. Comparisons were made with chi-square or Fisher’s exact tests for discrete variables, and by unpaired t tests, Mann–Whitney tests, or one-way analyses of variance for continuous variables. Correlates of IRA patency were determined using multivariate backward stepwise multiple logistic regression, including age, gender, time from onset to ECG, time from ECG to coronary angiography, main risk factors and co-morbidity, admission Killip’s class, heart rate, systolic blood pressure, medications used before the acute event, and prehospital antithrombotic therapy as covariables. To further analyze correlations between IRA patency and prehospital administration of antiplatelet agents, we calculated a propensity score for receiving antiplatelet agents with rapid onset of action (prasugrel and GPIs) in the prehospital setting, using a nonparsimonious binary logistic regression analysis also including time delays (c-statistic, 0.74). The propensity score was used as a single covariable together with actual prehospital treatment received, in a binary logistic regression analysis with IRA patency as the dependent variable. In addition, we used propensity score inverse probability weighting as a further method to assess the relation between prehospital use of rapid-onset antiplatelet agents and IRA patency. For all analyses, a p value <0.05 was considered significant.
Results
Of the 4,169 patients included in the registry, 2,364 had STEMI and were referred for intended primary PCI (n = 1,609) and had TIMI flow data available (n = 1,458). Thirty-two percent of patients had a TIMI 2/3 flow at the start of the procedure ( Table 1 ). Both groups (TIMI 0/1 or TIMI 2/3 flow) did not differ in many respects, in particular regarding the GRACE score; location of acute MI, history of MI, PCI or coronary artery bypass grafting, and co-morbidities. However, patients with TIMI flow 2/3 had a shorter time from symptom onset to qualifying ECG and a longer time from ECG to angiography ( Table 2 ). In addition, systolic blood pressure and heart rate were higher in these patients at initial clinical presentation; Killip’s class was similar in both groups. Prehospital treatment (i.e., anticoagulant and antiplatelet agents) was similar in both groups. Mortality at 30 days was significantly lower in patients with TIMI 2 or 3 flow compared with those with TIMI0 or 1 flow ( Supplementary Figure 1 ).
| Variable | TIMI flow 0/1 (n=990) | TIMI flow 2/3 (n=468) | P value |
|---|---|---|---|
| Age (years) | 61.6 ± 13.9 | 61.8 ± 13.8 | 0.74 |
| Women | 230 (23%) | 117 (25%) | 0.46 |
| Body mass index (kg/m 2 ) | 26.8 ± 4.5 | 26.6 ± 4.04 | 0.43 |
| Hypertension | 435 (44%) | 210 (45%) | 0.73 |
| Diabetes mellitus | 139(14%) | 66 (14%) | 0.97 |
| Current smoker | 449(45%) | 190 (41%) | 0.88 |
| Dyslipidemia ∗ | 375(38%) | 192 (41%) | 0.25 |
| Previous myocardial infarction | 97(10%) | 37(8%) | 0.24 |
| Previous percutaneous coronary intervention | 102(10%) | 35 (7.5%) | 0.08 |
| Previous coronary artery bypass grafting | 46(5%) | 24 (5%) | 0.69 |
| Previous heart failure | 15(1.5%) | 9 (2%) | 0.57 |
| Previous stroke | 33 (3%) | 17 (4%) | 0.77 |
| Peripheral artery disease | 47 (5%) | 16(3%) | 0.24 |
| Chronic renal failure | 19(2%) | 8 (2%) | 0.78 |
| GRACE score | 142 ± 33.5 | 140.9 ± 30.8 | 0.55 |
| Aspirin before admission | 530 (53.5%) | 256 (55%) | 0.68 |
| Clopidogrel before admission | 391(39.5%) | 183 (39%) | 0.45 |
| Beta-blockers before admission | 5 (0.5%) | 8 (2%) | 0.02 |
| Statins before admission | 3 (0.3%) | 1 (0.2%) | 0.76 |
| ACE-inhibitors or ARB before admission | 0 (0%) | 1 (0.2%) | 0.15 |
∗ Included patients with previously documented diagnosis of hypercholesterolemia be treated with diet or medication or new diagnosis made during this hospitalization with elevated total cholesterol >160 mg/dl, did not include elevated triglycerides.
| Variable | TIMI flow 0/1 (n=990) | TIMI flow 2/3 (n=468) | P value |
|---|---|---|---|
| Clinical présentation | |||
| Systolic blood pressure (mmHg) | 141 ± 28 | 145 ± 29 | 0.04 |
| Heart rate (beats/minute) | 76 ± 20 | 79 ± 20 | 0.07 |
| Anterior wall myocardial infarction | 407 (41%) | 210 (45%) | 0.17 |
| Killips Class | 0.44 | ||
| 1 | 850 (87%) | 409 (89%) | |
| 2 | 79 (8%) | 36 (8%) | |
| 3 | 21 (2%) | 10 (2%) | |
| 4 | 23 (2%) | 5 (1%) | |
| Left ventricle ejection fraction, mean ± SD | 50 ± 11 | 52 ± 11 | <0.001 |
| Time delays | |||
| Symptom onset to ECG (minutes) | 0.002 | ||
| Median [IQR] | 135 [70;322] | 110 [61;250] | |
| No. of patients | [n=940] | [n=433] | |
| Diagnostic ECG to angiography (minutes) | <0.001 | ||
| Median [IQR] | 93 [61;165] | 105 [71;207] | |
| No. of patients | [n=944] | [n=435] | |
| Pre-hospital medications | |||
| Low molecular weight heparin | 192 (19%) | 100 (21%) | 0.38 |
| Unfractionated heparin | 285 (29%) | 131 (28%) | 0.75 |
| Bivalirudin | 31 (3%) | 17 (4%) | 0.62 |
| Prasugrel | 97 (10%) | 60 (13%) | 0.08 |
| Clopidogrel | 391 (39.5%) | 183 (39%) | 0.89 |
| Glycoprotein IIb-IIIa inhibitors | 55 (9%) | 31 (13%) | 0.23 |
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