Predictors of Survival After Contemporary Percutaneous Coronary Revascularization for Acute Myocardial Infarction in the Real Wo

Management strategies for ST-elevation myocardial infarction (STEMI) have undergone great evolution over the past decade. Currently, primary mechanical reperfusion is considered superior to thrombolytic therapy in achieving complete and sustained reperfusion of the infarct-related coronary artery, resulting in lower rate of mortality and re-infarction.^1–3 In many developed countries, patients presenting with STEMI are often directly transferred to the cardiac catheterization laboratory for mechanical reperfusion. In parallel to this approach, there have been tremendous advents in the equipment, medication and strategies employed in the catheterization laboratory. Plain balloon angioplasty was once the recommended treatment for STEMI, due to the risk of thrombosis after stent implantation. However, this has changed since the adoption of dual anti-platelet therapy after high-pressure stent deployment producing a thrombosis rate of about 1%.⁴ Nowadays, thienopyridine-derivative ticlopidine or clopidogrel are standard anti-platelet agents given together with aspirin after stent implantation. Intravenous platelet glycoprotein (GP) IIb/IIIa inhibitors have been shown to improve outcomes in patients undergoing percutaneous coronary intervention (PCI) for unstable angina and non-ST elevation MI.5,6 Their role in mechanical reperfusion for STEMI is being investigated.^7,8 The objectives of this study were to evaluate the in-hospital and long-term clinical outcomes, as well as the predictors of survival among patients who were treated with the most contemporary percutaneous coronary revascularization strategies for STEMI in real clinical practice. Patients and Methods Study design. This is a retrospective study of the in-hospital and long-term clinical outcomes in a tertiary university hospital (Thoraxcenter, Rotterdam). All patients who underwent primary PCI for STEMI in our institution during the period from October 1, 2000 to April 30, 2002 formed the study cohort. Diagnosis of STEMI was based on chest pain suggestive of coronary ischemia for more than 30 minutes and an ECG showing ST-segment elevation > 1 mm in 2 contiguous leads or new onset left bundle branch block, with or without cardiac enzyme elevation. All patients underwent PCI within 12 hours after onset of chest pain and none of them had received prior thrombolytic therapy. Submission for PCI was based on the decision of the attending physicians. As per hospital protocol, patients found to have significant left main coronary stenosis by angiography were discussed with the cardiothoracic surgeons for emergency bypass surgery. Only if declined by the surgeons would adhoc mechanical reperfusion in the catheterization laboratory be performed. Procedure. The PCI procedures were carried out in a standard fashion in the cardiac catheterization laboratory. Oral informed consents were obtained from all patients. All patients received combined aspirin and ticlopidine/clopidogrel loading dose prior to procedure. Weight-adjusted (100 U/kg) heparin with target activated clotting time (ACT) of > 300 seconds was administered before balloon inflation or stent deployment. When a platelet GP IIb/IIIa inhibitor had been given, reduced-dose (70 U/kg) heparin was administered with target ACT between 200 and 250 seconds. Details of the procedural strategy including direct stenting versus balloon predilatation, use of intra-aortic balloon pump (IABP) or other adjunctive devices were left to the discretion of the individual operator. Baseline and final TIMI flow of the infarct-related artery were determined by individual operator and recorded prospectively. A closure device was used to seal the femoral puncture sites after the procedure. After stent implantation, dual anti-platelet therapy with aspirin indefinitely and clopidogrel 75 mg daily for 4 weeks were given. Data collection. The patient in-hospital records, catheterization reports and discharge summaries were reviewed retrospectively in order to obtain information on patients’ demographics, presenting clinical history, procedural detail and in-hospital outcomes. Angiographic films were reviewed when relevant information was missing or inadequate. Hypercholesterolemia was defined as total cholesterol > 220 mg/dl. Hypertension was defined as systolic blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mmHg. Diabetes mellitus was defined as fasting blood sugar > 140 mg/dl. Multi-vessel disease was defined as > 50% stenosis in either 2 or all 3 major epicardial coronary arteries. Left ventricular ejection fraction was assessed by either, or both, left ventriculography and transthoracic echocardiography, and categorized into 3 groups: good (> 50%), moderate (30–50%) and poor (Statistics. Continuous data are expressed as mean value + standard deviation (SD) and were compared using Student’s t-test, categorical variable by chi-square tests. Cumulative survival curves were constructed using the Kaplan-Meier method. Amongst patient subgroups the log-rank test was used to compare survival curves. A stepwise, multivariable Cox analysis was carried out with the use of baseline clinical and angiographic characteristics and procedure-related variables (including the method of revascularization) in order to identify independent predictors of 2-year survival and event-free-survival. Statistical significance was defined as a p value Patient characteristics. A total of 316 patients underwent primary PCI for STEMI during the study period. The patients’ demographic data are listed in Table 1, and the angiographic findings are summarized in Table 2. The average age of the patients was 57.9 + 12.4 years. The majority (78%) were male. Around half (44.7%) the patients sustained an anterior STEMI and 58% of patients had a culprit lesion in the left anterior descending (LAD) artery. Only rarely was the left main coronary artery (1.2%) or vein graft (0.4%) the culprit vessel. This is probably because most patients who were found to have left main lesion were diverted to CABG, which is still the recommended treatment. Multi-vessel disease was present in 51.6% of the patients. Left ventricular function was impaired in 47.7% of the patients. Cardiogenic shock was present in 21.9% and resuscitated cardiac arrest due to ventricular tachycardia/fibrillation had occurred in 11.7% of the patients before the procedure. Procedural outcomes. Details of the procedures are shown in Table 3. At baseline, 76% of patients had TIMI 0–1 flow. The overall angiographic success rate, defined as residual stenosis of In-hospital and 30-day outcomes. Clinical outcomes are summarized in Table 4. The in-hospital mortality rate was 11.1%. The incidence of in-hospital MACE was 20%. The 30-day mortality rate was 13.9%. The incidence of 30-day MACE was 26%. Factors significantly associated with higher mortality by multivariable analysis are listed in Table 5. Multivariable analysis showed that age > 65 (Hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.04–1.13, p Long-term outcomes. Among the 316 patients, 314 (99.4%) had complete follow-up data. The average follow-up period was 1.2 years (range 5 months-2.00 years). The overall survival rate was 78.2%. Figure 1 shows the survival curves during the observation period in a Kaplan-Meier analysis. Factors associated with higher long-term mortality were the same as those that predicted 30-day mortality, including age > 65 (HR 1.09, 95% CI 1.04–1.10, p GP IIb/IIIa Inhibitor. Fifty-one percent of the patients were treated with intravenous GP IIb/IIIa inhibitors during the procedure. Among these patients, most (95%) received abciximab and the remaining received eptifibatide. The patients who received GP IIb/IIIa inhibitors were in general younger, had a higher prevalence of adverse cardiac risk factors and higher incidence of no-reflow and residual thrombus (data not shown). Four patients (3%) developed major bleeding episodes attributable to the drugs, including hematuria (n = 2), gastrointestinal bleeding (n = 2) and intracranial hemorrhage (n = 1). Overall angiographic success (98.8% versus 96.1%, p = NS), survival (86.2% versus 82.5%, p = NS) and event-free survival (68.3% versus 63.3%, p = NS) were similar among the patients with, versus those without GP IIb/IIIa inhibitors. Discussion In the present study, patients treated with contemporary percutaneous revascularization strategy in real clinical practice had worse clinical profiles than those enrolled in randomized trials, and this was associated with a higher incidence of in-hospital and long-term adverse outcomes. Survival was predicted by young age, absence of cardiogenic shock, resuscitated cardiac arrest and intubation during the procedure. Among patients with cardiogenic shock, different locations of infarction have no significant impact on survival. Although published prospective, randomized trials on PCI for STEMI have elegant study design and statistical analysis, generalizability of the results to real clinical practice is often doubtful. Most of these studies only focused on certain issues and excluded patients with important but unfavorable clinical parameters. Furthermore, some only presented the outcomes at 6 months. The clinical and procedural characteristics of our cohort have major differences from other studies. There was a high incidence of cardiogenic shock (21.9%) and resuscitated cardiac arrest (11.7%) in our study. The development of cardiogenic shock and cardiac arrest in a patient following STEMI heralds a dismal prognosis. For instance, the 7.2% of patients developing cardiogenic shock in the GUSTO-1 trial accounted for 58% of the overall deaths at 30 days.9 Most previous studies either excluded patients with these features.2,8,10,11 or the incidence was not reported.12 Likewise, in 2 recent studies on outcomes after PCI for STEMI in unselected patients,13,14 stent implantation occurred in 38% and 89% only of the patients and GP IIb/IIIa inhibitor was not used in both studies. In contrast, stent implantation was performed in 96.2% and GP IIb/IIIa inhibitor was given in 51% of our patient population. Taken together, our study reflects real clinical experience of coronary intervention using the most contemporary strategy. The observed 30-day mortality rates (13.9%) are higher than that reported in previous randomized trials which ranged from 2.2% to 6.6%.7,8,10 Instead, our findings were more close to that reported in studies that represent a “real world” clinical practice in unselected patients,15–17 or those of high-risk patients after STEMI.18 The most obvious reason for the observed high mortality was the high incidence of cardiogenic shock, resuscitated cardiac arrest and intubation prior to the procedure, which reflects the overall unfavorable clinical profiles of our patients. When patients with cardiogenic shock were excluded, the 30-day mortality (5.5%) was in fact similar to the reported in randomized trials. On the other hand, when considering only those patients who were in cardiogenic shock, the 30-day mortality rate (24.2%) was also not significantly different from that (38%) reported in the shock patients underwent aggressive revascularization in the GUSTO-I trial.19 The long-term mortality rate was 21.8%, which is also significantly higher than the value reported by others. Once again this can be attributed to the unfavorable patient profiles. In addition, the same factors predicting short-term mortality (age > 65, cardiogenic shock, resuscitated cardiac arrest and intubation) were found predictive of long-term mortality. In the present study, the estimated 2-year survival in patients with cardiogenic shock was significantly lower than those without shock (60% versus 92.2%). Besides, a previous study found that patients resuscitated from cardiac arrest had an in-hospital mortality rate of 32%.12 In agreement with this, the survival rate amongst our patients with resuscitated cardiac arrest was significantly lower than the rest (44% versus 84%). Around one third (32.7%) of the patients have experienced one or more MACE during the study period. Only multi-vessel disease was found predictive of occurrence of MACE. Cardiogenic shock has been well described as a predictor of mortality in STEMI. Algorithms using easily available clinical variable have been devised to predict the occurrence of in-hospital cardiogenic shock among patients with STEMI.20 In the GISSI-I study, patients with cardiogenic shock who were treated with streptokinase was associated with a 21 days mortality of 69.9%, which was not different from that treated by placebo (70.1%).21 On the other hand, aggressive mechanical revascularization has been shown to improve survival among patients with cardiogenic shock in the GUSTO-I and SHOCK trials, with survival benefit persisted after 12 months of follow-up.9,22 Although there have been reports showing that inferior MI with RV involvement is associated with higher mortality than those without RV involvement, these are mainly due to higher incidence of cardiogenic shock in the former group. The present study provides insight into the prognostic significance of different MI locations among patients with cardiogenic shock. Our results suggest that there is no significant difference in survival for cardiogenic shock due to anterior MI or inferior MI with/without RV involvement, which is in agreement with a recent report. However, this finding must be interpreted with caution due to small number of patients in each subgroup. Intravenous platelet GP IIb/IIIa inhibitors have been proven effective in reducing adverse events in unstable angina and non-ST elevation MI, especially for those submitted to early coronary intervention. In patients who were treated with stent implantation for STEMI, intravenous abciximab has been shown to improve microvascular perfusion and myocardial contractile function.25 On the other hand, in 2 recent prospective studies on clinical outcomes, conflicting results were obtained.7,8 Among our study patients, those who received GP IIb/IIIa inhibitors were younger and had higher prevalence of cardiovascular risk factors. The observed higher incidence of no-reflow and residual thrombus in patients who received GP IIb/IIIa inhibitor is likely due to the fact that this medication is often administered as a rescue measure for these conditions. In our cohort, survival was the similar between those who did or did not receive GP IIb/IIIa inhibitors. However, due to the higher risk profile of the patients given the medication, genuine benefit cannot be excluded and further randomized trials are warranted. Limitations. This was a retrospective study. Although under the hospital policy, all patients underwent the PCI procedure within 12 hours after onset of chest pain, the exact symptom to balloon time was not determined. In addition, we do not have detailed information on medication use after the procedure. Planned versus rescue use of GP IIb/IIIa inhibitors was not determined. Some patients were transferred back to the original hospital after the procedure and the their duration of hospital stay was not determined. Conclusion. In our cohort of patients who underwent contemporary PCI in real clinical practice, there was higher incidence of adverse event than reported in randomized studies. This is likely due to higher prevalence of adverse clinical profiles. Age > 65, cardiogenic shock, resuscitated cardiac arrest and intubation independently predicted in-hospital and long-term mortality, whilst multi-vessel disease predicted MACE. Among patients with cardiogenic shock, no significant survival differences were observed among patients with different sites of MI.

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