Impact of distal embolization on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb–IIIa inhibitors: insights from the EGYPT cooperation

Even though primary angioplasty is able to obtain TIMI 3 flow in the vast majority of STEMI patients, epicardial recanalization does not guarantee optimal myocardial perfusion, that remain suboptimal in a relatively large proportion of patients. Large interest has been focused in recent years on the role of distal embolization as major determinant of impaired reperfusion. The aim of the current study was to investigate in a large cohort of STEMI undergoing primary angioplasty with Gp IIb–IIIa inhibitors the impact of distal embolization on myocardial perfusion and survival. Our population is represented by patients undergoing primary angioplasty for STEMI included in the EGYPT database. Distal embolization was defined as an abrupt ‘‘cutoff’’ in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak CK and CK-MB. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Data on distal embolization were available in a total of 1182 patients (71% of total population). Distal embolization was observed in 132 patients (11.1%). Patients with distal embolization were older (P < 0.001), with larger prevalence of diabetes (P = 0.01), previous MI (P = 0.048) and advanced Killip class at presentation (P = 0.018), abciximab administration (P < 0.001), with a lower prevalence of smoking (P = 0.04). Patients with distal embolization had more often poor preprocedural recanalization (P = 0.061), less often postprocedural TIMI 3 flow (P < 0.001), postprocedural MBG 2–3 (P < 0.001), complete ST-segment resolution (P = 0.021) and larger infarct size (CK-MB: 328 ± 356 U/l vs. 259 ± 226 U/l, P = 0.012). The impact of distal embolization on myocardial perfusion was confirmed after correction for baseline confounding factors as evaluated by MBG 2–3 (adjusted OR [95% CI] = 3.14 [2.06–4.77], P < 0.0001) but not complete ST-segment resolution (adjusted OR [95% CI] = 1.23 [0.84–1.92], P = 0.26). At 208 ± 160 days follow-up, distal embolization was associated with a significantly higher mortality (9.2% vs. 2.7%, HR [95% CI] = 3.41 [1.73–6.71], P < 0.0001), that was confirmed after correction for baseline confounding factors (adjusted HR [95% CI] = 2.23 [1.1–4.7], P = 0.026). This study showed among STEMI patients treated with Gp IIb–IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival.     

Gender-related differences in outcome after ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb–IIIa inhibitors: insights from the EGYPT cooperation

Several studies have found that among patients with ST-elevation myocardial infarction (STEMI) treated by thrombolysis, female sex is associated with a worse outcome. The aim of this study was to investigate sex-related differences in clinical and angiographic findings in patients with STEMI treated with primary angioplasty and Gp IIb–IIIa inhibitors. Our population is represented by 1662 patients undergoing primary angioplasty included in the EGYPT database. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Among 1662 patients, 379 were women (22.8%). Female sex was associated with more advanced age, higher prevalence of diabetes, hypertension, more advanced Killip class, longer ischemia time, less often smokers, with higher prevalence of preprocedural recenalization. No difference was observed in terms of postprocedural TIMI flow, myocardial perfusion and distal embolization. Similar findings were observed in terms of enzymatic infarct size and preprocedural ejection fraction. Female gender was associated with higher mortality (6.4% vs. 3.6%, HR = 1.83 [1.12–3.0], P = 0.015). However, the difference disappeared after correction for baseline confounding factors (HR = 1.01 [0.56–1.83], P = 0.98). This study shows that in patients with STEMI treated by primary angioplasty, female gender is associated with higher mortality rate in comparison with men, and this is mainly due to their higher clinical and angiographic risk profiles. In fact, female sex did not emerge as an independent predictor of mortality.     

Impact of diabetes on long-term outcome in STEMI patients undergoing primary angioplasty with glycoprotein IIb–IIIa inhibitors and BMS or DES

Diabetes has been shown to be associated with worse survival and repeat revascularization (TVR) after primary angioplasty. Drug-eluting stent (DES) may offer benefits in terms of TVR, that may be counterbalanced by an higher risk of stent thrombosis, especially among STEMI patients. Aim of the current study was to evaluate the impact of diabetes on 5-year outcome in patients undergoing primary angioplasty with Glycoprotein IIb–IIIa inhibitors in the era of DES. Our population is represented by STEMI patients undergoing primary angioplasty and stent implantation at a tertiary center with 24-h primary PCI capability within 12 h of symptom onset. All patients received glycoprotein IIb–IIIa inhibitors. No patient was lost to follow up. From 2003 to 2005, 270 STEMI patients were treated with DES (n = 180), or BMS (n = 90). A total of 69 patients had history of diabetes at admission (25.5%). At a follow-up of 1510 ± 406 days, diabetes was associated with a higher rate of death (29.5 vs. 5.1%, P < 0.0001), reinfarction (24.1 vs. 9.1%, P < 0.0001), TVR (19.1 vs. 13.1%, P = 0.052), IST (17.2 vs. 6.8%, P < 0.001) and MACE (51.9 vs. 25.1%, P < 0.001). These results were confirmed in both patients receiving BMS or DES, except for TVR, where no difference was observed between diabetic and non-diabetic patients. This study shows that among STEMI patients undergoing primary angioplasty with Gp IIb–IIIa inhibitors, diabetes is associated with worse long-term mortality, reinfarction, and IST, even with DES implantation, that, however, were able to equalize the outcome in terms of TVR as compared to non diabetic patients.     

Low-molecular-weight heparin compared with unfractionated heparin for patients with non–ST-segment elevation acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors: Results from the CRUSADE initiative

Background: Both heparin and glycoprotein (GP) IIb/IIIa inhibitor therapy and early invasive management strategies are recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the treatment of patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS). However, controversy exists about which form of heparin—unfractionated (UF) or low-molecular-weight (LMW)—is preferable. We sought to compare the efficacy and safety of these treatment strategies in a large contemporary population of patients with NSTE ACS. Methods: Using data from the CRUSADE Initiative, we evaluated LMWH and UFH in high-risk NSTE ACS patients (positive cardiac markers and/or ischemic ST-segment changes) who had received early (< 24 hours) GP IIb/IIIa inhibitor therapy and underwent early invasive management. In-hospital outcomes were compared among treatment groups. Results: From a total of 11,358 patients treated at 407 hospitals in the US from January 2002–June 2003, 6881 (60.6%) received UFH and 4477 (39.4%) received LMWH. Patients treated with UFH were more often admitted to a cardiology inpatient service (73.6% vs. 65.5%, P < 0.0001) and more frequently underwent diagnostic catheterization (91.8% vs. 85.9%, P < 0.0001) and percutaneous coronary intervention (PCI) (69.7% vs. 56.9%, P < 0.0001) than patients treated with LMWH. The point estimate of the adjusted risk of in-hospital death or reinfarction was slightly lower among patients treated with LMWH (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.67–0.99) and the risk of red blood cell transfusion was similar (OR 1.01, 95% CI 0.89–1.15). Among patients who underwent PCI within 48 hours, adjusted rates of death (OR 1.14, 95% CI 0.71–1.85), death or reinfarction (OR 0.93, 0.67–1.31), and transfusion (OR 1.16, 0.89–1.50) were similar. Patients who underwent PCI more than 48 hours into hospitalization had reduced rates of death (OR 0.64, 0.46–0.88), death or reinfarction (OR 0.57, 0.44–0.73), and transfusion (OR 0.66, 0.52–0.84). Conclusions: In routine clinical practice, patients treated with GP IIb/IIIa inhibitors have slightly improved outcomes and similar bleeding risks with LMWH than with UFH. These findings are consistent with current ACC/AHA guidelines but raise important questions about the safety and effectiveness of antithrombotic therapy in real-world clinical practice. Abbreviations abstract Using data from the CRUSADE Initiative, we evaluated low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in high-risk patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS) who received early (<24 hours) glycoprotein (GP) IIb/IIIa inhibitors and early invasive management. In-hospital outcomes were compared among treatment groups. LMWH was associated with slightly improved clinical outcomes and similar rates of transfusion compared with UFH. Our results support the current ACC/AHA guidelines recommendations but raise concerns about the safety and efficacy of UFH in the setting of background use of upstream GP IIb/IIIa inhibitors for patients with NSTE ACS in routine clinical practice. CRUSADE is funded by Millennium Pharmaceuticals, Inc. (Cambridge, Massachusetts) and Schering Corporation (Kenilworth, New Jersey). Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership provides an unrestricted grant in support of the program.     

Is it possible to simplify risk stratification scores for patients with ST-segment elevation myocardial infarction undergoing primary angioplasty?

IntroductionThere are several risk scores for stratification of patients with ST-segment elevation myocardial infarction (STEMI), the most widely used of which are the TIMI and GRACE scores. However, these are complex and require several variables. The aim of this study was to obtain a reduced model with fewer variables and similar predictive and discriminative ability.MethodsWe studied 607 patients (age 62 years, SD=13; 76% male) who were admitted with STEMI and underwent successful primary angioplasty. Our endpoints were all-cause in-hospital and 30-day mortality. Considering all variables from the TIMI and GRACE risk scores, multivariate logistic regression models were fitted to the data to identify the variables that best predicted death.ResultsCompared to the TIMI score, the GRACE score had better predictive and discriminative performance for in-hospital mortality, with similar results for 30-day mortality. After data modeling, the variables with highest predictive ability were age, serum creatinine, heart failure and the occurrence of cardiac arrest. The new predictive model was compared with the GRACE risk score, after internal validation using 10-fold cross validation. A similar discriminative performance was obtained and some improvement was achieved in estimates of probabilities of death (increased for patients who died and decreased for those who did not).ConclusionIt is possible to simplify risk stratification scores for STEMI and primary angioplasty using only four variables (age, serum creatinine, heart failure and cardiac arrest). This simplified model maintained a good predictive and discriminative performance for short-term mortality.     

Should primary angioplasty be available for all patients with an ST elevation myocardial infarction?

For the acute myocardial infarction patient, percutaneous coronary intervention is clearly superior to thrombolysis for many clinical end points, yet widespread availability of PCI services is still far from being realised.     

Angiographic perfusion score in patients treated with PCI at late angiography following fibrinolytic administration for ST-segment elevation myocardial infarction is associated with morbidity and mortality at 30 days

Background  Among patients with ST-segment elevation myocardial infarction (STEMI), evidence of restoration of both normal epicardial arterial flow and myocardial perfusion early after the administration of fibrinolytic agents has been associated with improved clinical outcomes. In STEMI patients treated with fibrinolytic therapy and scheduled for angiography later during hospital admission, however, the association of later indices of flow and perfusion with clinical outcomes has not been assessed. Methods  Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 enrolled 3,491 STEMI patients treated with fibrinolytic therapy. Angiography was scheduled 48–192 h (median 84) after randomization. The Angiographic Perfusion Score (APS) (the sum of the TIMI Flow Grade and Myocardial Perfusion Grade before and after percutaneous coronary intervention (PCI), range of 0–12) was assessed in the 1,460 patients treated with PCI at late angiography, and its association with morbidity and mortality at 30 days was examined. Results  Full perfusion, defined as an APS of 10–12, was associated with the lowest mortality (0.8%), while partial perfusion (APS 4–9) (2.3%) and failed perfusion (APS 0–3) (18.0%) were associated with a higher incidence of mortality at 30 days (P < 0.001 for full perfusion vs. partial perfusion, P < 0.0001 for overall trend). In addition, full perfusion was associated with a lower incidence of recurrent myocardial infarction (MI), a composite of death and MI, recurrent myocardial ischemia, ventricular tachyarrhythmia, congestive heart failure and shock (P < 0.05 for all trends). Conclusion  Among STEMI patients treated with late PCI following fibrinolytic therapy, higher APS is associated with reduced morbidity and mortality.     

Does glucose level at hospital discharge predict one-year mortality in patients with diabetes mellitus treated with percutaneous coronary intervention for ST-segment elevation myocardial infarction?

BACKGROUND: It has been shown that diabetes mellitus (DM) is an independent prognostic factor in patients with myocardial infarction (MI). In addition to that fact the prognostic significance of blood glucose (BG) abnormalities in the acute phase of MI has also been suggested. Recently, a new prognostic factor has been evaluated - the glucose level at hospital discharge. AIM: To assess whether the glucose level at hospital discharge is associated with one-year mortality in patients with DM treated with percutaneous coronary intervention (PCI) for ST-segment elevation MI (STEMI), taking into account hypoglycaemic treatment. METHODS: Consecutive patients with STEMI and DM treated with PCI, who survived hospitalisation, were included in the analysis. Patients were assumed to have DM if previous diagnosis of DM or newly diagnosed DM during hospital stay was noted. Criteria of newly diagnosed DM were as follows: fasting BG >or=7 mmol/l at least twice after acute phase of STEMI, BG >or=11.1 mmol/l in a 2-hour glucose tolerance test performed before discharge. Fasting plasma glucose at hospital discharge was used for analysis. RESULTS: Out of 2762 consecutive patients with STEMI, 565 had DM. In-hospital mortality in this group was 9.4% (53 patients), so the final DM group consisted of 512 patients. After discharge 59 (11.5%) patients died during one-year follow-up. The glucose level at discharge was not an independent prognostic factor of one-year mortality in the whole analysed group, however insulin treatment at discharge was (HR 2.61, 95% CI 1.29-5.29; p=0.008). Afterwards, we undertook multivariate analysis separately in the group treated with insulin (253 patients) and in the group treated with oral drugs or diet only (259 patients). This analysis showed that in the group treated with insulin the glucose level at discharge was not an independent prognostic factor of one-year mortality (HR 1.07, 95% CI 0.95-1.22; p=0.27), whereas in patients treated with hypoglycaemic agents or diet it was significantly associated with a one-year mortality (HR 1.30, 95% CI 1.01-1.68; p=0.049). CONCLUSIONS: 1. Patients with STEMI and DM treated with insulin at hospital discharge have higher risk of death, probably because of more advanced DM and more severe complications, than patients treated with oral drugs or diet. 2. Elevated glucose level at hospital discharge predict one-year mortality only in patients with MI and DM treated with oral drugs or diet.     

Impact of early abciximab administration on myocardial reperfusion in patients with ST-segment elevation myocardial infarction pretreated with 600 mg of clopidogrel before percutaneous coronary intervention

Early rapid platelet inhibition with abciximab before primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is suggested as beneficial. In previous studies on early abciximab administration clopidogrel was administered in cathlab in low loading dose. We investigated the role of early abciximab administration on top of early clopidogrel 600 mg loading dose in patients with STEMI treated with PPCI. A total of 73 non-shock STEMI < 6 h patients admitted to remote hospitals with anticipated delay to PPCI < 90 min were randomly assigned to three study groups—24 pts received abciximab before transfer to cathlab (early = group EA), 27 in cathlab during PPCI (late = group LA) and in 22 abciximab administration was left to operator’s discretion during PPCI (selective = SA; given in 22.7% of patients). All patients received clopidogrel (600 mg), aspirin and heparin (70 U/kg) before transfer to cathlab. Angiography revealed more frequent infarct-related artery patency (TIMI 2 + 3: EA vs LA vs SA: 45.8 vs 18.5 vs 13.6%, P = 0.024), better myocardial tissue perfusion (MBG 2 + 3: EA vs LA vs SA: 45.8 vs 14.8 vs 13.6%, P = 0.02) in EA group in baseline angiography. There was no difference in these angiographic parameters and ECG ST-segment resolution after PPCI. In multivariate analysis early abciximab administration was an independent predictor of infarct-related artery patency in baseline angiography (OR 6.5; 95% CI 1.83–23.1; P = 0.004). Early abciximab administration before transfer for PPCI in patients with STEMI pretreated with 600 mg of clopidogrel results in more frequent infarct-related artery patency and better myocardial tissue perfusion before PPCI.