A. W. J. van ’t Hof

Early glycoprotein IIb–IIIa inhibitors in primary angioplasty (EGYPT) cooperation: an individual patient data meta-analysis

Background: Even though time-to-treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits from early pharmacological reperfusion by glycoprotein (Gp) IIb–IIIa inhibitors are still unclear. The aim of this meta-analysis was to combine individual data from all randomised trials conducted on facilitated primary angioplasty by the use of early Gp IIb–IIIa inhibitors. Methods and results: The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. All randomised trials on facilitation by the early administration of Gp IIb–IIIa inhibitors in ST-segment elevation myocardial infarction (STEMI) were examined. No language restrictions were enforced. Individual patient data were obtained from 11 out of 13 trials, including 1662 patients (840 patients (50.5%) randomly assigned to early and 822 patients (49.5%) to late Gp IIb–IIIa inhibitor administration). Preprocedural Thrombolysis in Myocardial Infarction Study (TIMI) grade 3 flow was more frequent with early Gp IIb–IIIa inhibitors. Postprocedural TIMI 3 flow and myocardial blush grade 3 were higher with early Gp IIb–IIIa inhibitors but did not reach statistical significance except for abciximab, whereas the rate of complete ST-segment resolution was significantly higher with early Gp IIb–IIIa inhibitors. Mortality was not significantly different between groups, although early abciximab demonstrated improved survival compared with late administration, even after adjustment for clinical and angiographic confounding factors. Conclusions: This meta-analysis shows that pharmacological facilitation with the early administration of Gp IIb–IIIa inhibitors in patients undergoing primary angioplasty for STEMI is associated with significant benefits in terms of preprocedural epicardial recanalisation and ST-segment resolution, which translated into non-significant mortality benefits except for abciximab.

Tirofiban as adjunctive therapy for acute coronary syndromes and percutaneous coronary intervention: a meta-analysis of randomized trials

AIMS To perform a thorough and updated systematic review of randomized clinical trials comparing tirofiban vs. placebo or vs. abciximab. METHODS AND RESULTS We searched for randomized trials comparing tirofiban vs. placebo or any active control. Odds ratios (OR) were computed from individual studies and pooled with random-effect methods. Thirty-one studies were identified involving 20,006 patients (12 874 comparing tirofiban vs. heparin plus placebo or bivalirudin alone, and 7132 vs. abciximab). When compared with placebo, tirofiban was associated at 30 days with a significant reduction in mortality [OR = 0.68 (0.54-0.86); P = 0.001] and death or myocardial infarction (MI) [OR = 0.69 (0.58-0.81); P < 0.001]. The treatment benefit persisted at follow-up but came at an increased risk of minor bleedings [OR = 1.42 (1.13, 1.79), P = 0.002] or thrombocytopenia. When compared with abciximab, mortality at 30 days did not differ [OR = 0.90 (0.53, 1.54); P = 0.70], but in the overall group tirofiban trended to increase the composite of death or MI [OR = 1.18 (0.96, 1.45); P = 0.11]. No such trend persisted at medium-term follow-up or when appraising studies testing tirofiban at 25 microg/kg bolus regimen. CONCLUSION Tirofiban administration reduces mortality, the composite of death or MI and increases minor bleedings when compared with placebo. An early ischaemic hazard disfavouring tirofiban was noted when compared with abciximab in studies based on 10 but not 25 microg/kg tirofiban bolus regimen.

Is routine stenting for acute myocardial infarction superior to balloon angioplasty? A randomised comparison in a large cohort of unselected patients

Objective: To evaluate the impact of routine stenting, compared with balloon angioplasty, in unselected patients presenting with ST segment elevation myocardial infarction (STEMI). Design: Randomised trial. Setting: Tertiary referral centre. Participants: All patients presenting with STEMI randomly assigned to stenting or balloon angioplasty. No exclusion criteria were applied. Main outcome measure: The primary end point was combined death or reinfarction at one year’s follow up. Results: 1683 consecutive patients with STEMI were randomly assigned before angiography to stenting (n  =  849) or balloon angioplasty (n  =  834). A total of 785 patients (92.5%) in the stent group and 763 patients (91.5%) in the balloon group actually underwent primary angioplasty. The groups were comparable in terms of postprocedural TIMI (thrombolysis in myocardial infarction) flow, myocardial blush grade, and distal embolisation. No difference was observed in clinical outcome at both intention to treat (14% v 12.5%, not significant) and actual treatment analyses (12.4% v 11.3%, not significant). Conclusions: Compared with balloon angioplasty, routine stenting does not seem to reduce death and reinfarction in a large cohort of unselected patients with STEMI.

Primary percutaneous coronary intervention versus thrombolytic treatment: long term follow up according to infarct location

Objectives: To study the clinical significance of infarct location during long term follow up in a trial comparing thrombolysis with primary angioplasty. Design: Retrospective longitudinal cohort analysis of prospectively entered data. Setting: Patients with acute ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Patients: In the Zwolle trial 395 patients with acute STEMI were randomly assigned to intravenous streptokinase or PCI. Main outcome measures: Survival according to infarct location and treatment after 8 (2) years of follow up. Results: 105 patients died: 63 patients in the streptokinase group and 42 patients in the primary PCI group (relative risk (RR) 1.6, 95% confidence interval (CI) 1.0 to 2.6; p  =  0.03). In patients with non-anterior STEMI there was no difference in mortality between streptokinase and PCI treated patients (RR 1.1, 95% CI 0.6 to 2.1; p  =  0.68) but the streptokinase group had significantly more major adverse cardiac events (MACE) than the PCI group (RR 2.1, 95% CI 1.2 to 3.6). The number needed to treat to prevent one MACE was four. In patients with anterior STEMI, mortality was higher in the streptokinase group than in the PCI group (RR 2.7, 95% CI 1.4 to 5.5; p  =  0.004). The number needed to treat to prevent one death was five. Kaplan-Meier analysis confirmed the benefits of primary angioplasty in the first year and showed additional benefit of PCI compared with streptokinase between 1–8 years after the acute event. Conclusions: Patients with anterior STEMI have better long term survival when treated with PCI than with streptokinase. In patients alive one year after the acute event, PCI confers a significant additional survival benefit, probably due to better preserved residual left ventricular function.

Non-culprit lesions detected during primary PCI: treat invasively or follow the guidelines?

AIMS: Evidence regarding the optimal treatment of non-culprit lesions detected during primary PCI is lacking. Our aim was to investigate whether early invasive treatment improves left ventricular ejection fraction (EF) and prevents major adverse cardiac events (MACE). METHODS AND RESULTS: Of 121 patients with at least one non-culprit lesion, 80 were randomised to early FFRguided PCI (invasive group), and 41 to medical treatment (conservative group). Primary endpoint was EF at six months, secondary endpoints included MACE. In the invasive group, early angiography was performed 7.5 days (5-20) after primary PCI. Forty percent of the non-culprit lesions did not show haemodynamic significance (FFR > 0.75). Subsequent PCI of at least one non-culprit lesion was performed in 52%, PCI without preceding FFR was performed in 8% and elective CABG was done in 4%. No in-hospital events occurred in the conservative group. After six months, EF was comparable (59+/-9% vs. 57+/-9%, p=0.362), and there was no difference in MACE between invasively and conservatively treated patients (21 vs. 22%, p=0.929). CONCLUSIONS: An invasive strategy towards non-culprit lesions does not lead to an increase in EF or a reduction in MACE. The functional stenosis severity of non-culprit lesions is frequently overestimated.

P2Y12 receptor inhibition and effect of morphine in patients undergoing primary PCI for ST-segment elevation myocardial infarction. The PRIVATE-ATLANTIC study.

PRIVATE-ATLANTIC (P2Y12 Receptor Inhibition with VASP Testing using Elisa kit during the ATLANTIC study) is a pre-specified substudy of the randomised, double-blind ATLANTIC trial in patients with ST-segment elevation myocardial infarction, designed to help interpret the main trial results. The primary objective of ATLANTIC was to assess coronary reperfusion prior to percutaneous coronary intervention (PCI) with pre- vs in-hospital ticagrelor 180 mg loading dose (LD). PRIVATE-ATLANTIC assessed platelet inhibition in 37 patients by measurement of vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) and VerifyNow platelet reactivity units (PRU) before angiogram (T1), immediately after PCI (T2), 1 (T3), and 6 (T4) hours (h) after PCI, and before next study drug administration (T5). The median time difference between the two ticagrelor LD was 41 minutes. Platelet reactivity was unaffected at T1 when measured by VASP-PRI (89.8 vs 93.9 % for pre- and in-hospital ticagrelor, respectively; p = 0.18) or PRU (239 vs 241; p = 0.82). Numerical differences were apparent at T2 and maximal at T3. Morphine administration significantly delayed onset of platelet inhibition at T3 (VASP-PRI 78.2 vs 23.4 % without morphine; p = 0.0116) and T4 (33.1 vs 11.0 %; p = 0.0057). In conclusion, platelet inhibition in ATLANTIC was unaffected by pre-hospital ticagrelor administration at the time of initial angiogram due to the short transfer delay. The maximum difference in platelet inhibition was detected 1 h after PCI (T3). Morphine administration was associated with delayed onset of action of ticagrelor and appeared more important than timing of ticagrelor administration.

Circumflex artery-related acute myocardial infarction : limited ECG abnormalities but poor outcome

Background. Circumflex (CX) artery-related myocardial infarction (MI) is less well represented in trials on ST-elevation acute myocardial infarction (STEMI), most often due to the absence of significant ST-segment elevation, and therefore the outcome of these patients is less well known. We aimed to compare the outcome of patients with CX versus right coronary artery (RCA) related STEMI in a large cohort of patients treated with primary angioplasty.Methods. A total of 1683 consecutive patients with STEMI were studied. Patients who lacked STsegment elevation were also included if they had persistent chest pain with signs of ischaemia or regional wall motion abnormalities on echocardiography. Coronary angioplasty was performed according to standard procedures. After the intervention, all patients received aspirin and clopidogrel or ticlopidine.Results. The infarct-related vessel was the CX in 229 patients (14%) and the RCA in 600 patients (36%). No differences in baseline characteristics were present. Mean extent of ST-segment elevation or deviation was significantly higher in patients with the RCA as infarct-related vessel. Enzymatic infarct size was significantly higher in the CXrelated MI (1338±1117 IU/l vs. 1806±1498 IU/l, p<0.001). Left ventricular ejection fraction <45% was more often present in patients with CXrelated MI (37 vs. 26%, p<0.01). Both short- and long-term mortality were significantly higher in the CX-related MI.Conclusion. This study emphasises the fact that CX-related infarction has a worse prognosis compared with RCA-related infarction. (Neth Heart J 2007;15:286-90.)

Incidence, predictors and prognostic importance of bleeding after primary PCI for ST-elevation myocardial infarction

AIMS: To investigate incidence, predictors and prognosis of bleeding in ST elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: A large scale, prospective, observational study was performed between 1991 and 2004 in a single teaching hospital in The Netherlands including all consecutive STEMI patients who underwent primary PCI. The independent association between both major and minor bleeding and one year mortality was evaluated using Cox proportional hazard models. A total of 5,030 patients were included, of whom 109 patients (2%) had cardiac surgery within 48 hours. Data on bleeding or = 2 on admission, anterior MI location and TIMI 0 flow before PCI. Killip class > or = 2 on admission was an independent predictor of major bleeding. Major bleeding (HR 3.5 [95% CI 2.3-5.4]) was associated with an increased risk of death at one year. CONCLUSIONS: After primary PCI, the incidence of major bleeding is less than 2%. Although relatively infrequent, major bleeding complications are strongly and independently related to short- and midterm mortality.

Postprocedural single-lead ST-segment deviation and long-term mortality in patients with ST-segment elevation myocardial infarction treated by primary angioplasty

Objective: To evaluate the prognostic role of postprocedural single-lead residual ST-segment deviation for electrocardiographic evaluation of myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary angioplasty. Design: Prospective observational clinical cohort study. Setting: Tertiary referral centre. Patients: 1660 patients treated with primary angioplasty for STEMI. Main outcome measure: Mortality at 1-year follow-up. Results: Single-lead ST-segment deviation significantly correlated with infarct size, predischarge ejection fraction, distal embolisation and myocardial blush grade 3. At 1-year follow-up, 63 patients had died. The method correlated well with 1-year mortality. At multivariate analysis, after correction for baseline demographic, clinical and angiographic variables, postprocedural single-lead ST-segment deviation showed better accuracy than residual single-lead ST-segment elevation or resolution and residual 12-lead ST-segment deviation. Conclusions: This study showed that maximal residual ST-segment deviation in a single lead at 3 hours after the procedure is an easy and accurate predictor of 1-year mortality after primary angioplasty for STEMI.

Therapeutic mild hypothermia improves outcome after out-of-hospital cardiac arrest

Purpose. Therapeutic mild hypothermia (TMH) is indicated for comatose survivors of an out-ofhospital cardiac arrest (OHCA) to improve general outcome. Although widely used, there are not many reports on its use on a critical care unit (CCU) or on the comparison of cooling methods.Methods. In a retrospective analysis covering January 2005 to December 2006, 75 consecutive comatose subjects post-OHCA due to ventricular fibrillation and nonventricular fibrillation rhythms (asystole/pulseless electrical activity) were studied in a single tertiary PCI centre. Subjects treated with conventional post-resuscitation care without TMH served as controls (n=26; Jan 2005–Sep 2005). Outcome from controls at hospital discharge was compared with subjects treated with TMH (n=49; Oct 2005–Dec 2006). During the study period, TMH was induced by either external (n=25; Oct 2005–Feb 2006) or endovascular (n=24; Mar 2006–Dec 2006) approach.Results. Besides more females in the control group, there were no major differences in baseline characteristics present between all groups. TMH improved survival (OR 0.36 [0.13–0.95], p<0.05) and neurological outcome (OR 0.23 [0.07–0.70], p<0.01). After subanalysis, TMH-improved outcome did not differ between the two cooling methods used. However, the times to reach TMH and normothermia were shorter with the endovascular approach.Conclusion. TMH induced on a CCU improves survival and neurological outcome after post-OHCA coma. TMH by endovascular approach was more feasible compared with external cooling, but the two cooling methods did not result in a different outcome. (Neth Heart J 2009;17:378–84.)