Arnoud W.J. van 't Hof

Angiographic Assessment of Myocardial Reperfusion in Patients Treated With Primary Angioplasty for Acute Myocardial Infarction Myocardial Blush Grade

BACKGROUND The primary objective of reperfusion therapies for acute myocardial infarction is not only restoration of blood flow in the epicardial coronary artery but also complete and sustained reperfusion of the infarcted part of the myocardium. METHODS AND RESULTS We studied 777 patients who underwent primary coronary angioplasty during a 6-year period and investigated the value of angiographic evidence of myocardial reperfusion (myocardial blush grade) in relation to the extent of ST-segment elevation resolution, enzymatic infarct size, left ventricular function, and long-term mortality. The myocardial blush immediately after the angioplasty procedure was graded by two experienced investigators, who were otherwise blinded to all clinical data: 0, no myocardial blush; 1, minimal myocardial blush; 2, moderate myocardial blush; and 3, normal myocardial blush. The myocardial blush was related to the extent of the early ST-segment elevation resolution on the 12-lead ECG. Patients with blush grades 3, 2, and 0/1 had enzymatic infarct sizes of 757, 1143, and 1623 (P<0.0001), respectively, and ejection fractions of 50%, 46%, and 39%, respectively (P<0.0001). After a mean+/-SD follow-up of 1.9+/-1.7 years, mortality rates of patients with myocardial blush grades 3, 2, and 0/1 were 3%, 6%, and 23% (P<0.0001), respectively. Multivariate analysis showed that the myocardial blush grade was a predictor of long-term mortality, independent of Killip class, Thrombolysis In Myocardial Infarction grade flow, left ventricular ejection fraction (LVEF), and other clinical variables. CONCLUSIONS In patients after reperfusion therapy, the myocardial blush grade as seen on the coronary angiogram can be used to describe the effectiveness of myocardial reperfusion and is an independent predictor of long-term mortality.

Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial

BACKGROUND If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with clopidogrel plus aspirin. METHODS We did an open-label, multicentre, randomised, controlled trial in 15 centres in Belgium and the Netherlands. From November, 2008, to November, 2011, adults receiving oral anticoagulants and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769938. FINDINGS 573 patients were enrolled and 1-year data were available for 279 (98·2%) patients assigned double therapy and 284 (98·3%) assigned triple therapy. Mean ages were 70·3 (SD 7·0) years and 69·5 (8·0) years, respectively. Bleeding episodes were seen in 54 (19·4%) patients receiving double therapy and in 126 (44·4%) receiving triple therapy (hazard ratio [HR] 0·36, 95% CI 0·26-0·50, p<0·0001). In the double-therapy group, six (2·2%) patients had multiple bleeding events, compared with 34 (12·0%) in the triple-therapy group. 11 (3·9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9·5%) patients in the triple-therapy group (odds ratio from Kaplan-Meier curve 0·39, 95% CI 0·17-0·84, p=0·011). INTERPRETATION Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events. FUNDING Antonius Ziekenhuis Foundation, Strect Foundation.

Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction

BACKGROUND A simple clinical method to stratify risk for patients who have had successful reperfusion therapy after myocardial infarction is attractive since it facilitates the tailoring of therapy. METHODS We investigated the clinical value of the 12-lead electrocardiogram (ECG), in 403 patients after successful reperfusion therapy by primary coronary angioplasty, in relation to infarct size measured by enzyme activity, left-ventricular function, and clinical outcome. ECGs were analysed to find the extent of the ST-segment-elevation resolution 1 h after reperfusion therapy. FINDINGS A normalised ST segment was seen in 51% of patients, a partly normalised ST segment in 34%, and 15% had no ST-segment-elevation resolution. Enzymatic infarct size and ejection fraction were related to the extent of the early resolution of the ST segment. The relative risk of death among patients with no resolution compared with patients with a normalised ST segment was 8.7 (95% CI 3.7-20.1), and that among patients with partial resolution compared with patients with a normalised ST segment was 3.6 (1.6-8.3). INTERPRETATION Our findings suggest that ECG patterns reflect the effectiveness of myocardial reperfusion. Patients for whom reperfusion therapy by primary angioplasty was successful and who had normalised ST segments had limited damage to the myocardium and an excellent outlook during follow-up. Patients with persistent ST elevation after reperfusion therapy may need additional interventions since they have more extensive myocardial damage and have a higher mortality rate.

Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.

BACKGROUND The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre. METHODS We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297. FINDINGS 936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36). INTERPRETATION Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.

Randomized Comparison of Coronary Stenting With Balloon Angioplasty in Selected Patients With Acute Myocardial Infarction

BACKGROUND Although the benefits of primary angioplasty in acute myocardial infarction have been demonstrated, several areas for improvement remain. Therefore, a prospective randomized trial comparing primary stenting with balloon angioplasty in patients with acute myocardial infarction was conducted. METHODS AND RESULTS Patients with acute myocardial infarction were randomly assigned to undergo either primary stenting (n=112) or balloon angioplasty (n=115). The clinical end points were death, recurrent infarction, subsequent bypass surgery, or repeat angioplasty of the infarct-related vessel. The overall mortality rate at 6 months was 2%. Recurrent infarction occurred in 8 patients (7%) after balloon angioplasty and in 1 (1%) after stenting (P=0.036). Subsequent target-vessel revascularization was necessary in 19 (17%) and 4 (4%) patients, respectively (P=0.0016). The cardiac event-free survival rate in the stent group was significantly higher than in the balloon angioplasty group (95% versus 80%; P=0.012). CONCLUSIONS In selected patients with acute myocardial infarction, primary stenting can be applied safely and effectively, resulting in a lower incidence of recurrent infarction and a significant reduction in the need for subsequent target-vessel revascularization compared with balloon angioplasty.

Angiographic Assessment of Reperfusion in Acute Myocardial Infarction by Myocardial Blush Grade

Background—Angiographic successful reperfusion in acute myocardial infarction has been defined as TIMI 3 flow. However, TIMI 3 flow does not always result in effective myocardial reperfusion. Myocardial blush grade (MBG) is an angiographic measure of myocardial perfusion. We hypothesized that optimal angiographic reperfusion is defined by TIMI 3 flow and MBG 2 or 3. Methods and Results—In 924 consecutive patients with TIMI 3 flow after angioplasty for acute myocardial infarction, we prospectively studied the value of MBG. End points were death, MACE, enzymatic infarct size, and residual left ventricular ejection fraction. Follow-up was 16±11 months. Of the 924 patients, 101 (11%) patients had MBG 0 or 1. Mortality was significantly higher in patients with MBG 0 or 1 compared with patients with MBG 2 or 3 (relative risk, 4.7; 95% CI, 2.3 to 9.5;P <0.001). The combined incidence of MACE was higher in patients with MBG 0 or 1 compared with patients with MBG 2 or 3 (relative risk, 1.8; 95% CI, 1.1 to 2.8;P =0.009). Enzymatic infarct size was larger (1437±2388 versus 809±1672, P =0.001) and left ventricular ejection fraction was lower (37.7±10.6 versus 43.8±11.1, P <0.001) in patients with MBG 0 or 1 compared with patients with MBG 2 or 3. Conclusions—MBG is a strong angiographic predictor of mortality in patients with TIMI 3 flow after primary angioplasty. Enzymatic infarct size is larger and residual left ventricular ejection fraction is lower in patients with MBG 0 or 1 compared with MBG 2 or 3. Angiographic definition of successful reperfusion should include both TIMI 3 flow as well as MBG 2 or 3.

Reperfusion therapy in elderly patients with acute myocardial infarction: A randomized comparison of primary angioplasty and thrombolytic therapy

OBJECTIVES This study sought to determine the short- and long-term outcome of primary coronary angioplasty and thrombolytic therapy for acute myocardial infarction (AMI) in patients older than 75 years of age. BACKGROUND The benefit of reperfusion therapy in elderly patients with AMI is uncertain, although elderly people account for a large proportion of deaths. METHODS We randomly assigned a total of 87 patients with an AMI who were older than 75 years to treatment with angioplasty or intravenous (IV) streptokinase. Clinical outcome was measured by taking the end points of death and the combination of death, reinfarction or stroke during follow-up. RESULTS The primary end point, a composite of death, reinfarction or stroke, at 30 days had occurred in 4 (9%) patients in the angioplasty group as compared with 12 (29%) in the thrombolysis group (p = 0.01, relative risk [RR]: 4.3, 95% confidence interval [CI]: 1.2 to 20.0). At one year the corresponding figures were 6 (13%) and 18 (44%), respectively (p = 0.001, RR: 5.2, 95% CI: 1.7 to 18.1). CONCLUSIONS In this series of patients with AMI who were older than 75 years, primary coronary angioplasty had a significant clinical benefit when compared with IV streptokinase therapy.

Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction ☆: The glucose-insulin-potassium study: a randomized trial

OBJECTIVES In this study we considered the question of whether adjunction of glucose-insulin-potassium (GIK) infusion to primary coronary transluminal angioplasty (PTCA) is effective in patients with an acute myocardial infarction (MI). BACKGROUND A combined treatment of early and sustained reperfusion of the infarct-related coronary artery and the metabolic modulation with GIK infusion has been proposed to protect the ischemic myocardium. METHODS From April 1998 to September 2001, 940 patients with an acute MI and eligible for PTCA were randomly assigned, by open-label, to either a continuous GIK infusion for 8 to 12 h or no infusion. RESULTS The 30-day mortality was 23 of 476 patients (4.8%) receiving GIK compared with 27 of 464 patients (5.8%) in the control group (relative risk [RR] 0.82, 95% confidence interval [CI] 0.46 to 1.46). In 856 patients (91.1%) without signs of heart failure (HF) (Killip class 1), 30-day mortality was 5 of 426 patients (1.2%) in the GIK group versus 18 of 430 patients (4.2%) in the control group (RR 0.28, 95% CI 0.1 to 0.75). In 84 patients (8.9%) with signs of HF (Killip class > or =2), 30-day mortality was 18 of 50 patients (36%) in the GIK group versus 9 of 34 patients (26.5%) in the control group (RR 1.44, 95% CI 0.65 to 3.22). CONCLUSIONS Glucose-insulin-potassium infusion as adjunctive therapy to PTCA in acute MI did not result in a significant mortality reduction in all patients. In the subgroup of 856 patients without signs of HF, a significant reduction was seen. The effect of GIK infusion in patients with signs of HF (Killip class > or =2) at admission is uncertain.

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes

BACKGROUND Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. METHODS We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. RESULTS The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34). CONCLUSIONS In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).

Prognostic Assessment of Patients With Acute Myocardial Infarction Treated With Primary Angioplasty Implications for Early Discharge

Background—The aim of this study was to create a practical score for risk stratification in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary angioplasty and to assess the feasibility of early discharge in low-risk patients. Methods and Results—A prognostic score was built according to 30-day mortality rates in 1791 patients undergoing primary angioplasty for STEMI. For the identified low-risk patients without any contraindication to early discharge, we estimated and compared the costs of conventional care (prolonged 24-hour hospitalization) with the costs of shifting the care from inpatient to outpatient setting (early discharge) between 48 and 72 hours. Independent predictors of 30-day mortality included in the score were age, anterior infarction, Killip class, ischemic time, postprocedural Thrombolysis In Myocardial Infarction (TIMI) flow, and multivessel disease. This score was able to identify a large cohort (73.4%) of low-risk (score ≤3) patients, with a good discriminatory capacity (c statistic=0.907). The mortality rate was 0.1% at 2 days and 0.2% between 2 and 10 days in patients with a score ≤3. The incremental cost-effectiveness ratio for late discharge in low-risk patients was estimated at &U20AC;1949.33. Therefore, this policy would save 1 life per 1097 low-risk patients, at additional costs of &U20AC;194 933.33, in comparison with an early discharge policy. Conclusions—This score is a practical and useful index for risk stratification after primary angioplasty for STEMI, with a significant impact on clinical decision-making and the related costs. It reliably identifies a large group of patients at very low risk, who may safely be discharged early after primary angioplasty.