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Primary stenting in selected patients with AMI appears to be more effective than PTCA or fibrinolytic therapy,^2,3,6-18 but not all infarct-related arteries are suitable for stenting. A primary stenting strategy incorporating primary stenting, PTCA, coronary artery bypass grafting (CABG) or medical treatment (except fibrinolytic therapy) is expected to cater for all patients. We examined prospectively the feasibility and clinical outcomes to 6 months of a primary stenting strategy in patients with AMI who were eligible for fibrinolysis.

Patient selection
Patients included: 102 patients fulfilled GUSTO criteria for AMI,⁵ and were eligible for fibrinolysis. A lower age limit was imposed during the first half of the study (during the learning curve for the stenting team), and patients with previous CABG were excluded because stenting was initially thought to be less effective in vein-graft occlusion. Accordingly, the first 50 patients were under 70 years and had not had CABG. The following 52 patients, two of whom had had CABG, were under 80 years.

Patients excluded: Reasons for non-entry to the study in 92 patients were age limit exceeded (over 70 years, 47 patients; over 80 years, 23 patients); transfer from other hospitals for primary intervention (5 patients); not eligible for fibrinolysis, including two with cardiogenic shock (8 patients); no vascular access (2 patients); prior CABG (2 patients); cardiogenic shock (1 patient); eligible but refused (2 patients); and eligible but interventional cardiologist unavailable (2 patients).

Ethical approval
The protocol was approved by the hospital's Human Research and Ethics Committee. All patients gave informed consent.

Study protocol
Patients were given aspirin (300 mg), ticlopidine (500 mg) and an intravenous heparin bolus (150 U/kg), and transferred immediately to the catheterisation laboratory, or, out of working hours, as soon as the interventional team arrived. Low-osmolar ionic contrast medium (sodium ioxaglate) was used to minimise thromboembolic complications.¹⁹

Blood flow was re-established in the occluded infarct-related arteries with Magnum (Schneider, Bulach, Switzerland) 0.014 inch wire through a 6 French (2 mm diameter) guide. Placement of a stainless steel stent (the majority were GFX (Arterial Vascular Engineering, Santa Rosa, Calif, USA) by high pressure balloon inflation (> 10 atmospheres) was attempted in vessels with a reference segment diameter of more than 2.5 mm and a lesion length of less than 32 mm. Thrombus was not considered a contraindication to stenting. Fibrinolytic therapy was not given.

Medical treatment only was given (aspirin, heparin, -blockers) if, after cardiac catheterisation, the infarct-related artery was patent with normal brisk flow (ie, grade 3 flow as defined by the Thrombolysis in Myocardial Infarction [TIMI] trial²⁰), and had residual stenosis of less than 50% of vessel diameter.

Emergency (immediate) or inhospital CABG was performed for left main coronary artery and/or severe triple-vessel disease, and PTCA was performed when the diameter of the infarct-related artery was less than 2.5 mm.

A glycoprotein IIb/IIIa receptor antagonist (abciximab) was given to 23 of the 102 patients: 11 patients having primary PTCA, 3 patients in whom reflow did not occur, and 9 patients with persistent filling defects or a long stented segment (> 18 mm). Further heparin was given if activated clotting time (for monitoring high dose heparin) was under 300 seconds. No further heparin was given after the procedure and patients were mobilised 12 hours after femoral sheath removal.

Ticlopidine (250 mg daily) was administered for 4 weeks and patients were monitored for side effects (neutropenia, thrombocytopenia).

All patients were followed up by their general practitioner and specialist physician. Follow-up for the trial was at 6 weeks and 6 months; patients completed questionnaires or, if necessary, were interviewed by phone.

Outcome measures
Study outcome measures were major adverse cardiac and cerebrovascular events: death, reinfarction, cerebrovascular accident (CVA) and repeat target lesion revascularisation, in hospital, and at 6 weeks and 6 months.

Reinfarction was defined as recurrent ischaemic symptoms with changes noted on the electrocardiogram (ECG) (ST-segment elevation or new Q waves) and elevation in the level of creatine kinase (MB fraction) to more than twice the upper limit (normal range, 0-7 µg/L) or any rise above a previously elevated level.

CVA was defined as new persistent (> 24 hours) neurological deficit consistent with a stroke, confirmed by a physician or by computed tomography scan of the brain.

Patency of the infarct-related artery was determined by TIMI classification.²⁰

Minor inhospital adverse events included bleeding requiring blood transfusion, vascular complications and new-onset heart failure.

Successful procedural outcome was a patent infarct-related artery with residual stenosis of less than 30% of vessel diameter (without major adverse cardiac and cerebrovascular events in hospital), or uncomplicated CABG.

There were no inhospital deaths, reinfarctions or CVAs. Four patients (4%) required repeat target lesion revascularisation (three had been treated initially with PTCA and one with stenting). Unscheduled recatheterisation was performed in another four patients with chest pain, without ECG changes. All showed a widely patent stent. No patient developed recurrent chest pain with ECG changes while in hospital.

Minor inhospital events included blood transfusion, all after CABG (7/102; 7%), new-onset heart failure (2/102; 2%), and femoral artery pseudoaneurysm requiring surgical repair (2/102; 2%).

For more information see flow chart

Six-week and 6-month follow-up
Follow-up was completed for all patients due for follow-up at 6 weeks (n = 102) and at 6 months (n = 58).

At 6 weeks no deaths or CVAs had occurred. One patient had had a reinfarction after a subacute stent thrombosis on Day 10. He underwent successful repeat PTCA (reperfusion at sites other than the target lesion was not performed). Major adverse cardiac or cerebrovascular events had occurred in 5/102 patients: one had a reinfarction after discharge and four required repeat target lesion reperfusion.

At 6 months, still no deaths had occurred, and there had been no further reinfarctions or CVAs. Clinical restenosis requiring repeat target lesion revascularisation occurred in an additional 6/58 patients (10%). Revascularisation at a new site of stenosis was performed in 1/58 patients (2%).

No deaths, reinfarctions or CVAs had occurred since discharge, and at 6 months there had not been any requirement for revascularisation in 51/58 patients (88%).

Hospital stay
Mean hospital stay was 5.0 days (95% confidence interval (CI), 4.5-5.5 days). Mean coronary care, intensive care and general ward stays were 1.5 (95% CI, 1.4-1.6), 0.5 (95% CI, 0.3-0.7) and 3.0 days (95% CI, 2.7-3.3), respectively. Median hospital stay was 3 days.

Time delays
Time delays between the onset of chest pain and re-establishment of TIMI 3 flow of the infarct-related artery are shown in Box 2. Although 58% of patients presented out of working hours, only 10% of "call-backs" for the intervention team took place between 23:00 and 04:00.

Coronary artery patency with the primary stenting strategy was achieved in 95% of patients, similar to reports for primary stenting in selected patients,^14-18 but higher than reported for primary PTCA (73%-87%) and fibrinolysis with t-PA (54%).^1,3,7-9 Interestingly, 25% of patients in our study had TIMI 3 flow at cardiac catheterisation, a rate higher than reported by some investigators (7%-11%)¹⁴ and similar to rates after fibrinolysis with streptokinase (29%-32%). We gave a 150 U/kg bolus dose of intravenous heparin, which may explain this difference.²¹

Our results compare favourably with those of other primary stenting studies.^14-18 A 30-day rate of 3% for major adverse cardiac and cerebrovascular events has been reported for patients undergoing primary stenting.^14,15 However, in one of these studies,¹⁴ up to 15% of patients screened were excluded, owing to unsuitable anatomy of the infarct-related artery (eg, diffuse disease), and events in such patients were not included. Several studies report outcomes of patients treated by primary PTCA separately to those treated by stenting,^14-18 making it difficult to directly compare the results with those of trials of fibrinolytic therapy in which all patients are included. We included all patients eligible for fibrinolysis who fulfilled the inclusion criteria in our analysis. This allows a more realistic impression of the benefits of a primary stenting strategy, as our data can be compared with data from trials of fibrinolytic therapy (the alternative treatment offered to all patients at enrolment).

Feasibility
In order to test the feasibility of a primary stenting strategy (our main aim), our emergency department had to triage patients without delay and the interventional team had to respond swiftly at all hours. Time delays (mean and median) from arrival at the emergency department to notification of the interventional team (42 and 35 minutes), from notification of the team to TIMI 3 flow (64 and 60 minutes), and from arrival at the emergency department to TIMI 3 flow (106 and 95 minutes), compare well with time delays from trials of fibrinolysis and angioplasty. The GUSTO investigators reported a median interval of 64 minutes from randomisation to administration of fibrinolytic therapy,⁵ and the GUSTO IIb investigators reported a median interval of 114 minutes from emergency department arrival to first balloon inflation in the primary PTCA group.¹⁰

Patency rates are reported 90 minutes after starting fibrinolytic therapy.¹ Assuming a mean delay of 42 minutes in the emergency department to administration of fibrinolytic therapy, the equivalent inhospital delay from emergency department arrival to TIMI 3 flow with fibrinolytic therapy would be a mean of 132 minutes (but TIMI 3 flow would actually be achieved in only 54% of patients). We achieved TIMI 3 flow in 95% of patients within a mean of 106 minutes of arrival at the emergency department.

Limitations of the study
This study was a non-randomised, single-centre study with a small sample size. For the first half of the study, enrolment was restricted to a relatively low risk group under 70 years of age without previous CABG. Interventions were performed by two experienced operators. Thus, comparison of our data with results from much larger trials of fibrinolytic therapy must be performed with caution.

Conclusions
A primary stenting strategy is feasible and safe, with an excellent clinical outcome to 6 months. We are now planning a larger, randomised phase of this study, with patients from the Northern Sydney Area Health Region (which includes four district hospitals) outside the Royal North Shore Hospital (RNSH) catchment area being allocated at random to either conventional treatment with fibrinolytic therapy at the district hospital or a primary stenting strategy at RNSH. We hypothesise that mechanical reperfusion therapy will prove the superior strategy because of its higher early patency rate³ and offset any disadvantages of the small time difference imposed by a longer ambulance journey.

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Reprints: Dr G I C Nelson, Department of Cardiology, Royal North Shore Hospital, St Leonards, NSW 2065.

©MJA 1999
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