Final benefit of primary percutaneous coronary intervention for ST-elevation myocardial infarction in older patients: long-term results of a randomised trial

From March 1996 until April 1999, 87 patients aged 76 years or older referred directly to our hospital with STEMI and without contraindications for thrombolytic therapy were randomly assigned to treatment with intravenous streptokinase or immediate angiography and, if possible, subsequent angioplasty. Inclusion criteria were as follows: symptoms of STEMI that persisted for more than 30 min accompanied by an elevation of more than 1 mm (0.1 mV) in the ST segment in two or more contiguous electrocardiographic leads; and presentation within 6 h after the onset of symptoms (or between 6 and 24 h if there was evidence of continuing ischaemia). Contraindications to thrombolytic therapy were defined as previous stroke or other known intracranial diseases, recent trauma or surgery, refractory hypertension (systolic > 180 mmHg, diastolic > 110 mmHg), active bleeding or prolonged cardiopulmonary resuscitation. Before randomisation we recorded each patient’s age, gender, Killip class on admission, electrocardiographic site of infarction, history of previous infarction, heart rate, time of onset of symptoms and time of hospital admission. The catheterisation laboratory and the dedicated house staff were available 24 h, 7 days a week. All patients received 450 mg aspirin intravenously, followed by 80 mg aspirin/day orally and intravenous nitroglycerin at a dose designed to maintain a systolic blood pressure of 110 mmHg. Intravenous heparin was given at a dose designed to maintain the activated partial thromboplastin time between two and three times the normal value for at least 2 days. The partial thromboplastin time was measured twice a day. Patients assigned to streptokinase received 1.5 million U intravenously over a period of 1 h. In patients assigned to angioplasty treatment, coronary angiography was performed as soon as possible. Both coronary arteries were visualised; left ventriculography was not performed routinely. Coronary angioplasty was performed at the investigator’s discretion using standard techniques and devices. Patients who received a stent were treated with ticlopidine, 250 mg, twice a day for 2 weeks. All angiograms were reviewed by two experienced investigators not involved in other parts of the study. Flow through the infarct-related vessel (IRV) was scored according to the Thrombolysis In Myocardial Infarction (TIMI) flow grading system, before and after the angioplasty procedure. Agreement on flow and extent of coronary artery disease was reached in all cases. The time from admission to the initiation of therapy was calculated as the time to the start of the streptokinase infusion or the first balloon inflation. Recurrent myocardial infarction was defined as chest pain, changes in the ST‑T segment and a second increase in the creatine kinase level to more than two times the upper limit of normal or an increase of > 200 U/l over the previous value if the level had not dropped below the upper limit of normal. The primary endpoint was the composite of death, reinfarction or stroke at 30 days after randomisation.

Data about survival were available for all patients until February 2021. The life expectancy of the study population was compared with that of the general Dutch population (https://​opendata.​cbs.​nl/​statline/​#/​CBS/​nl/​dataset/​37360ned/​table?​fromstatweb), adjusted for year of inclusion in the study, age and gender. Study approval was obtained from the medical ethics committee of Isala Hospital.

Statistical analysis was performed with the Statistical Package for the Social Sciences version 20.0 (SPSS Inc., Chicago, IL, USA). Continuous data are expressed as mean ± standard deviation and categorical data as a percentage, unless otherwise denoted.

The baseline characteristics are summarised in Tab. 1. The two patient groups were well balanced with regard to the most important determinants of mortality and morbidity. Six patients in the group assigned to PCI and four in the streptokinase group were randomised more than 6 h after symptom onset (p = 0.7).

Of note is that the study was halted prematurely because of ethical issues raised by the medical ethics committee, after the results of the first 80 patients had been analysed.

Of the patients randomised to invasive treatment, 45 underwent coronary angiography, and 41 actually underwent PCI with a procedural success rate of 90% (37 of 41), defined as a residual stenosis of the culprit lesion of < 50% and TIMI 3 flow through the IRV. One patient died before angiography could be performed. Two patients were referred for bypass surgery, and in two patients a conservative treatment was chosen. Four strokes occurred, in one patient in the angioplasty group (1 week after treatment with an intra-aortic balloon pump) and three in the streptokinase group (all on the day of treatment), one of whom died.

After 30 days, three patients (7%) in the angioplasty group had died, compared with nine patients (22%) in the thrombolysis group (p = 0.04), resulting in an RR of 4 for death (95% CI: 0.9–24.6) for patients treated with thrombolysis. The composite predefined endpoint of death, recurrent infarction and/or stroke at 30 days occurred in 4 (9%) patients in the angioplasty treated patients versus 12 (29%) in the thrombolysis group (p = 0.01).

By January 2021, all the patients had died. Mean survival was 6.0 years (SD 5.0). Maximum survival was 20 years. The patients randomised to streptokinase died after a mean follow-up duration of 5.2 years (SD 4.9) compared to 6.7 years (SD 5.0) in patients randomised to primary PCI (p = 0.15). Thus, the mean final survival benefit of primary PCI was 1.5 years. Long-term survival is depicted in Fig. 1.

The life expectancy of the general Dutch population, adjusted for year of inclusion, age and gender was 7.65 years, demonstrating that the life expectancy of patients treated with thrombolysis was 2.45 years and of the patients treated with primary PCI 0.95 years shorter as compared to the general population.