Aim

To compare the efficacy of prompt fibrinolysis coupled with contemporary antiplatelet and antithrombotic therapy at first medical contact followed by timely catheterisation in patients with STEMI within 12 h of symptom onset (ie, a pharmacoinvasive strategy) in comparison with standard primary PCI.

Study design

This is a prospective, observational, multicentre pilot study which was conducted from August 2011 to May 2013. We carried out this study as there is a strong rationale for assessing feasibility through piloting the pharmacoinvasive strategy in Indian patients presenting with STEMI, as there is little that is known about the same. The study sites are situated in South India; three sites are from the state of Tamil Nadu, one from the state of Karnataka and one from the state of Kerala. All study sites were well equipped with 24/7 facility of performing primary PCI with the aid of expert interventional cardiologists. A total of 200 patients diagnosed to have STEMI were enrolled into the study based on the inclusion/exclusion criteria. No randomisation for this study was performed due to ethical reasons, as most Indian patients with STEMI have longer presentation times compared with patients from developed countries.6 Although all participating hospitals are primary PCI capable hospitals, some patients opted for a pharmacoinvasive approach. The main reason for this is lack of ready finances. Comprehensive insurance coverage for all comers with STEMI was not available at all participating centres during the period of the study as STEMI care was not linked to insurance. Applying for insurance or arranging for out of pocket expenses needed time; hence, patients opted for a thrombolysis initially, and then went ahead with catheterisation and PCI once the insurance approval came or money could be arranged. This was the reason in the majority of patients who went through the pharmacoinvasive strategy. In a minority of patients, the catheterisation laboratory was not available at the time of the patient's arrival. (Out of 45 patients in group A, only one patient underwent the pharmacoinvasive approach because the catheterisation laboratory was occupied.) Failed thrombolysis is defined as persisting or worsening chest pain or <50% resolution of ST-segment elevation after 90 min of thrombolysis in a single lead showing maximum ST-segment elevation at presentation. Written informed consent was signed by all patients.

The inclusion criteria were the following: adults aged 18–75 years with STEMI requiring either primary PCI or fibrinolysis with TNK, patients presenting with the onset of symptoms within 12 h, subjects/legally acceptable representative or impartial witness (if applicable) must be able to understand and provide their consent in the informed consent form. If a patient with STEMI has unstable haemodynamics or is not willing to read and sign the informed consent during initial presentation, then a legally acceptable representative, that is, a family member, could initially sign the informed consent. As we still have illiterate patients and family members in India, we often use a person who is not related to the study to read out the informed consent to the patient and the family members and then obtain a thumb print from them. The person who reads the consent is often called the ‘impartial witness’ and needs to sign the informed consent form as well. Patients who were participating in any other study or who were unwilling to comply with the protocol were excluded.

End points

The primary end point was a composite of death, cardiogenic shock, reinfarction, repeat revascularisation of the culprit artery and congestive heart failure at 30 days. The safety end points are bleeding end points assessed using the thrombolysis in myocardial infarction (TIMI) classification at 30 days.

Definitions used in the study are given in the online supplementary appendix.

Study protocol

Data were collected by personnel who were blinded to the study objectives and recorded the same in specially designed electronic case report form (eCRF). Each patient was given a screening number to maintain anonymity. Demographic details and baseline characteristics of the patient population were documented meticulously. Relevant medical history, salient clinical examination findings, laboratory investigations including cardiac biomarkers, ECG and echocardiogram findings were noted. Details of medication prescribed were also collected. Patients who were fibrinolysed with TNK were in group A and patients who underwent primary PCI formed group B. Figure 1 depicts the study flow. In group A, the timing and dosage of TNK was documented, and TNK was administered as per the recommended dosage based on the body weight of the patient, 30 mg if the weight is <60 kg, 35 mg if the weight is 60–70 kg, 40 mg if the weight is 70–80 kg, 45 mg if the weight is 80–90 kg and 50 mg if the weight is >90 kg. In case of failed thrombolysis, rescue PCI was performed at the investigator's discretion. The time to a coronary angiogram (CAG) with or without intervention, time from symptom onset to hospital presentation, door-to-balloon time, door-to-needle time and total ischaemic time were documented. During the procedure, the access site, whether or not thrombosuction was performed, the number of vessels diseased, the number of vessels stented, the type of stent used, the reasons for not performing angioplasty if the procedure was not conducted, the procedure complications if any, the adjuvant medication, the use of intra-aortic balloon pulsation and the outcome of the procedure were noted.The IRA patency, TIMI flow in IRA preprocedure and postprocedure, thrombus burden and procedure success were evaluated by a blinded investigator. Bleeding events were classified using TIMI bleeding criteria.

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Figure 1

Study protocol of Study comparing TEnecteplase facilitated PCI versus Primary PCI in Indian patients with Acute Myocardial Infarction (STEPP-AMI). ASA, Aspirin; TNK, Tenecteplase; PCI, percutaneous coronary intervention; LD, loading dose; OD, once daily; LMWH, low-molecular-weight heparin. *Please refer to the text for the definition of failed thrombolysis.

At discharge, patients’ clinical status and prescription details were also noted. Follow-up was done at the clinic at 30 days, and telephonically at 3, 6 and 12 months. During follow-up angina status, functional status and details about any reportable events were collected.

Statistical analysis

A sample size of 200 patients was enrolled as this was a pilot study primarily designed to assess feasibility. Data from all five study sites were combined for analysis. All statistical analyses were performed using SAS software, V.9.2. Continuous data were presented as n (observation count), mean, SD, minimum, median and maximum. Categorical data and the number and percentage of participants in each category were reported. We used frequency and cross tabulation to explore differences across different factors. Continuous variables were tested using the Student t test and the categorical variables were tested using the χ²/Fischer's test for the relation between each individual factor and treatment group at 5% level of significance. The total ischaemic time between the two groups was compared using the median test at 5% level of significance. Relative risk estimates were calculated along with 95% CIs and provided in the appropriate tables along with adjustments for important covariates. The Kaplan-Meier curves with log rank test were used to compare differences in outcomes as well. A p value of 0.05 was considered significant for all statistical evaluations.