The study population for this retrospective study comprised all patients who underwent PCI between March 2014 and November 2016 at King George’s Medical University, Lucknow, India. The major inclusion criteria included a reported incidence of acute and early stent thrombosis post-PCI. In order to analyse the outcomes in real-world population, no additional clinical descriptors or angiographic exclusion criteria were defined. The protocol of the study was approved by Institutional Ethics Committee and the study conformed to the principles of good clinical practice and the Declaration of Helsinki.

The data used for the analysis in this study were retrieved from the patient records maintained at the institute. In these reports, the data on demographic features, presence of coronary risk factors, and past medical history had been documented at the time of admission, while the details of affected lesions and implanted stents had been noted during the index procedure. Incidence of stent thrombosis and outcomes for these patients were specifically analysed.

Events of stent thrombosis were determined based on the criteria laid by the Academic Research Consortium (ARC) and were classified in to definite (angiographic or pathologic evidence), probable (unexplained death within 30 days of the procedure or MI at any time in the territory of previous PCI), and possible (unexplained death occurring 30 days post procedure) stent thrombosis [9]. Additionally, the events of stent thrombosis were categorised as acute (<24 hours post procedure), early (24 hours to 30 days post procedure), late (31 days to one year post procedure) and very late (>one year post procedure). Early stent thrombosis were further grouped into intra-procedural (during the procedure) and sub acute, from the end of the procedure to 30 days thereafter [1,4]. Here, the term stent thrombosis was collectively used for acute as well as early stent thrombosis. Incidence of stent thrombosis was calculated as the number of patients with stent thrombosis divided by total number patients who underwent PCI with stenting during the study period.

All data were analysed using the Statistical Package for Social Sciences (SPSS; Chicago, IL, USA) program, version 15.0. Continuous variables are presented as mean±standard deviation, while categorical variables are presented as frequency and percentages. For the statistical comparison between the two groups, the non parametric Student’s t-test (i.e., the Mann-Whitney U test) was used for continuous variables (i.e., age, onset of symptoms, ejection fraction, and number of stents) and the chi-square test or the Fisher’s-exact test was used for categorical variables (i.e., males, smoking, diabetes mellitus, STEMI, primary PCI, multi-vessel disease, intra-procedural GpIIb/IIIa use, and clopidogrel prescription). A two-sided alpha level of 0.05 was used to identify statistically significant difference between two groups.

A total of 3,869 PCI were performed at our institute. Of them, the incidence of early and acute stent thrombosis was noted in 41 (1%) patients. Data of these 41 patients (mean age: 54.0±10.5 years) were examined extensively in the present study. Of this study population, 36 (87.8%) were males, 12 (29.3%) were diabetic, 8 (19.5%) were hypertensive, 6 (14.6%) were dyslipidaemic, and 19 (46.3%) were smokers and multiple risk factors were present in seven patients. For these patients, angina status prior to PCI revealed STEMI in 30 (73.2%) patients (anterior-wall STEMI, inferior-wall STEMI, posterior-wall STEMI in 21 (51.2%), 8 (19.5%), and 1 (2.4%) patients respectively), NSTEMI in 7 (17.1%) patients, unstable angina in 1 (2.4%) patient, and stable angina in 3 (7.3%) patients. Other demographic characteristics of the study population are described in [Table/Fig-1].

For the study population, single-vessel disease was present in 22 (53.7%) patients while multi-vessel disease was noted in the 19 (46.3%) patients. PCI was performed in 49 lesions with target coronary vessel being left anterior descending artery in 31 (63.3%) cases, left circumflex artery in 7 (14.3%) cases, and right coronary artery in 11 (22.4%) cases. Site of culprit lesion were ostial, proximal, mid, and distal in 8 (16.3%), 29 (59.2%), 11 (22.5%), and 1 (2.0%) cases. Of these, thrombus was present in 24 (49.0%) lesions and 8 (16.3%) were calcified lesions, while total occlusion was observed in 8 (16.3%) lesions. [Table/Fig-2,3] describe the lesion and procedural characteristics of the patients respectively. A total of 51 stents were implanted with mean size of 27.3±6.6 mm length and 2.9±0.3 mm diameter. Of STEMI patients, 6 had their primary angioplasty done in window period, 16 patients received thrombolytic therapy prior PCI within the window period, while 8 patients were admitted late and did not qualify the criteria of window period for receiving thrombolytic therapy. Pre-dilation and post-dilation was performed for 34 (69.3%) and 38 (77.5%) lesions respectively. Intra-procedural GPIIb/IIIa was used in 10 (24.4%) patients. Procedure was uneventful in 26 (63.4%) patients, while intra-procedural complications of slow flow, no flow, dissection, hypotension, and hypotension with cardiogenic shock was noted in 5 (12.2%), 2 (4.9%), 2 (4.9%), 4 (9.8%), and 2 (4.9%) patients respectively. End result was TIMI Grade III flow in 38 (92.7%) patients and TIMI Grade II flow in 3 (7.3%) patients. Details of various stents used in the PCI procedures for these patients that experienced are given in [Table/Fig-4].

Of 41 cases of early stent thrombosis, 29 (70.7%) were definite and 12 (29.3%) were probable stent thrombosis. These patients were managed appropriately with thrombosuction in 23 (56.1%) cases, thrombolysis therapy in 4 (9.8%) cases, POBA in 24 (58.5%) cases, and conservative therapy using infusion of GPIIb/IIIa inhibitors in 12 (29.3%) cases. However, mortality was reported in 18 (43.9%) patients, while 23 (56.1%) patients were discharged successfully in a stable state. Of those died, 8 (44.4%) patients died before they could be taken up for emergency PCI before they had died. Overall, 17 (41.5%) died due to cardiac death, 1 (2.4%) patient died due to non cardiac death, 11 (26.8%) patients had experienced re-infarct, and 1 (2.4%) patient had experienced stroke. The outcomes of stent thrombosis are described in [Table/Fig-5].

A comparative analysis of various demographic, clinical and procedural characteristics between patients who died after the onset of stent thrombosis and patients who survived after the onset of stent thrombosis was performed. The outcomes for this analysis are given in [Table/Fig-6]. Interestingly, the onset of symptoms (days) to initial presentation to hospital was significantly shorter in patients who died than that in patients who survived (27.11±44.9 vs. 62.8±99.8; p=0.013). Other factors including age, gender, ejection fraction at presentation, smoking, diabetes mellitus, STEMI, primary PCI, thrombotic lesion, multi-vessel disease, intra-procedural use of GPIIb/IIIa inhibitors, or prescription of clopidogrel were statistically comparable between two groups.

Early stent thrombosis (≤30 days after stent implantation) is a relatively rare however most feared complication related to coronary stent placement PCI [10]. In present study, early stent thrombosis was identified in 41 (1%) of the 3,869 patients implanted with drug-eluting stent during the study period. This finding is encouraging as the incidence reported in present study is comparatively lower than the available literature [3,5,11-14].

In general, the underlying mechanism of stent thrombosis is multifactorial and includes various patient-related, lesion-related, stent-related, procedure-related, and post-procedure related factors. The patient-based factors comprise presence of acute myocardial infarction, acute coronary syndrome, diabetes mellitus, renal failure, low ejection fraction, younger age, and smoking. The lesion-based factors comprise diffuse disease, small-vessel disease, bifurcation lesion, chronic total occlusion, and thrombus-containing lesions. Stent-related factors comprise role of antiproliferative agent, coating technologies, polymer biocompatibility, stent material, strut/polymer thickness, stent structure, and drug dosage. The procedure-related factors comprises stent underexpansion, stent malapposition, stent length, multiple stents, persistent slow flow, residual stenosis, edge dissections, and development of neoatherosclerosis within stents with new plaque rupture. The post procedure related factors include type and duration of antiplatelet therapy and adherence to prescribed regimen [7,15]. Based on these, it is recommended to have strict attention on patients’ risk factor profile and their ability to adhere to prescribed medical regimens before proceeding with stent implantation. In addition, all interventional cardiologists should take utmost care to technical details in order to optimise stent implantation and deployment, particularly in complex disease [7]. In the present study, substantial presence of these risk factors was observed among patients with early stent thrombosis, including diabetes (29.3%), smoking (46.3%), STEMI (73.2%), chronic total occlusion (16.3%), thrombus-containing lesion (49%), Type C lesions (73.5%), and intra-procedural complications (36.7%). We believe that the occurrence of stent thrombosis can be minimised with careful patient section and stent selection and deployment.

In the present study, we also analysed the clinical consequences of stent thrombosis in the study cohort. Of patients with early stent thrombosis, we found that 70.7% cases were definite and 29.3% cases were probable stent thrombosis. Although all patients were aimed to manage appropriately, morality was reported in 43.9% patients and re-infarct was reported in 26.8% patients. Although, the mortality rates in the present study are comparable with that reported in literature [8]. it should be noted that eight patients had died before they could be taken up for emergency. Furthermore, we observed no statistically significant difference for majority of demographic, clinical and procedural characteristics between patients who died after the onset of stent thrombosis and patients who survived after the onset of stent thrombosis. This finding signifies that appropriate and timely treatment is the most important predictor of survival after stent thrombosis, while the demographic, clinical, and procedural characteristics play no role. We opine that the present study fittingly turns the attention to the deleterious issue of early stent thrombosis and its clinical consequences in Indian setting.

This study has several important limitations; it was a retrospective observational study and study population was confined to patients who presented with early (acute or subacute) stent thrombosis. The sample cohort included only 41 consecutive patients with reports of early stent thrombosis from a single-centre; subclinical stent thrombosis may have occurred in some patients but remained undetected. Also, the incidence of late or very late stent thrombosis was not analysed. The outcomes were not compared between various material of stents used in the study. Despite these limitations, the present study is valuable as it describes the incidences and patient/lesion/procedural characteristics of patients experiencing early stent thrombosis in an Indian setting. Further studies examining a larger cohort of patients, incidence of late and very late stent thrombosis, and a comparative analysis of characteristics between patients with and without stent thrombosis are warranted.

In the present study, various established risk factors of early stent thrombosis including diabetes, smoking, STEMI, chronic total occlusion, thrombotic lesion, complex lesion, and intra-procedural complications were substantially present among the patients with early stent thrombosis. We believe that the occurrence of stent thrombosis can be minimised with careful patient section and stent selection and deployment. In the present study cohort, we observed a high incidence of myocardial infarction and death among patients with early stent thrombosis. We are of opinion that appropriate and timely management is most critical for the survival of the patients after early stent thrombosis.