A comparison of outcomes with adjunctive and delayed routine pharmacoinvasive percutaneous coronary intervention strategy after thrombolysis in patients with ST-elevation myocardial infarction: Experience from a tertiary-care center in India

Akhil Kumar Sharma; Vikas Kumar; Gaurav Kumar Chaudhary; Mahim Saran; Varun Shankar Narain; Sudhanshu Kumar Dwivedi; Sharad Chandra

doi:10.4103/heartindia.heartindia_31_18

ORIGINAL ARTICLE

Year : 2018 | Volume : 6 | Issue : 4 | Page : 141-147

A comparison of outcomes with adjunctive and delayed routine pharmacoinvasive percutaneous coronary intervention strategy after thrombolysis in patients with ST-elevation myocardial infarction: Experience from a tertiary-care center in India

Akhil Kumar Sharma¹, Vikas Kumar², Gaurav Kumar Chaudhary¹, Mahim Saran¹, Varun Shankar Narain¹, Sudhanshu Kumar Dwivedi¹, Sharad Chandra¹
¹ Department of Cardiology, King Georges' Medical University, Lucknow, Uttar Pradesh, India
² Department of Cardiology, JVN Heart Hospital, Patna, Bihar, India

Date of Web Publication

17-Dec-2018

Correspondence Address:
Dr. Akhil Kumar Sharma
Department of Cardiology, King Georges Medical University, Lucknow - 226 003, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/heartindia.heartindia_31_18

Abstract

Objective: Since primary percutaneous coronary intervention (PCI) is not readily available to many patients either due to financial issue or unavailability of invasive cath labs, pharmacoinvasive strategies are now becoming the de facto treatment strategy. The most commonly used strategies are adjunctive PCI (within 3–24 h of thrombolysis) and delayed routine PCI (>24 h to before hospital discharge). However, direct comparison of these two strategies is lacking.
Materials and Methods: In this prospective, observational, single-center study, a total of 113 thrombolysed ST-segment elevation myocardial infarction (STEMI) patients in the adjunctive PCI group and 127 thrombolysed STEMI patients in the delayed routine PCI group were analyzed. At 30-day follow-up, patients were evaluated for all-cause mortality, reinfarction, hospitalization due to angina, hospitalization due to heart failure, and improvement in left ventricular (LV) ejection fraction.
Results: Patients in the adjunctive PCI group and those in the delayed routine PCI group exhibited comparable baseline characteristics. At 30-day follow up, no significant difference was noted in all-cause mortality, reinfarction, hospitalization due to angina, and hospitalization due to heart failure. There was slight trend toward increased composite end-points in the adjunctive PCI group, probably favoring delayed routine PCI (8.85% vs. 4.72%; P = 0.450). There was no significant difference in improvement in LV ejection fraction between two groups (P = 0.671).
Conclusions: Even after 24 h of thrombolytic treatment in STEMI patients, delayed routine PCI can be performed with comparable outcome to that of PCI within 24 h.

Keywords: Coronary angiography, left-ventricular ejection fraction, percutaneous coronary intervention, ST-elevation myocardial infarction, thrombolytic therapy

How to cite this article:
Sharma AK, Kumar V, Chaudhary GK, Saran M, Narain VS, Dwivedi SK, Chandra S. A comparison of outcomes with adjunctive and delayed routine pharmacoinvasive percutaneous coronary intervention strategy after thrombolysis in patients with ST-elevation myocardial infarction: Experience from a tertiary-care center in India. Heart India 2018;6:141-7

How to cite this URL:
Sharma AK, Kumar V, Chaudhary GK, Saran M, Narain VS, Dwivedi SK, Chandra S. A comparison of outcomes with adjunctive and delayed routine pharmacoinvasive percutaneous coronary intervention strategy after thrombolysis in patients with ST-elevation myocardial infarction: Experience from a tertiary-care center in India. Heart India [serial online] 2018 [cited 2023 May 29];6:141-7. Available from: https://www.heartindia.net/text.asp?2018/6/4/141/247573

Introduction

Primary percutaneous coronary intervention (PCI) is recommended treatment of choice for ST-segment elevation myocardial infarction (STEMI) patients.^{[1],[2],[3],[4]} However, widespread availability and affordability of primary PCI is still an important concern in our country. Even after improvement in health facility and awareness, only <20% patients are able to get primary PCI. Thus, thrombolytic therapy continues to be the most common reperfusion modality in our setup.^[5],[6] Nevertheless, thrombolytic therapy has relatively low rates of successful reperfusion.^[7],[8] Even when successful, a significant residual stenosis remains in most patients, which is associated with high rates of recurrent ischemia and reinfarction.^[9] Hence, revascularization is often required afterward in such patients.

In clinical practice, many strategies are available for complete revascularization in patients who received thrombolysis as a primary treatment due to unavailability of primary PCI facility.^{[10],[11],[12]} Rescue PCI refers to PCI that is performed urgently if thrombolysis fails, usually within 60–120 min.^{[13],[14],[15],[16]} Immediate PCI (also known as facilitated PCI) refers to PCI performed within several minutes to hours depending on transfer times, regardless of success of thrombolytic therapy.^{[17],[18],[19]} Adjunctive PCI refers to PCI performed >3 h after, but still within 24 h after thrombolytic therapy. Delayed routine PCI refers to PCI performed >24 h to 2 weeks after thrombolytic therapy, regardless the presence of ischemia or myocardial viability. Delayed selective PCI refers to PCI performed with spontaneous or inducible ischemia after fibrinolysis when appropriate. At present, delayed routine PCI is a Class IIb indication for STEMI, according to the American College of Cardiology (ACC)/American Heart Association (AHA) guideline 2013.^[20]

In spite of the above treatment options in thrombolysed STEMI patients, the optimal timing of intervention is still lacking. Further, current data on different strategies of pharmacoinvasive PCI is limited, with majority of studies comparing primary PCI with fibrinolysis. While facilitated PCI has failed historically, direct comparison of postthrombolysis PCI within 24 h and delayed routine PCI before discharge is very limited in our setup. With this background, we aimed to compare the outcomes of the two pharmacoinvasive strategies, adjunctive PCI, and delayed routine PCI in thrombolysed patients with STEMI.

Materials and Methods

Study design and patient population

This was a prospective, observational, single-center study conducted at the Department of Cardiology King George's Medical University, Lucknow, India, between December 1, 2012 and October 31, 2013. The study population comprised consecutive patients diagnosed with the first occurrence of STEMI and indicated for thrombolysis (age: 18–75 years). Patients undergoing primary PCI or rescue or facilitated PCI were not included in the study. In addition, patients with cardiogenic shock, persistent left ventricular (LV) failure, iatrogenic myocardial infarction, renal failure, mechanical complication, chronic illness, pregnancy, or significant noncardiac comorbidities were excluded. All enrolled patients were managed according to guidelines-directed therapy. They were later on followed closely for complications and feasibility for revascularization and underwent revascularization whenever it was feasible. Accordingly, clinical outcomes of two pharmacoinvasive strategies in postthrombolysis STEMI patients, that is, PCI within 24 h (adjunctive PCI) and PCI before discharge (delayed routine PCI) were compared. The study protocol was approved by the Institutional Ethics Committee and a signed informed content was obtained from each study participant.

Data collection and follow-up

Demographic data and management details were collected from hospital records of discharge summary, angiography reports, and angioplasty reports. All patients were followed-up for 30 days. They were assessed for following clinical end-points: (a) total all-cause mortality, (b) reinfarction, (c) hospitalization due to angina, (d) hospitalization due to heart failure, and (e) improvement in LV ejection fraction (LVEF).

Study definitions

STEMI was defined as symptoms of ischemia associated with ST-segment elevation of ≥1 mm in limb leads and/or ≥2 mm in chest leads in ≥2 contiguous leads or new left bundle branch block on electrocardiogram (ECG). Cardiogenic shock was defined as persistent hypotension with systolic blood pressure <90 mmHg for at least 30 min, despite adequate fluid administration and associated with features of tissue hypoperfusion. Reinfarction was defined as significant rise in myocardial necrosis enzymes (creatinine kinase/troponin T), recurrence of ischemic symptoms with or without new ECG changes. Angina needing hospitalization was defined as recurrence of ischemic symptoms with new ECG changes, which required in-hospital treatment. Mortality at 30 days also includes in-hospital mortality. Similarly, heart failure hospitalization was considered for patient hospitalized with symptoms of heart failure. LVEF was measured by two-dimensional (2D) echocardiography and ultrasound imaging system (GE vivid 7 dimensions, Horten, Norway). The 16-segment model for assessment of LV function, as recommended by the American Society of Echocardiography,^[21] was used. Formal assessment of LV function was performed at admission and then at 30 days by blinded experienced echocardiographers.

Statistical analysis

The collected data were analyzed using the Statistical Package for the Social Sciences (SPSS for Windows version 20.0; Chicago, IL, USA). Categorical variables were presented as frequency and percentage while continuous variables were described as mean value ± standard deviation. The independent Student's t-test and the Chi-square test were used to identify statistical differences between the groups for continuous variables and categorical variables, respectively. P <0.05 was considered to indicate statistically significant difference.

Results

Baseline demographics and management details

The detailed comparative analysis of baseline characteristics and management strategies between the adjunctive PCI group and the delayed routine PCI group are stated in [Table 1].

Table 1: Baseline characteristics and management strategies in patients undergoing adjunctive percutaneous coronary intervention versus delayed routine percutaneous coronary intervention

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Two hundred and forty STEMI patients were included in the study, underwent thrombolysis, and routine investigations including 2D transthoracic echocardiography. According to the time for PCI of an infarct-related artery, patients were divided into two groups – 113 patients in adjunctive PCI group and 127 patients in delayed routine PCI group. The mean age in both the groups was not significantly different (54.23 ± 10.67 vs. 55.86 ± 10.16 years, P = 0.227). Similarly, males were predominant study population as females constituted only 12.4% of participants in the adjunctive PCI group and 19.7% of participants in the delayed routine PCI group. However, the gender distribution between two groups was not statistically significant (P = 0.126). The distribution of diabetes was also not significantly different between two groups (P = 0.947). Mean ejection fraction at admission in both groups was not significantly different (P = 0.379). Further, the presence of heart failure, a high-risk feature, at the time of presentation was also comparable between two groups (P = 0.063).

The median time for thrombolysis for patients in the adjunctive PCI group was 3.5 h and in the delayed routine PCI group was 5.0 h. This difference was statistically nonsignificant (P = 0.323). Further, the difference in type of thrombolytic agents used for the management was not significant statistically (P = 0.385).

Both groups of patients underwent coronary angiography routinely. While patients in the adjunctive PCI group underwent coronary angiography within 24 h of thrombolysis (median: 19 h), in the delayed routine PCI group underwent coronary angiography after 24 h till discharge (median: 60 h). Because of inherent time difference between two groups, it was statistically significant (P < 0.001). The number of patients diagnosed with single-vessel coronary artery disease and double-vessel coronary artery diseases was 78.8% and 21.2% in the adjunctive PCI group and 76.4% and 23.6% in the delayed routine PCI group, respectively. This minor difference does not reach statistical significance (P = 0.659). The use of stent types in both groups was also not statistically significantly different (P = 0.502).

Clinical outcomes

The comparative analysis of clinical outcomes at 30-day follow-up between the adjunctive PCI group and the delayed routine PCI group are stated in [Table 2].

Table 2: 30-day clinical outcomes following adjunctive percutaneous coronary intervention versus delayed routine percutaneous coronary intervention

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The most important outcome in the study was all-cause mortality evaluated as in-hospital mortality and mortality at 30 days. There was a trend toward greater in-hospital mortality in adjunctive PCI group (1.8% vs. 0%), which was not statistically significant (P = 0.132). At 30 days, the gap minimized (1.8% vs. 0.8%) and remained nonsignificant (P = 0.468).

There was a trend toward greater reinfarction within 30 days in the adjunctive PCI group. This difference was not clinically significant (P = 0.132). Here, both cases of reinfarction were due to remaining vessel. Of significance, stents were patent in all cases.

Hospitalization due to angina within 30 days was noted in 3 (2.7%) patients in the adjunctive PCI group as compared to 4 (3.1%) patients in the delayed routine PCI group. This difference was again not statistically significant (P = 0.832). Similarly, the trend for hospitalization due to heart failure was more in the adjunctive PCI group than that in the delayed routine PCI group (2.7% vs. 0.8%), but not statistically significant (P = 0.259).

Although not previously planned, the composite end-point of all-cause mortality, reinfarction, hospitalization due to angina, and hospitalization due to heart failure hospitalization was reported in 10 (8.85%) in the adjunctive PCI group and 6 (4.72%) patients in the delayed routine PCI group, indicating a slight trend toward increased composite end-points in the adjunctive PCI group. However, this difference was again not statistically significant (P = 0.450).

Staged PCI was advised in 18 (15.9%) patients in the adjunctive PCI group and 16 (12.6%) patients in the delayed routine PCI group, which was done in 6 (5.3%) and 12 (9.4%) patients, respectively. Again, these were not significantly different in both groups [Figure 1]; (P = 0.399). Although few patients in both groups had remarkable improvement in LVEF at 30 days, no significant difference was noted between two groups for improvement in LVEF [Figure 2]; (P = 0.671).

Figure 1: Patients needing staged percutaneous coronary intervention following adjunctive percutaneous coronary intervention versus delayed routine percutaneous coronary intervention

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Figure 2: Improvement in left ventricular ejection fraction following adjunctive percutaneous coronary intervention versus delayed routine percutaneous coronary intervention

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Discussion

In developing countries and remote areas of many developed countries, pharmacoinvasive strategy is now the most commonly used approach in the management of STEMI. It is probably the treatment of choice in underdeveloped society, where primary PCI cannot be offered round the clock, both due to financial issue and unavailability of invasive cath-labs capable of doing the same. Despite all efforts, there are many patients who reach capable centers >24 h after thrombolysis. The optimal treatment strategy for such neglected patients is not clear. This issue is not elucidated in any trials. This study was planned to answer a common scenario in developing countries, where health-care facility is still not very well developed. It also applies to those patients living in remote areas of developed countries.

A trial named NORDISTEMI,^[10] conducted for remote areas of Norway, concluded that transfer for PCI after thrombolysis is better than conservative management in remote areas with very long transfer time. Similar findings were noted in TRANSFER-AMI trial.^[12] Both these trials used PCI within 24 h, excluding initial 2–3 h. In another STREAM study,^[22] patients with chest pain of <3 h duration were randomly assigned to thrombolysis therapy, followed by PCI or primary PCI excluding those patients in whom primary PCI is possible within 1 h. In this study, both arms showed comparable outcomes. However, to the best of our knowledge, none of the published trials till date has compared pharmacoinvasive PCI strategies with such a long time between thrombolysis and angiography as in our study. Further, no trial definitely answer the management strategy for patients in which >24 h has elapsed after thrombolysis. Even guidelines are mute in the definite management of such neglected patient, which is very common in developing countries like India.

Our study compared clinical outcomes with two pharmacoinvasive strategies: adjective PCI (within 24 h of thrombolysis) versus delayed routine PCI (24 h to 2 weeks of thrombolysis). Baseline characteristics of two groups (including mean age, gender distribution, diabetes mellitus, heart failure at presentation, mean ejection fraction, severity of coronary artery disease, and type of thrombolytic agent used) were comparable between two groups. Clinical outcomes including total all-cause mortality, reinfarction, hospitalization due to angina, and hospitalization due to heart failure, at 30-day follow-up were nonsignificantly different between the two groups. Further, the composite end-points between two groups was also nonsignificant but showed a trend toward better outcome in delayed routine PCI group (8.85% vs. 4.72%). There was no significant difference in LVEF improvement in both the groups.

This study has an important observation that incidents of reinfarction or hospitalization due to angina were not significantly different in both groups and were solely due to remaining diseased vessel at up to 30-day follow-up. There were 5 (4.43%) patients in the adjunctive PCI group and 4 (3.15%) patients in delayed routine PCI group, who had composite of reinfarction and/or hospitalization due to angina. None of them had stent thrombosis as all had their previous stent patent. Revascularization of remaining vessel was done in these patients. Although not adequately powered, this observation from our study suggests that revascularization of remaining vessel should be done as early as possible, that is, within 30 days. The following explanations may help to explain the overall outcomes observed in our study.

This issue of adjunctive PCI versus delayed routine PCI has not been elucidated in any trials, mainly because it is difficult to randomize STEMI patients for such a long time. According to the present guidelines, nobody should be denied of PCI within 24 h, if applicable
There is strong belief that earlier is better. This is best when primary PCI is applied, in which there is a strong time-dependent decrease in mortality. Once the patient is thrombolysed, the scenario is not the same as for primary PCI. The systemic thrombolytic state is considered to be the factor responsible for detrimental results in facilitated PCI within 3 h of thrombolysis. This systemic thrombolytic state might last for approximately 24 h and may be responsible for not so good outcomes in patients undergoing adjunctive PCI in the present study
The risk of dying of STEMI is highest on day 1. Hence, the patients in our study, who have survived STEMI for >24 h, itself constitute a low-risk population as they have more chances of survival
When >24 h has elapsed, the thrombus is relatively inactive. Hence, there are less chances of adverse phenomenon during PCI, such as no reflow or slow-flow phenomenon. Performing PCI after 24 h when the thrombus has been organized might be beneficial. This concept is nicely utilized in deferred PCI
Antiplatelet needs some time for its peak effect. In our setup, clopidogrel is the most commonly used antiplatelet, which has a slow onset of action. Even 600 mg loading dose of clopidogrel requires 2–3 h for peak effect. Hence, this seems likely that >24 h group must have better antiplatelet drug levels and actions
Use of heparin (or low-molecular-weight heparin) is not very well studied along with nonfibrin specific thrombolytic agents like streptokinase. At our center, it is a common practice to use heparin 6 h after streptokinase. Heparin during PCI may theoretically, further increases the chance of bleeding. It may explain the fatal intracranial hemorrhage occurred in one patient assigned to the adjunctive PCI group (i.e., within 24 h). There was no incident of intracranial hemorrhage in the delayed routine PCI group. This probably also explains that heparin is safer in delayed routine PCI
It can be speculated that use of newer antiplatelet drugs (i.e., prasugrel or ticagrelor) may boost >24 h approach. Literature suggests that prasugrel should be given only after >24 h with fibrin-specific thrombolytic agent and >48 h with fibrin nonspecific thrombolytic agents.^[23],[24] Hence, inherently prasugrel should not be given in adjunctive PCI. As prasugrel has better outcome during invasive strategy than clopidogrel, this may increase the difference between two groups even better, probably in favor of delayed routine PCI. However, the exact result with this hypothetical situation is not known and needs further study. In patients already loaded with clopidogrel, change over with prasugrel is not examined.

Overall, our study results raise need of more systematic quality data for status of PCI within 24 h as Class IIa indication in the ACC/AHA 2013 guidelines. We opine that this study should be considered as a pilot or preliminary observation and suggests a serious need for a randomized trial with adequate power of a study to draw a definite conclusion in this regard.

Study limitations

Since it is a single center, short follow-up, observational study, no definitive conclusion can be drawn. However, it can be viewed as hypothesis-generating study
Patients with age >75 years were excluded. This study did not consider stent thrombosis or previous stent implantation in patients. Further, patients with a history of coronary artery bypass grafting were not included in the study. Hence, the study results cannot be generalized and cannot be applied to these patient groups
Outcome of PCI depends to a great extent on experience of operators.

Conclusions

In our clinical setup where primary PCI is not readily available, pharmacoinvasive strategy is a valuable option, also since there is much delay in transfer to PCI-enabled center. The results of this study suggest that PCI done even after 24 h has comparable outcome to that of PCI within 24 h.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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