Exploring the Efficacy of Streptokinase and Tenecteplase: Comparing Thrombolytic, Pharmaco-Invasive Therapy and Primary PCI in ST-Elevated Myocardial Infarction Patients of Bangladesh

Objectives: The number of deaths from cardiovascular diseases (CVDs) is alarming, making them a major threat to global health. In low- and middle-income nations like Bangladesh, heart attacks and strokes are particularly common and cause the majority of these deaths. Data on ST-segment elevation myocardial infarction (STEMI) in Bangladesh is still scarce and rife with statistical errors, despite the country being among the most affected by CVD in South Asia. In order to fill this knowledge gap and provide guidance for the best possible management of STEMI, this study will compare and aggregate existing data on reperfusion strategies, such as thrombolysis, Primary Percutaneous Coronary Intervention (PPCI), and the Pharmaco-invasive (PI) strategy.

Methods: In primary healthcare settings, reperfusion techniques for ST-segment elevation myocardial infarction (STEMI) were assessed in this prospective observational study conducted in Bangladesh. We enrolled 599 patients, ages 18 to 75, who had STEMI symptoms within 6 hours. They received primary percutaneous coronary intervention (PCI) (C = 45), pharmaco-invasive therapy with streptokinase (A2 = 35) and tenecteplase (B2 = 49), or thrombolytic therapy with streptokinase (A1 = 271) or tenecteplase (B1 = 199). Laboratory tests, medical history, demographics, and treatment allocation data were gathered. ESC guidelines were followed by the in-hospital management. T-tests were used in the statistical analysis.

Results: Disparities in treatment outcomes were found when the study examined cardiovascular interventions in Bangladesh. Compared to group A1 (streptokinase), group B1 (tenecteplase) had greater success rates and fewer complications. Pharmaco-invasive methods, on the other hand, produced results that were comparable for A2 and B2. The revascularisation rates of the pharmaco-invasive groups varied, but group B1 showed noticeably fewer post-MI complications than group A1. Different groups had different mortality rates. A1 had a marginally higher mortality rate, but follow-up at 30 days revealed similar re-hospitalisation rates. This highlights the necessity of specialised interventions for the management of cardiovascular diseases, particularly in Bangladesh.

Conclusions: This study concludes that in order to effectively manage ST-segment elevation myocardial infarction (STEMI) in Bangladesh, tailored interventions are essential. When compared to streptokinase, the use of tenecteplase in thrombolytic therapy showed encouraging results, such as improved ST resolution, increased successful reperfusion, and a significant decrease in chest pain. Pharmaco-invasive techniques also produced similar outcomes. These results highlight the need for more research to improve STEMI treatment strategies in comparable settings, demonstrating a sense of urgency and concern for enhancing patient care in these environments.

Introduction

As the leading cause of death globally, cardiovascular diseases (CVDs) pose a serious threat to global health. A shocking 17.9 million deaths worldwide in 2019 were attributed to CVDs, accounting for 32% of all fatalities, according to a report issued by the World Health Organisation (WHO) on June 11, 2021. Heart attacks and strokes accounted for 85% of these fatalities. But the majority of these—three-quarters—occur in low- and middle-income nations [1].

An important epidemiological shift from communicable to non-communicable diseases (NCDs) has occurred in Bangladesh, a country in South Asia. Over the years, the leading causes of death in Bangladesh have also shifted from acute infectious and parasitic diseases to NCDs, with NCDs accounting for 59% of total deaths in 2014, compared to a mere 8% in 1986. Thus, CVD emerged as the most significant contributor to total mortality, representing 17% [2]–[4].

Interestingly, despite being a country with one of the highest rates of CVD in South Asia, Bangladesh remains relatively understudied in the global context, earning the label of a nation ‘missing in action’ [5]. Thus, data pertaining to ST-segment elevation myocardial infarction (STEMI) in Bangladesh is also insufficient, plagued by statistical flaws, and not readily accessible. Many smaller studies have been published in non-indexed national journals, but are often unavailable online and thus difficult to access. Recognising these limitations, the present registry has been conceived to compile available data on this critical public health issue, with the hope of serving as a crucial source of information.

Acute myocardial infarction is clinically characterised by symptoms of heart muscle ischemia, specific changes in the electrocardiogram (ECG), and the elevation of biomarkers indicating heart muscle damage [6]. In the management of STEMI, reperfusion therapy plays a pivotal role, and some form of reperfusion should be administered to all patients presenting within 12 hours of symptom onset.

The current global recommendations endorse three reperfusion strategies, namely Primary Percutaneous Coronary Intervention (PPCI), Thrombolysis, and the Pharmaco-invasive (PI) strategy. Primary PCI is acknowledged as the preferred reperfusion therapy, provided it can be executed within the recommended timeframe and by an experienced team. Thrombolysis serves as a crucial alternative, especially where PPCI is not feasible. In Bangladesh, thrombolysis employs agents such as streptokinase and tenecteplase, which is a widely practised form of reperfusion.

The PI strategy involves early thrombolysis followed by delayed within 3–24 hours’ coronary angiography and angioplasty. This approach targets patients presenting to non-PCI centres where PPCI cannot be completed within 120 minutes of chest pain. Thus, the strategy has also demonstrated good reperfusion and efficacy in reducing the rate of re-infarction [7].

In order to shed light on the efficacy and results of these reperfusion techniques, PPCI, thrombolysis (streptokinase and tenecteplase), and the pharmaco-invasive strategy, the current study compared them in the context of Bangladesh. In order to support well-informed clinical practice decision-making in these areas, we aim to add significant insights to the continuing discussion on the best STEMI management in low-resource economics through a thorough analysis.

Materials and Methods

Study Design and Patient Enrollment

In Bangladeshi primary healthcare facilities, the comparative, open-label, prospective observational study sought to evaluate the efficacy of reperfusion techniques for patients who presented with STEMI. Participants were considered for enrolment if they were adults (18–75 years old) with symptoms consistent with acute myocardial infarction and an ECG showing ST-segment elevation within 6 hours of chest pain. Prior myocardial infarction, posterior infarction, left bundle branch block, and other contraindications were among the conditions that were excluded. According to the investigator’s judgement, patients who satisfied the eligibility requirements were randomly assigned to either Primary Percutaneous Coronary Intervention (Group C), thrombolytic therapy with streptokinase and tenecteplase (Group A1 and B1, respectively), or pharmaco-invasive therapy with streptokinase or tenecteplase (Group A2 and B2, respectively).

Treatment Allocation

Based on clinical presentation and the clinician’s judgement, eligible patients were randomised to either a PCI strategy or a thrombolytic regimen after providing their informed consent. In the thrombolytic group, patients received either intravenous Streptokinase or tenecteplase, with simultaneous random assignment for pharmaco-invasive therapy. Streptokinase was administered as a 1.5-million-unit intravenous bolus infusion over 60 minutes, while tenecteplase dosage was determined based on the patient’s body weight. Patients within the thrombolytic groups were randomly assigned for pharmaco-invasive strategy based on the investigator’s discretion, considering Thrombolysis in Myocardial Infarction (TIMI) grade 0 or 1 flow.

Data Collection

Data was gathered from 15 centres in 5 different states of Bangladesh over the course of 5–6 months. The time it took for coronary angiograms (CAG) with or without intervention, time from symptom onset to hospital presentation, door-to-balloon time, door-to-needle time, and total ischemic time were meticulously documented. For patients undergoing thrombolysis, a 3- to 24-hour window period was considered for PCI, but in COVID-positive patients, up to 48 hours were allowed for the pharmaco-invasive procedure as extended pharmaco-invasive therapy.

Demographic, medical history at the baseline, and laboratory investigation details were documented in the three steps: baseline, discharge time, and follow-up after 30 days. Demographic details included age, gender, weight, Body mass- index (BMI), blood pressure, smoking status, and use of smokeless tobacco (paan, gutka) or other ways of tobacco consumption. Medical history covered aspects like ECG, stable angina, prior heart attack, PCI, family history of stroke/CVD, dyslipidemia, hypertension, and diabetes. The laboratory investigation details included various measures like ECG, RBCs, WBCs, Platelet count, Hemoglobin, Hematocrit, HbA1c, Total cholesterol, LDL, HDL, Triglycerides, Serum creatinine test, Blood urea nitrogen, eGFR and cardiac biomarkers (CPK, Ck-MB and Troponin).

In-Hospital Management

In-hospital management involved the use of dual antiplatelet therapy (aspirin + P2Y12 inhibitor). Clopidogrel was administered for a minimum of 1 month in patients treated with fibrinolysis without subsequent PCI.

Statistical Analysis

The study included a total of 603 participants. After excluding the data of 4 patients due to loss of follow-up, the analysis encompassed 599 patients. A T-test was utilised to compare the characteristics of patients across all groups. The analyses were performed using EXCEL version 2021.

Results

Out of the 599 patients, 470 recorded only thrombolysis and were categorised in group A1 (streptokinase), comprising 271 patients with an average age of 53.9 years, with 223 males, 46 females, and 2 patients of unspecified gender. In group B1 (tenecteplase), comprising 199 patients, the average age was 53.06 years, with 168 males, 27 females, and 4 patients of unspecified gender. Furthermore, out of 84 patients who underwent pharmacoinvasive treatment, 35 patients in group A2 underwent Pharmaco-invasive treatment with Streptokinase, having an average age of 51.15 years, including 32 males and 3 females. 49 patients in group B2 received Pharmaco-invasive treatment with tenecteplase, with an average age of 50.31 years, including 45 males and 4 females. Lastly, group C (Primary Percutaneous Coronary Intervention) consists of 45 patients, among which 41 were male, 3 were of unspecified gender, and 1 was female, with an average age of 52.85 years, as shown in Table I.

Table I. Baseline Characteristics of the Participants

Variables		Streptokinase	Tenecteplase	PCI	Pharmacoinvasive
					Streptokinase	Tenecteplase
Total subjects		271	199	45	35	49
Mean age		53.9	53.06	52.85	51.15	50.31
Sex	Male	223	168	41	32	45
	Female	46	27	1	3	4
	NA	2	4	3	0	0

Clinical Presentation

Thrombolysis

Upon collecting baseline data, it was observed that the incidence of heart failure and arrhythmia was significantly higher in patients belonging to group B1 (26.63% and 21.10%, respectively) compared to those in group A1 21.40% and 12.17%, respectively), with p-values of 0.0185 and <0.001, respectively. There was no noteworthy difference in the occurrence of shock among patients in any group. Additionally, the mean chest pain to balloon time was significantly higher in patients of group A1 (417.82 minutes) than in group B1 (306.4 minutes), with a p-value of 0.0139. Furthermore, the mean door-to-needle time for patients in Group A1 (116.75 minutes) was higher compared to that in Group B1 (63.24 minutes), with a p-value of 0.0251, as shown in Table II.

Table II. Clinical Presentation of the Participants

Variables	Strepto-kinase(n = 271)	Tenecteplase(n = 199)	p-value	PCI(n = 45)	Pharmacoinvasive
					Strepto-kinase(n = 35)	Pharmaco-invasive-SVs Strepto- kinase	Pharmaco- invasiveT Vs tenecteplase	PharmacoinvasiveS- Vs Pharmacoinvasive T	Tenecteplase(n= 49)
Heart failure (n)	58 (21.40%)	53 (26.63%)	0.0185	8 (17.8%)	5 (15.15%)	p = 0.3911	p = 0.0785	p = 0.9426	7 (14.58%)
Arrhythmia (n)	33 (12.17%)	42 (21.10%)	0.0090	8 (17.77%)	1 (3.030%)	p = 0.1062	p = 0.0881	p = 0.2036	5 (10.41%)
Shock (n)	34 (12.5%)	35 (17.58%)	0.127	5 (11.11%)	1 (3.030%)	p = 0.0979	p = 0.2229	p = 0.2036	5 (10.41%)
Chest pain duration (min)	407.82	306.4	0.0139	Chest pain to balloon time- 275.26	274.58	p = 0.0687	p = 0.1616	p = 0.0045	187.73
Door to needle time (min)	116.75	63.24	0.0251	Door to balloon time- 62.45	50.833	p = 0.2372	p = 0.0449	p = 0.167	38.39

Pharmaco-Invasive

No significant differences were observed in the clinical presentation of heart failure, arrhythmia, and shock between groups A2 and B2. Similarly, no notable distinctions were found in the mean door-to-balloon time across any of the groups. However, a significant difference was identified in the mean chest pain-to-balloon time between A2 (50.833 minutes) and B2 (38.39 minutes), with a p-value of 0.0045.

Percutaneous Coronary Intervention

Initially, in group C, 17% of patients presented with heart failure, 17.77% with arrhythmia, and 11.11% with shock at baseline. The mean chest pain to balloon time for this group was 275.26 minutes, while the mean door-to-needle time was 62.45 minutes.

Thrombolysis Immediate Outcome

Groups A1 and A2 (with success rates of 70.11% and 69.69%, respectively) exhibited significantly lower rates of successful reperfusion compared to groups B1 and B2 (with success rates of 81.9% and 81.25%, respectively), with a p-value of 0.0035 indicating a significant difference between A1 and B1.

The rate of ST resolutions in group B1 was notably higher at 80.40% compared to group A1, which had a rate of 70.11% (p = 0.0116). Conversely, within the pharmaco-invasive groups, A2 exhibited an ST resolution rate of 69.69%, while B2 demonstrated a higher rate of 83.33%.

The resolution of chest pain was observed in 81.90% of patients in group B1, compared to 67.89% in group A1 (p-value = 0.0006). In contrast, the rates were relatively similar in groups A2 and B2, with percentages of 84.84% and 83.33%, respectively.

The patients were promptly observed to experience allergic reactions and other medical issues, such as hypotension and bleeding, regardless of any notable differences among the various groups, as shown in Table III.

Table III. Thrombolysis Immediate Outcome of the Participants

Variables	Streptokinase (n = 271)	Tenecteplase(n = 199)	Tenecteplase Vs streptokinase	Pharmacoinvasive
				Strepto- kinase (n = 35)	Pharmaco-invasive- S Vs Streptokinase	Pharmaco- invasive T Vs Tenecteplase	Pharmaco- invasive S- Vs Pharmaco- invasive T	Tenecteplase(n = 49)
Successful reperfusion (n)	190 (70.11%)	163 (81.90%)	p = 0.0035	23 (69.69%)	p = 0.9593	p = 0.9161	p = 0.2212	39 (81.25%)
ST resolution (n)	190 (70.11%)	160 (80.40%)	p = 0.0116	23 (69.69%)	p = 0.9593	p = 0.6404	p = 0.1414	40 (83.33%)
Chest pain resolution (n)	184 (67.89%)	163 (81.90%)	p = 0.0006	28 (84.84%)	p = 0.0401	p = 0.8151	p = 0.8534	40 (83.33%)
Allergy (n)	6 (2.21%)	1 (0.5%)	p = 0.1305	0	p = 0.3752	p = 0.6206	–	0
Hypotension (n)	37 (13.65%)	39 (19.59%)	p = 0.0842	4 (12.11%)	p = 0.8020	p = 0.2501	p = 0.9575	6 (12.5%)
Bleeding (n)	5 (1.84%)	6 (3.01%)	p = 0.407	0	p = 0.4192	p = 0.7255	p = 0.3935	1 (2.08%)

In-Hospital Outcomes

Thrombolysis Groups

Post MI Angina and Emergency revascularisation were significantly lower in patients of group B1 (5.52% and 0%, respectively) as compared to group A1 (16.60% and 0.36%, respectively) with a p-value of 0.0003 and 0.0290, respectively. Several other im-hospital outcomes like major bleeding, re-infarction, LVF, arrhythmia, and stroke were all notably lower in group B1 (0.5%, 0.9632%, 0.8538%, 0.3199% and 1.50, respectively) as compared to A1 (0.73%, 2.58%, 21.4%, 9.22%, and 1.4%, respectively). There was no significant difference in the percentage of mortality between the two groups, with 8.11% in group A1 and 7.53% in group B1, as shown in Table IV.

Table IV. In-hospital Outcomes of the Participants

Variables	Streptokinase (n = 271)	Tenecte-plase(n = 199)	Tenecteplase Vs streptokinase	PCI	Pharmacoinvasive
					Strepto-kinase(n = 35)	Pharmaco- invasive S- vs streptokinase	Pharmacoinvasive T- vs Tenecteplase	Pharmacoinvasive S- Pharmacoinvasive	Tenecteplase (n = 49)
Major bleeding (n)	2 (0.73%)	1 (0.5%)	p = 0.7585	0	0	p = 0.6127	p = 0.6206	–	0
Post MI angina (n)	45 (16.60%)	11 (5.52%)	p = 0.0003	0	0	p = 0.0092	p = 0.3158	p = 0.3935	1 (2.08%)
Re- infarction (n)	7 (2.58%)	5 (2.51%)	p = 0.9632	0	0	p = 0.3372	p = 0.2635	–	0
LVF (n)	58 (21.40%)	44 (22.11%)	p = 0.8538	6 (13.33%)	4 (12.12%)	p = 0.2000	p = 0.0292	p = 0.5689	4 (8.33%)
Arrythmia (n)	25 (9.22%)	24 (12.06%)	p = 0.3199	3 (6.67%)	0	p = 0.0613	p = 0.4614	p = 0.0818	4 (8.33%)
Emergency (n) Revascularisation	1 (0.36%)	0	p = 0.0290	1 (2.22%)	3 (9.09%)	p < 0.0001	p = 0.0039	p = 0.3590	2 (4.166%)
Stroke (n)	4 (1.4%)	3 (1.5%)	p = 1.50	0	1 (3.03%)	p = 0.4684	p = 0.3894	p = 0.2229	0
Death (n)	22 (8.11%)	15 (7.53%)	p = 0.817	1 (2.22%)	2 (6.06%)	p = 0.6723	p = 0.0480	p = 0.0827	0

Pharmaco-Invasive Groups

No significant difference was observed between groups A2 and B2. However, post-myocardial infarction (MI) angina was notably lower in patients from the pharmaco-invasive group A2 (0%), in comparison to the thrombolysis group A1 (16.6%), with a p-value of 0.0092. Conversely, emergency revascularisation rates were significantly lower in patients from the thrombolysis groups, A1 (0.36%) and B1 (0%), when compared to those in the pharmaco-invasive groups, A2 (9.09%) and B2 (4.166%), with p-values of <0.0001 and 0.0039 for A1 vs A2 and B1 vs B2, respectively.

There was no noteworthy distinction in the percentage of mortality between the pharmaco-invasive groups (A2—6.06%; B2—0%). However, a substantial difference was observed in the percentage of mortality between group B1 (7.53%) and B2 (0%) with a p-value of 0.0480, as shown in Table IV.

PCI

Among all anticipated in-hospital outcomes, patients in group C encountered left ventricular failure (LVF) at a rate of 13.33%, arrhythmia at 6.67%, emergency revascularisation at 2.22%, and a mortality rate of 2.22% in Table IV.

Follow-Up

Upon a 30-day follow-up, re-hospitalisation rates were observed at 8.85%, 8.54%, 6.06%, 2.08%, and 2.22% for groups A1, B1, A2, B2, and C, respectively. Additionally, the mortality rates within the same timeframe were found to be 4.7%, 3.01%, 3.03%, 4.16%, and 2.22% for the corresponding groups A1, B1, A2, B2, and C, as shown in Table V.

Table V. Follow-up of the Participants

Variables	Strepto-kinase(n = 271)	Tenecteplase(n = 199)	PCI	Pharmacoinvasive
				Strepto-kinase (n = 35)	Pharmaco-invasive S- vs streptokinase	Pharmaco- invasive T- vs Tenecteplase	Pharmaco-invasive S- vs Pharmaco-invasive T	Tenecteplase(n = 49)
Re-Hospitalisation (n)	24 (8.85%)	17 (8.54%)	1 (2.22%)	2 (6.06%)	p = 0.5788	p = 0.1193	p = 0.3460	1 (2.08%)
		p = 0.9739
Death (n)	13 (4.7%)	6 (3.01%)	1 (2.22%)	1 (3.03%)	p = 0.6546	p = 0.6843	p = 0.7877	2 (4.16%)
		p = 0.332

Discussion

The present study provides valuable insights into the management of ST-segment elevation myocardial infarction (STEMI) in Bangladesh, a country facing a rising burden of cardiovascular diseases (CVDs) amidst epidemiological transitions. By comparing three reperfusion strategies (Primary Percutaneous Coronary Intervention (PPCI), Thrombolysis, and Pharmaco-invasive (PI) therapy), the study sheds light on their effectiveness and outcomes in a low-resource setting.

In comparison to pharmaco-invasive techniques and PPCI, thrombolysis—a type of reperfusion that is commonly used in Bangladesh—exhibited notable improvements in successful reperfusion rates, ST resolution, and the reduction of chest pain. Compared to thrombolysis with streptokinase (Group A1), the results indicate that thrombolysis with Tenecteplase (Group B1) is associated with a lower incidence of heart failure and arrhythmia [8]. Additionally, Group B1 showed a significant reduction in both door-to-needle time and chest pain to balloon time, suggesting that it may be better at managing acute myocardial infarction [9].

Pharmaco-invasive methods did not show differences in mean door-to-balloon time or heart failure, arrhythmia, or shock presentation between groups A2 and B2. However, there was a significant difference that favoured group B2 in the mean chest pain-to-balloon time [10], [11]. This highlights the potential benefits of the pharmaco-invasive approach, which calls for more research [12].

The complicated clinical profiles of patients undergoing percutaneous coronary intervention were highlighted by the rates of heart failure, arrhythmia, and shock observed in Group C. While the relatively short door-to-needle time indicates effective triage and intervention strategies, the prolonged chest pain-to-balloon time suggests possible delays in revascularisation [13].

The study’s conclusions showed that groups A and B had significantly different thrombolysis outcomes. In comparison to Group A, Group B continuously showed greater rates of successful reperfusion, ST resolution, and chest pain relief. Subgroup analysis revealed noteworthy differences in results between A1 and A2, as well as between B1 and B2, indicating possible variations in treatment response. Adverse events, however, were consistently noted in every group, emphasising the necessity of thorough risk assessment in thrombolytic therapy.

In treating acute myocardial infarction (MI), the study shows clinical differences between thrombolysis and pharmaco-invasive approaches. When thrombolysis was administered to Group B1, the rates of post-MI angina, emergency revascularisation, major bleeding, re-infarction, LVF, arrhythmia, and stroke were found to be significantly lower than those of Group A1. Comparable death rates indicate the effectiveness of thrombolysis. On the other hand, pharmaco-invasive methods (A2, B2) demonstrated similar results, while mortality was lower and post-MI angina and emergency revascularisation rates were higher. Notably, there was no mortality in Group B2. Further research was warranted after PCI (Group C) revealed alarming rates of mortality, emergency revascularisation, arrhythmia, and LVF. According to follow-up data, which show stable mortality trends and variable re-hospitalisation rates, post-discharge surveillance is crucial. In order to maximise results, customised treatment plans and all-encompassing post-MI care are recommended; this calls for more investigation into long-term effects and therapeutic improvements.

Conclusions

In order to effectively treat ST-segment elevation myocardial infarction (STEMI) in Bangladesh, this study emphasises the critical need for tailored interventions. Notably, when compared to streptokinase, the use of thrombolytic therapy with tenecteplase demonstrated encouraging outcomes, including increased ST resolution, improved reperfusion rates, and a notable decrease in chest pain. Pharmacoinvasive techniques showed similar efficacy. In light of the urgent need for better patient care, these findings highlight the necessity of additional research to refine STEMI treatment strategies in comparable settings. In order to reduce the burden of cardiovascular diseases and improve patient outcomes in Bangladesh, the study promotes tailored interventions that are in line with available resources.