European Journal of Cardiovascular Medicine

Cardiovascular diseases (CVD) are the primary cause of mortality and disability globally, posing a significant health burden across all populations.^1,2 Myocardial Infarction (MI) is a life-threatening coronary event, often linked to sudden cardiac death (SCD), and represents the most severe form of coronary artery disease (CAD).^3,4 MI is classified into ST-elevation (STE-MI) and non-ST-elevation (NSTE-MI) types, along with unstable angina, is considered part of the acute coronary syndrome (ACS) spectrum.⁵  

India bears the world's highest burden of Acute Coronary Syndrome (ACS) cases. In India, over 450 million people live below the poverty line, prioritizing basic public health needs like nutrition, sanitation, and vaccination over acute treatments like STEMI reperfusion therapy. However, coronary artery disease (CAD) is a leading cause of death and disability, with prevalence rising dramatically, affecting 3–4% of rural and 8–10% of urban populations. CAD disproportionately impacts younger individuals, causing significant losses in productive years, with 18 million working years expected to be lost by 2030—nine times higher than in the U.S. Once seen as a disease of the wealthy, CAD now increasingly affects India’s poor and middle-class, posing severe implications for the nation's workforce and economy.^6-10

Timely reperfusion is crucial in STEMI patients. The choice between primary percutaneous coronary intervention (pPCI) and fibrinolytic therapy depends on treatment availability, delivery time, and total ischemic duration.¹¹ While pPCI is the guideline-preferred strategy, limited resources, infrastructure, and delays in low- to middle-income countries (LMICs) result in significantly lower access to reperfusion therapies.^12-14 Timely reperfusion within 12 hours of symptom onset is critical for improving survival in STEMI patients. Delays in achieving pPCI are common and linked to increased morbidity and mortality.^15,16

The pharmacoinvasive strategy involves immediate fibrinolysis followed by systematic coronary angiography, ideally within 3–24 hours post-fibrinolysis. This approach combines the accessibility of fibrinolytic therapy with the efficacy of percutaneous coronary angioplasty to reduce the risk of reinfarction and recurrent ischemia. By offering a practical solution for resource-limited settings, it enables timely initial treatment and enhances long-term outcomes through subsequent intervention.^17,18

This study evaluates the efficacy and safety of the pharmacoinvasive strategy compared to pPCI in STEMI patients during hospitalization.

OBJECTIVES: To compare the incidence of mortality, cardiogenic shock, and re-myocardial infarction between patients with acute myocardial infarction treated with pharmacoinvasive therapy and those treated with primary angioplasty.

Study design, sample size, source of data and method of data collection:

This was a prospective cross-sectional study carried out on 138 participants. The study group was divided into two groups, group 1 (patients who had primary PCI defined as PCI within 12 hours of symptom onset in a patient not receiving fibrinolysis for the infracted related artery as a reperfusion therapy) consisting of 69 patients and group 2 (Pharmacoinvasive PCI defined as Fibrinolysis followed by rescue or urgent PCI or by routine elective PCI (within 3 - 24 hours of fibrinolytic administration).

Inclusion criteria: The working diagnosis of STEMI was made based on symptoms such as persistent chest pain consistent with myocardial ischemia, along with an ECG showing ST-segment elevation (measured at the J point) with the following criteria: at least two contiguous leads with ST-segment elevation ≥ 2.5mm in men < 40 years, ≥ 2mm in men ≥ 40 years, or ≥ 1.5mm in women in leads V2–V3 and/or ≥ 1mm in the other leads, in the absence of left ventricular (LV) hypertrophy or left bundle branch block (LBBB).

Exclusion criteria: Late presentation (>12 hours from symptom onset to treatment) or unknown ischemic time, inability to obtain or interpret baseline ST-segment elevation, failure to administer acute reperfusion, baseline ECG showing left bundle branch block or paced rhythm, development of STEMI while the patient was admitted to the hospital for another reason, administration of fibrinolysis without subsequent cardiac catheterization, and a history of previous CABG.

All patients presenting with STEMI who fulfilled the inclusion and exclusion criteria and provided informed written consent were enrolled in the study. Baseline characteristics, including a detailed clinical assessment (age, sex, presenting symptoms, window period, traditional risk factors, vital parameters, Killip class, baseline ECG, bedside echocardiography, treatment intervals, reperfusion therapy, hospital management, and in-hospital clinical events), were collected. All the above data were recorded on a data sheet, and the variables were entered into a common database for analysis. Follow-up was conducted to assess the primary and secondary endpoints. All patients who were either referred from an outside centre after thrombolysis and underwent PCI, or who were initially thrombolysed in our centre and subsequently underwent coronary angiography with the intention of revascularizing the infarct-related artery, were included in the pharmacoinvasive therapy arm.

The study was carried out Department of Cardiology, Tirunelveli Medical College Hospital, Tirunelveli over period of one year from September 2023 to August 2024. Ethical committee approval was obtained from the Institutional Ethics Committee.

The PPCI group included STEMI patients who underwent coronary angiography, primary angioplasty, and intracoronary stent placement as the first reperfusion therapy within 12 hours of symptom onset. The pharmacoinvasive strategy (PIS) group included STEMI patients who received fibrinolysis within 12 hours of symptom onset, followed by coronary angiography and angioplasty within 3 - 24 hours if fibrinolysis was successful, or immediately if fibrinolysis failed. Patients who received no reperfusion treatment within the first 12 hours, those treated with fibrinolysis alone, or those with no reperfusion at any time were excluded from the analysis.

Statistical analysis:

The data collected was analysed using SPSS version 27.0 Socio-demographic variables were analysed in terms of mean, standard deviation (SD), frequency (n) and percentage (%). Independent t test/Mann Whitney U test was used to compare continuous variables between two groups depending on the normality of the data. Chi square test was used to compare categorical variables. A p-value of <0.05 was taken as statistically significant. Data results were represented in the form of tables and figures.

In this study the mean age in Group 1 (n=69) was 54.93 ± 10.247 years, while in Group 2 (n=69), it was 54.46 ± 9.393 years. The p-value for the comparison between the two groups was 0.782, indicating no significant difference in age between the groups. The mean of the study participants 41.7 + 8.32 years. Group 1 has a higher percentage of patients in the 41-50 years age range (33.3%) compared to Group 2 (20.3%). In contrast, Group 2 has a higher percentage of patients in the 51-60 years (39.1%) and 61-70 years (27.5%) age ranges compared to Group 1, which has 31.9% and 21.7%, respectively. In terms of gender distribution, Group 1 comprised 60 males (87%) and 9 females (13%), while Group 2 had 52 males (75.4%) and 17 females (24.6%). The p-value of 0.082 indicates that the gender distribution between the two groups is not statistically significant. (Table 1)

Table 1: Baseline characteristics of the study participants

Values are Mean + Standard deviation, n (%)

*Statistically significant at p<0.05

In terms of symptoms, both Group and Group 2 had a similar percentage of patients experiencing chest pain (97.1% in both groups). Shortness of breath was reported in 26.1% of Group 1 and 18.8% of Group 2, with a p-value of 0.308, suggesting no significant difference between the groups. Palpitations were more common in Group 2 (17.4%) compared to Group 1 (9.1%), but this difference was not statistically significant (p-value = 0.156). Giddiness was equally reported in both groups (7.7%), with a p-value of 1.0, showing no significant difference. However, syncope was reported in 4.3% of Group 2 and 0% of Group 1, and the p-value of 0.002 indicates a statistically significant difference between the two groups, suggesting that syncope occurred more frequently in Group 2. (Table 2)

Table 2: Symptomatology among study participants

 Values are n (%)

*Statistically significant at p<0.001

In terms of vital parameters, Group 1 had a mean pulse rate of 78.32 ± 12.398, while Group 2 had a mean pulse rate of 84.90 ± 13.022, with a p-value of 0.003, indicating a statistically significant difference between the two groups, suggesting that Group 2 had a higher pulse rate. The mean systolic blood pressure (SBP) for both groups was similar, with Group 1 having a mean of 125.07 ± 16.858 and Group 2 at 125.25 ± 29.189, and a p-value of 0.966, showing no significant difference. Similarly, for diastolic blood pressure (DBP), Group 1 had a mean of 76.52 ± 11.610, while Group 2 had 79.57 ± 9.917, with a p-value of 0.1, indicating no significant difference between the two groups. (Table 3)

Table 3: Vital parameters among study participants

 Values are Mean + Standard deviation

*Statistically significant at p<0.001

Group 1 had a mean "pain to door" time of 4.913 ± 0.935 minutes, while Group 2 had a mean of 6.022 ± 1.844 minutes, with a p-value of <0.0001, indicating a statistically significant difference, suggesting that patients in Group 1 reached the hospital faster than those in Group 2. Regarding "door to balloon" time, Group 1 had a mean of 56.52 ± 16.612 minutes, while Group 2 had a mean of 148.70 ± 32.080 minutes, with a p-value of <0.0001, indicating a significant difference. This suggests that Group 1 had a much quicker time to receive reperfusion therapy (balloon angioplasty) compared to Group 2. (Table 4)

Table 4: Transfer distance and time delays

 Values are Mean + Standard deviation

*Statistically significant at p<0.001

Table 5: Angiographic and echocardiography data among study participants

 Values are Mean + Standard deviation, n (%)

*Statistically significant at p<0.05

In lab investigations creatinine, urea, SGPT, and HDL levels showed significant differences, while other markers like hemoglobin, CK-MB, SGOT, sodium, potassium, triglycerides, and LDL were not significantly different between the two groups. (Table 6)

Table 6: Laboratory investigations

 Values are n (%)

*Statistically significant at p<0.05

The outcomes of the study showed no significant differences between Group 1 and Group 2 for acute kidney injury (AKI), with 15.9% of patients in Group 1 and 14.5% in Group 2 affected (p-value = 0.813). There was no significant difference in death rates, with no deaths in Group 1 and one death (1.4%) in Group 2 (p-value = 0.316). Reinfarction occurred in 5.8% of Group 1 patients and 1.4% of Group 2 patients, but the difference was not statistically significant (p-value = 0.172). The duration of stay was similar for both groups, with Group 1 having a mean of 6.61 ± 1.467 days and Group 2 having 6.49 ± 1.024 days (p-value = 0.591). However, the follow-up ejection fraction (EF) was significantly higher in Group 1 (51.07 ± 6.839%) compared to Group 2 (47.99 ± 6.328%) (p-value = 0.007). This suggests that Group 1 had better left ventricular function at follow-up. (Table 7)

Table 7: Patient outcome

Values are Mean + Standard deviation, n (%)

*Statistically significant at p<0.05

The pharmacoinvasive strategy involves initial fibrinolytic therapy to rapidly restore coronary blood flow, followed by early elective PCI to reopen the infarct-related artery. This approach is particularly relevant in settings where timely access to primary PCI centres is limited, making it a valuable strategy for prompt myocardial salvage. This study purpose is to evaluate the efficacy and safety of the pharmacoinvasive strategy in comparison to PPCI. The study will include all ST-elevation myocardial infarction (STEMI) patients admitted to the CPU and CCU over nine months, treated with either primary angioplasty or pharmacoinvasive therapy. It aims to evaluate primary endpoints—death, re-myocardial infarction, and cardiogenic shock—and secondary endpoints, including arrhythmias, bleeding complications, ischemic stroke, ejection fraction, mechanical complications, hospital stay duration, and post-infarction angina.

While fibrinolysis can be administered promptly, it carries risks of non-reperfusion and re-infarction. Combining it with timely PCI can mitigate these risks effectively.¹⁹ A large meta-analysis of seven trials demonstrated that early PCI following fibrinolysis significantly reduces the combined risk of death and re-infarction without notably increasing the risk of major bleeding or stroke. Although the studies primarily focused on rescue PCI rather than primary PCI, the findings emphasize the critical importance of timely reperfusion in managing acute coronary syndromes. This highlights the pharmacoinvasive strategy's potential to improve outcomes, particularly in settings where immediate access to primary PCI is unavailable.²⁰

As per the objective of this study, the results in our study suggested that on comparison between primary PCI and Group 2 pharmacoinvasive PCI shows no statistically significant difference in mortality (0% vs. 1.4%, p = 0.316). In a study by Rashid MK et al,²¹ in a comparison of outcomes between the pharmacoinvasive group (n = 236) and the primary PCI group (n = 980), the composite outcome of mortality, reinfarction, or stroke occurred in 6.4% and 7.0% of patients, respectively (p = 0.71), while mortality alone was 4.2% in the pharmacoinvasive group and 5.4% in the primary PCI group (p = 0.47). These differences were not statistically significant, indicating comparable outcomes between the two groups as that of our study. Similar results were found in a study by Dhar R, et al.,²² where there was no statistically significant difference in the mortality between two groups. The relatively low mortality rate observed in our study may be attributed to the smaller sample size and the variability in the populations studied. In contrast, other studies that reported higher mortality rates for acute coronary syndrome (ACS) included a broader range of ACS presentations, such as STEMI, NSTEMI, and unstable angina.

In outcome variable in our study, while there were no significant differences in AKI, reinfarction, or duration of stay between primary PCI and pharmacoinvasive PCI, the follow-up EF was significantly better in the primary PCI group. This suggests a potential benefit of primary PCI in preserving cardiac function post-procedure. In a study by Radwan HI et al²³ they compared three groups of patients with acute coronary syndrome (ACS)—Group I (50 patients receiving urgent percutaneous coronary intervention (PPCI) in a PPCI-capable center), Group II (50 patients transferred for PPCI from a non-PPCI-capable center), and Group III (50 patients treated with a pharmaco-invasive approach when PPCI could not be completed quickly)—the results showed no significant differences in reinfarction or cardiogenic shock incidence across the groups. The reinfarction rates were similar (1 in Group I, 2 in Group II, and 0 in Group III, p = 0.716), and cardiogenic shock occurred in 4.0% of Group I, 8.0% of Group II, and 6.0% of Group III (p = 0.992). In a study by Rashid MK et al,²¹ in a comparison between pharmacoinvasive PCI (n = 236) and primary PCI (n = 980), there were no significant differences in outcomes. The composite outcome of mortality, reinfarction, or stroke occurred in 6.4% of the pharmacoinvasive group and 7.0% of the primary PCI group (p = 0.71). Mortality was 4.2% in the pharmacoinvasive group and 5.4% in the primary PCI group (p = 0.47). Reinfarction occurred in 0.8% of the pharmacoinvasive group and 1.1% in the primary PCI group (p = 0.71). The length of stay at the cardiac center was the same median of 4 days for both groups (IQR 3–6), with no significant difference (p = 0.75). These results suggest that both approaches yielded similar outcomes in terms of mortality, reinfarction, stroke, and length of stay. In a study by Araiza-Garaygordobil D et al, on comparison between Primary PCI (n = 288) and the Pharmacoinvasive strategy (n = 291), there were no significant differences in the primary and secondary outcomes. The primary efficacy outcome, which includes cardiovascular death, cardiogenic shock, recurrent MI, or congestive heart failure, occurred in 14.5% of the primary PCI group and 11.3% of the pharmacoinvasive group (p = 0.24). For the components of the primary outcome, cardiovascular death occurred in 6.2% vs. 4.8% (p = 0.44), cardiogenic shock in 4.8% vs. 4.4% (p = 0.81), recurrent MI in 1.3% vs. 0.3% (p = 0.17), and congestive heart failure in 10.4% vs. 7.2% (p = 0.18). In terms of safety, major bleeding occurred in 5.9% vs. 5.1% (p = 0.69), and intracranial bleeding was observed in 0% vs. 0.6% (p = 0.15). These findings suggest similar efficacy and safety profiles between the two approaches.

In our study the pre and post TIMI score, in a comparison between Group 1 (patients who underwent primary PCI) and Group 2 (patients who underwent pharmacoinvasive PCI), notable differences were observed in pre-PCI TIMI scores. Group 1 had 10.1% of patients with a TIMI score of 0, while only 2.9% of Group 2 patients had a TIMI score of 0 (p = 0.039). Both groups had similar distributions for TIMI scores of 1 and 2, with 44.9% in Group 1 and 59.4% in Group 2 having a score of 1, and 44.9% in Group 1 and 44.9% in Group 2 having a score of 2. No patients in either group had a TIMI score of 3 before PCI. After PCI, Group 1 showed a 100% achievement of TIMI 3, while 97.1% of Group 2 patients achieved TIMI 3, with 2.9% having a TIMI score of 2 (p = 0.154). This indicates that both groups showed significant improvement post-PCI, with Group 1 having a slightly higher rate of achieving the highest TIMI score of 3. Thus, while Group 1 had a worse pre-PCI TIMI score, both groups had similar post-PCI outcomes, with a marginal advantage for Group 1 in achieving TIMI 3. In a study by Radwan HI et al,²³ comparing three management strategies for acute coronary syndrome, Group I (50 patients who received urgent percutaneous coronary intervention (PCI) in a PPCI-capable center), Group II (50 patients transferred for PPCI when presented to a non-PPCI capable center), and Group III (50 patients treated with a pharmaco-invasive approach when PPCI could not be completed quickly), differences in TIMI flow pre-PCI and post-PCI were observed. Group I and Group II had similar pre-PCI TIMI flow distributions, with 66% and 64% of patients having a TIMI flow of 1, respectively. In contrast, Group III had 78% of patients with a TIMI flow of 1, showing a better pre-PCI flow (p = 0.012). Post-PCI, Group III again showed superior results, with 84% achieving TIMI flow 3 compared to 82% in Group I and 70% in Group II (p = 0.009). These findings suggest that the pharmaco-invasive approach used in Group III resulted in better outcomes in both pre- and post-PCI TIMI flow compared to the other strategies. In a study by Rashid MK et al,²¹ In a comparison between Pharmacoinvasive PCI (n = 236) and Primary PCI (n = 980), differences in coronary flow at baseline and after the procedure were observed. At baseline, Pharmacoinvasive PCI patients had a higher proportion of TIMI grade 3 (57.7%) compared to Primary PCI patients (22.8%) (p < 0.0001). Conversely, Primary PCI patients had a greater proportion of TIMI grade 0 (57.8%) compared to Pharmacoinvasive PCI patients (25.5%). After the procedure, there was a slight difference in coronary flow, with 96.4% of Pharmacoinvasive PCI patients achieving TIMI grade 3, compared to 90.5% in Primary PCI patients (p = 0.07). However, Primary PCI patients had a higher incidence of TIMI grade 0 (4.5%) compared to Pharmacoinvasive PCI (1.4%). These results suggest that while both approaches show improvements in coronary flow, Pharmacoinvasive PCI may lead to a slightly higher rate of achieving the best coronary flow (TIMI grade 3). Similarly in a study by Sim DS, et al,²⁵ in a comparison between Pharmacoinvasive PCI (PI) (n = 708) and Primary PCI (PPCI) (n = 8878), pre-PCI TIMI flow grades showed significant differences (p < 0.001). PI patients had a higher proportion of TIMI grade 3 (50.6%) compared to PPCI patients (13.6%), while PPCI patients had a higher proportion of TIMI grade 0 (63.2%) compared to PI patients (17.8%). For TIMI grade 1 and 2, both groups had similar distributions. Post-PCI TIMI flow grades showed less pronounced differences. PI patients had 95.5% achieving TIMI grade 3, compared to 93.1% in PPCI patients (p = 0.267), with a very small proportion of patients in both groups having TIMI grades 0, 1, or 2 post-procedure. These results suggest that PI patients had better pre-PCI coronary flow but both groups showed similar post-PCI outcomes.

In our study in a comparison between Group 1 (patients who underwent primary PCI) and Group 2 (patients who underwent pharmacoinvasive PCI), Group 1 experienced significantly faster response times. The pain to door time was shorter in Group 1 (4.91 ± 0.94 minutes) compared to Group 2 (6.02 ± 1.84 minutes), with a p-value of <0.0001, indicating quicker initial medical attention for Group 1. Additionally, the door to balloon time was significantly shorter in Group 1 (56.52 ± 16.61 minutes) than in Group 2 (148.70 ± 32.08 minutes) (p < 0.0001), suggesting that PCI treatment was initiated much faster in Group 1. These results highlight the more rapid response in Group 1 patients, both from pain onset to hospital arrival and from hospital arrival to balloon inflation, compared to Group 2. In a study by Radwan HI et al,²³ angiographic data revealed that most patients in Groups I and II had a pre-PCI TIMI flow grade of 0 and 1, whereas Group III had a higher proportion of patients with pre-PCI TIMI flow grades of 2 and 3, with a significant difference between the groups (p = 0.012). Additionally, Group III showed a higher percentage of patients achieving a post-PCI TIMI flow grade of 3, with statistically significant differences observed between Group I and Group II (p = 0.009). These findings suggest that Group III had better pre- and post-PCI angiographic outcomes compared to Groups I and II. In a study by Sierra-Fragoso ÁA et al,²⁶ the door-to-balloon time was similar between the two groups, with the pharmacoinvasive group having a mean of 39 ± 20 minutes, and the primary PCI group having a mean of 39 ± 21 minutes. The p-value of 0.876 indicates no significant difference in door-to-balloon times between the two groups. In a study by Sim DS et al,²⁵ in a comparison between pharmacoinvasive PCI (PI) and primary PCI (PPCI) groups, the door-to-balloon time was significantly longer for the PI group compared to the PPCI group in both all patients and propensity-matched patients. For all patients, the PI group had a median door-to-balloon time of 40.1 hours (range 8.7–75.9), while the PPCI group had a median of 1.2 hours (range 0.9–1.7), with a p-value of <0.001. Similarly, in the propensity-matched cohort, the PI group had a median of 40.1 hours (range 8.7–75.8), while the PPCI group had a median of 1.3 hours (range 1.0–1.9), also with a p-value of <0.001. These findings indicate a substantial difference in door-to-balloon times between the two groups, with PPCI showing much faster treatment initiation.

Limitation: The primary limitation of this study is that it is not a randomized controlled trial, but rather a retrospective analysis using registry data. This design restricts the ability to establish causal relationships between the treatment strategies and patient outcomes, as it relies on previously collected data rather than random assignment of interventions. As a result, the findings may be influenced by biases and confounding factors inherent in the retrospective nature of the study. The sample size in this study was limited, and therefore, conducting research with a larger patient cohort is essential to draw more robust and reliable conclusions.

The pharmacoinvasive strategy can be a safe and effective alternative for patients who cannot achieve reperfusion within 120 minutes with primary PCI. There were no significant differences in primary and secondary outcomes, nor in treatment delays, including for those in the rescue PCI group. Given the study's limitations, there were no significant differences in in-hospital major cardiovascular events between STEMI patients receiving thrombolysis therapy, pharmacoinvasive PCI, and primary PCI.

ACKNOWLEDGEMENTS

DECLARATIONS

Funding:

Conflict of interest:

Ethical approval:

1. Jadhav UM. Cardio-metabolic disease in India-the up-coming tsunami. Ann Transl Med. 2018;6:295.
2. GBD compare | IHME Viz Hub. https://vizhub.healthdata.org/gbdcompare/. Accessed September 17, 2022.
3. Hahla MS, Saeed Y, Razieh H. Comparison of risk factors & clinical and angiographic characterization of STEMI in young adults with older patients. Res J Pharm Biol Chem Sci. 2016;7(6):2013–6.
4. Yeh RW, et al. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010;362(23):2155–65
5. Thygesen K, et al. Universal defnition of myocardial infarction. J Am Coll Cardiol. 2007;50(22):2173–95.
6. National Commission on Macroeconomics and Health. Burden of Disease in India. Delhi, India: Ministry of Health and Family Welfare, Government of India; 2005http://www.who. int/macrohealth/action/NCMH_Burden%20of%20disease(2% 20Sep%202005).pdf. Accessed 20.10.24.
7. Revised Poverty Estimates: What does this mean for India? http:// www.worldbank.org.in/WBSITE/EXTERNAL/COUNTRIES/ SOUTHASIAEXT/INDIAEXTN/0,con entMDK:21880804 wpagePK:141137wpiPK:141127wtheSitePK:295584,00.html Accessed 20.10.24.
8. Ghaffar A, Reddy KS, Singhi M. Burden of noncommunicable diseases in South Asia. BMJ. 2004;328: 807–810. Leeder S, Raymon
9. S, Greenberg H, et al. A Race Against Time: The Challenge of Cardiovascular Disease in Developing Economies. New York, USA: Columbia University; 2004 In: http://www. earthinstitute.columbia.edu/news/2004/images/Race against time_FINAL_051104.pdf. Accessed 20.11.24.
10. Jeemon P, Reddy KS. Social determinants of cardiovascular disease outcomes in Indians. Indian J Med Res. 2010;132:
11. 617–622.
12. Pinto DS, Kirtane AJ, Nallamothu BK, et al. Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reperfusion strategy. Circulation 2006;114:2019-25.
13. Ibáñez B, James E, Agewall, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119-77.
14. ACCESS Investigators. Management of acute coronary syndromes in developing countries: acute coronary events-a multinational survey of current management strategies. Am Heart J 2011;162:852-9.
15. Rosselló X, Huo Y, Pocock S, et al. Global geographical variations in ST segment elevation myocardial infarction management and post-discharge mortality. Int J Cardiol 2017;245:27-34.

• Bainey KR, Armstrong PW, Zheng Y, Brass N, Tyrrell BD, Leung R, et al. Pharmacoinvasive strategy versus primary percutaneous coronary intervention in ST-elevation myocardial infarction in clinical practice: insights from the Vital Heart Response Registry. Circ Cardiovasc Interv. 2019;12(10):e008059. https://doi.org/10.1161/CIRCINTERVENTIONS.119.008059.

17. 16. Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Danays T, Lambert Y, et al. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med. 2013;368(15):1379–87. https://doi.org/10.1056/ NEJMoa1301092.
18. Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Danays T, Lambert Y, et al. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med. 2013;368(15):1379-87.
19. Steg PG, Bonnefoy E, Chabaud S. Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty: data from the captim randomized clinical trial. ACC Curr J Rev. 2004;13(3):56-7
20. Berger PB, Ellis SG, Holmes DR Jr., et al. Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction: results from the global use of strategies to open occluded arteries in Acute Coronary Syndromes (GUSTO-IIb) trial. Circulation 1999;100:14–20
21. Borgia F, Goodman SG, Halvorsen S, et al. Early routine percutaneous coronary intervention after fibrinolysis vs. standard therapy in STsegment elevation myocardial infarction: a metaanalysis. Eur Heart J 2010;31:2156–69.
22. Rashid MK, Guron N, Bernick J, Wells GA, Blondeau M, Chong AY, et al. Safety and efficacy of a pharmacoinvasive strategy in ST-segment elevation myocardial infarction: a patient population study comparing a pharmacoinvasive strategy with a primary percutaneous coronary intervention strategy within a regional system. Cardiovascular Interventions. 2016 Oct 10;9(19):2014-20.
23. Dhar R, Momenuzzaman NA, Ahmed MU, Hossain S, Kumar DU, Shuvon AA. Evaluation of Pharmaco-invasive PCI in Terms of in Hospital Clinical Outcome of Acute Anterior ST Segment Elevation Myocardial Infarction Patients Compared to Primary PCI. Journal of Shaheed Suhrawardy Medical College. 2023;15(1):34-8.
24. Radwan HI, Deif MM, Frer AA, Mostafa TM, Mousa AS. Primary Angioplasty versus Pharmacoinvasive Strategy in Acute ST-Segment–Elevation Myocardial Infarction. The Egyptian Journal of Hospital Medicine. 2023 Jan 1;90(2):3147-55.
25. Araiza-Garaygordobil D, Gopar-Nieto R, Cabello-López A, Martinez-Amezcua P, Eid-Lidt G, Baeza-Herrera LA, et al. Pharmacoinvasive strategy vs primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: results from a study in Mexico city. CJC open. 2021 Apr 1;3(4):409-18.
26. Sim DS, Jeong MH, Ahn Y, Kim YJ, Chae SC, Hong TJ, et al. Pharmacoinvasive strategy versus primary percutaneous coronary intervention in patients with ST-segment–elevation myocardial infarction: a propensity score–matched analysis. Circulation: Cardiovascular Interventions. 2016 Sep;9(9):e003508.
27. Sierra-Fragoso ÁA, Galván-García JE, Vargas-Ramírez JF, Arboine-Aguirre LA, Muñoz-Consuegra CE, et al. Pharmacoinvasive strategy versus primary angioplasty in patients with acute ST-segment elevation myocardial infarction. Revista mexicana de cardiología. 2018 Sep;29(3):126-33.