In low- and middle-income countries, timely primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) is often limited. When timely PPCI is not feasible, current guidelines recommend a pharmacoinvasive strategy with routine angiography and percutaneous coronary intervention (PCI), if indicated, within 3- 24 hours after fibrinolysis; however, the role of PCI beyond 24 hours remains uncertain. We compared clinical outcomes of PPCI versus extended pharmacoinvasive PCI (ePIPCI; PCI performed 3 to 48 hours after fibrinolysis) in STEMI. We analyzed the Madras Medical College STEMI Registry (September 2018 to October 2019), comparing patients undergoing PPCI with those receiving ePIPCI, including subgroups treated at 3 to 24 and 24 to 48 hours after fibrinolysis. Outcomes included in-hospital complications, in-hospital mortality, and 1-year all-cause mortality. Of the 2,499 STEMI patients enrolled, 248 underwent PPCI and 210 ePIPCI; among the remainder, 1,091 (43.7%) received fibrinolysis only, 825 (33.0%) had no revascularization, and 125 (5.0%) underwent delayed PCI. In-hospital complications (23.0% vs 21.5%; RR 1.05, 95% CI 0.75 to 1.48; p = 0.78), in-hospital mortality (4.4% vs 1.4%; RR 3.11, 95% CI 0.88 to 10.98; p = 0.07), and 1-year mortality (8.5% vs 7.4%; RR 1.14, 95% CI 0.59 to 2.19; p = 0.70) were similar between PPCI and ePIPCI. Outcomes were comparable between the 3 to 24-hour and 24 to 48-hour post-fibrinolysis subgroups. In multivariable analysis of the full cohort, index-hospitalization PCI was independently associated with lower in-hospital mortality (adjusted OR 0.36, 95% CI 0.21 to 0.62; p <0.001). In conclusion, PCI up to 48 hours after fibrinolysis yielded outcomes comparable to PPCI, supporting an extended pharmacoinvasive strategy in resource-limited settings.
Study Summary
What is known
In patients with ST-elevation myocardial infarction (STEMI), catheter-based therapies within a time window of 3 to 24 hours after fibrinolysis offer clinical benefit nearly equivalent to primary PCI.
Key question
In fibrinolysis-treated STEMI patients who subsequently undergo PCI, does extending the interval between fibrinolysis and PCI from the conventional 3 to 24 hours to a broader 3 to 48 hours window results in clinical outcomes comparable to those of primary PCI?
Key finding
In patients with STEMI who undergo fibrinolysis, PCI performed within 3 to 48 hours after fibrinolysis was associated with clinical outcomes comparable with primary PCI.
Clinical implication
Extending the PCI window to 3 to 48 hours after fibrinolysis may represent a pragmatic and safe revascularization strategy in settings with limited timely PCI access, thereby expanding access to catheter-based revascularization in resource-limited and geographically remote regions while maintaining outcomes comparable to primary PCI.
Cardiovascular disease is a major cause of mortality in India, with ST-elevation myocardial infarction (STEMI) representing the most common presentation of acute coronary syndrome. ,,, Timely primary percutaneous coronary intervention (PPCI) within 120 minutes is the preferred revascularization strategy. When delays to timely PPCI are anticipated, pharmacoinvasive therapy (PIT)- fibrinolysis followed by routine coronary angiography within 3 to 24 hours, with PCI if indicated-is recommended. ,, In low-and middle-income countries(LMIC), limited availability of PCI-capable centers, transport delays, financial constraints, and referral barriers, frequently prevent adherence to the recommended 3 to 24-hour pharmacoinvasive window in routine practice. ,
Although emerging evidence suggests that extending the pharmacoinvasive time window beyond 24 hours after fibrinolysis may preserve clinical benefits, its comparative effectiveness versus primary PCI has not been adequately evaluated in the real-world LMIC settings. Therefore, we aimed to compare clinical outcomes of primary PCI with an extended pharmacoinvasive PCI (ePIPCI) strategy (3 to 48 hours after fibrinolysis) in patients enrolled in the Madras Medical College STEMI (M-STEMI) Registry, a prospective registry in a public hospital in India. We also examined overall the revascularization pattern and outcome of the registry patients.
Methods
Study population, study site and data collection
The design and methodology of the Madras Medical College STEMI (M-STEMI) Registry study have been described previously. riefly, we prospectively enrolled consecutive patients presenting with STEMI within 48 hours of symptom onset, who sought care in our institution between September 2018 and October 2019. Data were collected in real time, using a standardized, STEMI registry case record, with predefined data fields, as described previously. This included time of symptom onset, time of decision to seek medical care, time of first medical contact, mode of transport to the hospital, baseline demographic characteristics, cardiovascular risk factors, comorbidities, clinical findings, and management details.
Fibrinolysis was the predominant reperfusion strategy during the study period. Primary and pharmacoinvasive PCI were offered predominantly during the regular office hours. Patients presenting outside the thrombolytic window or with contraindications to fibrinolysis were often unable to undergo definitive catheter-based revascularization, particularly when arriving outside routine working hours. Although many patients underwent coronary angiography, timely PCI was not always feasible because of coordination challenges between health insurance approval processes and treatment providers. Details regarding the use of various reperfusion modalities—including fibrinolysis and percutaneous coronary intervention (PCI)—were documented, along with any in-hospital complications such as mechanical, arrhythmic, or thromboembolic events.
Adjunctive pharmacotherapy and periprocedural care
All patients were discharged on guideline-directed medical therapy comprising aspirin 150 mg, clopidogrel 75 mg, and atorvastatin 80 mg, unless contraindicated. Beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers were prescribed as clinically indicated. Use of glycoprotein IIb/IIIa inhibitors, thrombus aspiration, vasopressors and mechanical ventilation was at the discretion of the treating physician.
Study definitions and clinical end points
STEMI was diagnosed based on characteristic chest pain and electrocardiographic ST-segment elevation in accordance with standard guidelines. Primary percutaneous coronary intervention (PPCI) was defined as coronary angiography and angioplasty (with or without stent implantation) of the culprit lesion within 12 to 24 hours’ time window in patients who have not received fibrinolysis. We defined extended pharmacoinvasive PCI (ePIPCI) as PCI performed between 3 to 48 hours after fibrinolysis. This group included both conventional pharmacoinvasive PCI (PIPCI), defined as PCI between 3 to 24 hours, and delayed pharmacoinvasive PCI (dPIPCI), defined as PCI between 24 to 48 hours following fibrinolysis. IRA patency was assessed using the Thrombolysis in Myocardial Infarction (TIMI) flow grading system. The IRA patency was defined as the presence of TIMI 2 or 3 flow.
Outcomes
The primary outcome of the study was in-hospital mortality. Secondary outcomes included in-hospital complications, cardiac hospitalizations during follow-up, and all-cause mortality at 1 year.
Discharge and follow-up
All patients were scheduled for follow-up at 1 year after discharge. However, follow-up for ∼75% of patients occurred during the COVID-19 pandemic, limiting in-person visits and ascertainment of nonfatal events. Thus, only all-cause mortality was reliably captured as the 1-year secondary outcome.
Analysis
We analyzed overall revascularization patterns and associated clinical outcomes. While all data were collected prospectively with prespecified analysis plans from the registry’s planning phase, analyses were performed later. Baseline characteristics and outcomes were compared between patients undergoing ePIPCI and PPCI. Categorical variables were summarized as frequencies and percentages and compared using Pearson’s Chi-squared test or Fisher’s exact test, as appropriate. Continuous variables were reported as means with standard deviations (SD) or medians with interquartile ranges (IQR), and compared using the Student’s t-test or Mann–Whitney U test based on data distribution. Variables with p <0.10 in univariable analysis were entered into multivariable logistic regression to identify independent predictors of in-hospital mortality. All statistical analyses were performed using SPSS version 2025 (IBM Corp., Armonk, NY), with a 2-sided p -value <0.05 considered statistically significant.
Results
Between September 2018 and October 2019, 2,499 adults with acute STEMI were enrolled in the M-STEMI registry (mean age 56.2 ± 12.3 years; range: 22 to 86). Women constituted 23% of the cohort. Most patients (75%; 1,874) presented in Killip class I; 51.7% (1,292) arrived within 6 hours of symptom onset, whereas 12.4% (309) presented beyond 24 hours. Baseline demographic and clinical characteristics are summarized in Table 1 and Figure 1 .
Table 1
Baseline features of the study cohort ( n = 2,499)
| Parameters | Baseline values |
|---|---|
| Age (years) | 56.2 ± 12.336 |
| Women | 582 (23.3%) |
| Risk factors/comorbidities | |
| Type II diabetes | 996 (39.9%) |
| Hypertension | 870 (34.8%) |
| Current smoking/tobacco use | 873 (34.9%) |
| Ex tobacco use | 167 (6.7%) |
| Prior coronary artery disease | 120 (4.8%) |
| Chronic kidney disease | 30 (1.2%) |
| Cerebrovascular accident | 50 (2%) |
| Time window from symptom onset (hours) | 13.3 ± 7.5 |
| Preinfarction angina | 1,526 (61.1%) |
| Myocardial infarction-location | |
| Anterior wall | 1,437 (57.5%) |
| Inferior wall | 982 (39.3%) |
| ECG findings | |
| Complete atrio-ventricular block | 88 (3.5%) |
| Right bundle branch block | 164 (6.6%) |
| Left bundle branch block | 11 (0.6%) |
| Ventricular tachycardia/fibrillation | 58 (2.3%) |
| Cardiogenic shock | 248 (9.9%) |
| Echocardiography | |
| Left ventricular systolic dysfunction (EF ≤40%) | 731 (29.3%) |
| Right ventricular dysfunction | 324 (17%) |
| Left ventricular thrombus | 33 (1.3%) |
| Ventricular septal rupture | 37 (1.5%) |
| Free wall rupture | 7 (0.3%) |
| Left ventricular ejection fraction (%) | 45.9 ± 18.8 |
| Tricuspid annular plane excursion (mm) | 17.8 ± 2.5 |
Baseline features of the patients enrolled.
Revascularization strategies used
Fibrinolysis was the dominant revascularization strategy, (52.1%; 1301/2499). Among those undergoing angiography 24 to 48 hours after fibrinolysis, TIMI 2/3 flow was present in 70% (145/210). Overall 23.3% (583/2499) of patients underwent PCI during the index hospitalization, including primary PCI in 9.9% (248), pharmacoinvasive PCI within 3 to 24 hours in 4.7% (118), and delayed pharmacoinvasive PCI at 24 to 48 hours in 3.7% (92); thus, 8.4% (210/2499) underwent extended pharmacoinvasive PCI (ePIPCI). Baseline characteristics according to the revascularization strategy are presented in the Table Supplementary Table . Older patients, women, individuals with hypertension, diabetes, admission Killip Class >1, LVEF <40%, or cardiogenic shock were less likely to undergo PCI.
Outcome
In-hospital mortality in the overall cohort was 11.3% (283/2499). Left ventricular systolic dysfunction (LVEF ≤40%) occurred in 29.3% (731) and Right ventricular dysfunction (TAPSE <17) in 17% (324) of patients. Overall in-hospital complications were observed in 34.4% (859) of the cohort.
Extended pharmacoinvasive PCI
We compared 248 patients undergoing primary PCI with 210 undergoing ePIPCI. Baseline demographic, clinical, echocardiographic characteristics and use of guideline-directed medical therapy were similar between groups ( Table 2 ). Compared with the primary PCI cohort, the ePIPCI group had higher preprocedure TIMI 2/3 flow rates (70% vs 21.4%; RR 2.62; 95% CI 2.11 to 3.27; p <0.001) and lower prevalence of left main or 3-vessel disease (1.4% vs 6.7%; RR 0.21, 95% CI 0.06 to 0.73; p = 0.008). In-hospital complications (23% vs 21.5%; RR 1.05; 95% CI 0.75 to 1.48; p = 0.78), in-hospital mortality (4.4% vs 1.4%; RR 3.11; 95% CI 0.88 to 10.98; p = 0.07), and 1-year mortality (8.5% vs 7.4%; RR 1.14; 95% CI 0.59 to 2.19; p = 0.70) were not significantly different between PPCI and ePIPCI ( Central Illustration ).
Table 2
Primary PCI versus extended pharmaco-invasive PCI–univariable analysis
| Parameters ( n = 458) | Total ( n = 458) | PPCI ( n = 248) | EPIPCI ( n = 210) | p value |
|---|---|---|---|---|
| Age | 53.37 ± 10.16 * | 52.98 ± 10.15 * | 53.83 ± 10.17 * | 0.373 |
| Female sex | 78 (17.0%) | 41 (16.5%) | 37 (17.6%) | 0.758 |
| Lower socioeconomic status | 449 (98.0%) | 241 (97.2%) | 208 (99.0%) | 0.151 |
| Cardio-vascular history | ||||
| Diabetes mellitus | 154 (33.6%) | 78 (31.5%) | 76 (36.2%) | 0.285 |
| Hypertension | 141 (30.8%) | 72 (29.0%) | 69 (32.9%) | 0.377 |
| Cerebrovascular accident | 8 (1.7%) | 5 (2.0%) | 3 (1.4%) | 0.632 |
| Past tobacco user | 36 (7.9%) | 14 (5.6%) | 22 (10.5%) | 0.056 |
| Current tobacco user | 190 (41.5%) | 107 (43.1%) | 83 (39.5%) | 0.433 |
| Prior CAD | 13 (2.8%) | 3 (1.4%) | 10 (4.0%) | 0.095 |
| Alcohol use | 175 (38.2%) | 91 (36.7%) | 84 (40.4%) | 0.468 |
| Sleep duration hours | 7.66 ± 0.81 | 7.73 ± 0.78 | 7.58 ± 0.84 | 0.044 |
| Alcohol use | 175 (38.2%) | 91 (36.7%) | 84 (40.4%) | 0.468 |
| Anterior myocardial infarction | 261 (57.0%) | 139 (56.0%) | 122 (58.1%) | 0.659 |
| Time to first medical contact | 6.03 ± 6.62 * | 5.51 ± 4.40 * | 6.64 ± 8.45 * | 0.082 |
| Killip class >1 | 61 (13.3%) | 27 (10.9%) | 34 (16.2%) | 0.160 |
| Right ventricular dysfunction | 45 (9.8%) | 23 (9.3%) | 22 (10.5%) | 0.667 |
| TAPSE | 18.07 ± 1.93 | 18.15 ± 1.73 | 17.98 ± 2.14 | 0.365 |
| LV ejection fraction (%) | 47.51 ± 7.56 * | 47.82 ± 7.30 * | 47.15 ± 7.83 * | 0.347 |
| Cardiac drugs use | ||||
| Clopidogrel | 454 (99.1%) | 247 (99.6%) | 207 (98.6%) | 0.337 |
| Aspirin | 452 (98.7%) | 245 (98.8%) | 207 (98.6%) | 0.837 |
| ACEI/ARB | 244 (53.3%) | 128 (51.6%) | 116 (55.2%) | 0.438 |
| Beta blocker | 328 (71.6%) | 174 (70.2%) | 154 (73.3%) | 0.453 |
| MRA | 119 (26.0%) | 61 (24.6%) | 58 (27.6%) | 0.462 |
| Pre-PCI TIMI 2/3 flow ( n = 436) | 194 (44.5%) | 49 (21.4%) | 145 (70%) | <0.001 |
| Single vessel disease | 351 (78.7%) | 178 (74.8%) | 173 (83.2%) | 0.031 |
| Single/two vessel disease | 427 (95.7%) | 222 (93.3%) | 205 (98.6%) | 0.008 |
| Complications | 103 (22.5%) | 57 (23.0%) | 46 (21.9%) | 0.783 |
| Arrhythmia | 97 (21.2%) | 54 (21.8%) | 43 (20.5%) | 0.735 |
| In hospital mortality | 14 (3.1%) | 11 (4.4%) | 3 (1.4%) | 0.063 |
| 1 year mortality ( n = 424) | 34 (8.0%) | 20 (8.5%) | 14 (7.4%) | 0.699 |
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