Thrombolysis use in STEMI patients in Central Asia: lessons from the Bukhara region of Uzbekistan

Acute coronary syndrome (ACS) -including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTEMI) -remains one of the leading causes of death worldwide. According to the World Health Organization, cardiovascular diseases claim the lives of more than 17.9 million people each year, accounting for 32% of global deaths (1). Acute myocardial infarction occupies a special place in this, and if not treated promptly and effectively, it can have a mortality rate of up to 30% (2).Although primary percutaneous coronary intervention (PCI) is the gold standard for the treatment of STEMI in developed countries (3), fibrinolytic therapy remains the main reperfusion strategy in low-and middle-income countries due to the limited availability of PCI centers (4). However, global studies show that even fibrinolytic therapy is not sufficiently used in resourcelimited settings (5).Uzbekistan is characterized by a high prevalence of cardiovascular diseases. The country has a population of more than 35 million, most of whom live in rural areas, which makes access to specialized medical care difficult (6,36). In addition, the pre-hospital medical care system, including emergency medical services, is still in its infancy.In this article, we aimed to analyze the current state of treatment of patients with ACS in the Bukhara region of Uzbekistan, identify existing health system and policy barriers, and propose evidence-based policy recommendations. We argue that improving ACS outcomes requires not only clinical interventions but fundamental changes in health policy, governance structures, and resource allocation strategies.Central Asian countries, including Uzbekistan, face significant challenges in adapting their Soviet-era healthcare systems to modern requirements (7). Cardiovascular disease is the leading cause of death in the five Central Asian republics, with more than 1.5 million cases of acute and chronic cardiovascular disease reported annually in Uzbekistan (8). The cardiovascular system is largely organized around regional and district hospitals, with primary percutaneous coronary intervention (PCI) capabilities limited to specialized centers in large cities, and access to thrombolytic therapy remains limited in most institutions (8).There are 12 regions in Uzbekistan, most of which have very limited catheterization laboratories providing PCI services. According to the European Society of Cardiology (ESC) recommendations, primary PCI in STEMI patients should be performed within 120 minutes (9). However, due to geographical distances, inadequate transport infrastructure and limited ambulance capacity, achieving this time frame is almost impossible in rural areas (10).In addition, the ability to perform electrocardiography (ECG) and diagnose STEMI in the pre-hospital setting is limited. Many ambulance crews do not have a 12-lead ECG machine, which slows down early diagnosis and referral to the appropriate hospital (11).Fibrinolytic therapy remains the main reperfusion strategy for STEMI patients in settings where PCI is not possible (12). According to international recommendations, if primary PCI cannot be performed within 120 minutes, fibrinolytic therapy should be initiated within the first 12 hours, preferably within the first 30 minutes (9).However, the data indicate that fibrinolysis is not being used sufficiently. According to the data of the Bukhara Regional Health Department for November 2025, a total of 1070 ACS and 912 AMI patients were registered in the region (13). Of these, 278 patients had ACS with STelevation (STEMI), but only 86 patients (31.3%) received thrombolytic therapy. This is significantly lower than the 92.7% reperfusion rate (84.8-97.5%) reported across 29 countries in the 2021 European Society of Cardiology STEMI Registry (14). It is noteworthy that streptokinase is the only fibrinolytic agent used in all medical institutions in the region (13). However, current recommendations favor fibrin-specific agents such as tenecteplase or alteplase, as they are more effective and have fewer side effects (15). The use of streptokinase, although economically feasible, poses problems with the risk of allergic reactions and restrictions on repeated use (16).The analysis of the data shows that there are significant differences between urban and rural areas. In the branches of the major medical institutions in Bukhara, the Republican Specialized Scientific and Practical Medical Center of Cardiology (RISCMC) and the Republican Scientific Center of Emergency Medical Care (RSCEM), the use of thrombolysis was almost nonexistent (0%), although these centers admitted the largest number of STEMI patients (13). This situation can be explained by the availability of PCI in these centers or the strategy of timely referral of patients to PCI centers.Interestingly, the use of thrombolysis in rural areas is relatively high, averaging 34.2% ( 13). The highest rates were recorded in Jondor district (73.8%), Vobkent district (95.2%), which may indicate that some NSTEMI patients were also treated with thrombolysis. This difference is explained by the lack of access to PCI centers in rural areas and the fact that fibrinolytic therapy is the only reperfusion method. The overall mortality rate in the region was 6.3%, which is close to the 4-5% in-hospital mortality rate reported in modern registries in developed countries (17), although some districts (Bukhara district -10.5%, Gijduvan -10.2%, Peshku -9.8%) have significantly higher mortality rates (13). These differences may partly reflect inequalities in access to care. However, patient-level factors such as age, infarction location, comorbidities, and time to treatment may also contribute to the variation in observed mortality rates. The lack of patient-level data in our analysis limits our ability to determine the relative contribution of each factor.The reported thrombolysis rate in the Karakul District of 110%, meaning more patients received thrombolysis than were diagnosed with STEMI, requires thorough investigation, not just a cursory mention. This anomaly reveals fundamental problems in diagnosis, documentation, and protocol adherence that likely exist throughout the regional healthcare system.We investigated this finding through discussions with colleagues in the district and a review of available documentation. Several non-mutually exclusive explanations could explain this alarming statistic.First, misclassification of diagnoses is likely occurring. In our assessment, the most likely explanation is that some patients with NSTEMI or even unstable angina were misdiagnosed as STEMI and subsequently received thrombolysis. Physicians in community hospitals often lack access to serial troponin testing, and their ECG interpretation skills vary significantly. We have observed cases where nonspecific ST-T segment changes, left bundle branch block, or even early repolarization patterns were misinterpreted as ST-segment elevation myocardial infarction. Without cardiologist oversight and under pressure to "do something" for patients with chest pain, some physicians may prescribe thrombolysis based on clinical suspicion rather than clear ECG criteria.Second, documentation and reporting errors may contribute. The regional medical statistics system relies on manual reporting by district hospitals. We suspect that some institutions may underreport STEMI diagnoses while accurately reporting thrombolysis, creating an artificial discrepancy between the numerator and denominator. Alternatively, the diagnosis of patients initially classified as NSTEMI who subsequently developed STEMI (and who received thrombolysis) may not be updated in the reporting system. The lack of integrated electronic medical records makes accurate tracking extremely difficult.Third, protocol violations may be intentional. We must consider the troubling possibility that some physicians knowingly administer thrombolysis to patients with NSTEMI. This may be due to a misunderstanding of guidelines, the belief that "some treatment is better than no treatment", or pressure from patients or their families to pursue aggressive intervention. In resource-limited settings where PCI is unavailable, physicians may consider fibrinolysis the only available "active" treatment, even when guidelines recommend only medical therapy. This finding is not simply a statistical curiosity -it represents a patient safety concern. Thrombolysis in patients with NSTEMI is not recommended by any major guidelines because it does not improve outcomes and increases the risk of bleeding (33,34). The TACTICS-TIMI 18 trial and other landmark studies have shown that patients with NSTEMI benefit from early invasive strategies or medical therapy, not fibrinolysis.Providing thrombolysis to patients with STEMI exposes them to significant harm without the expected benefit:-0.5-1% risk of intracranial hemorrhage -potentially fatal or disabling -4-6% risk of major bleeding -requiring blood transfusion or intervention -No reduction in mortality -unlike STEMI, where timely thrombolysis saves lives -Potential delay in appropriate treatment for bleeding complications If even 10-20 patients with STEMI in the Karakul district receive inadequate thrombolysis, we can expect 1-2 cases of major bleeding and possibly one stroke or death directly related to this practice. These iatrogenic consequences are preventable.What does this say about the system as a whole?In our opinion, the Karakul anomaly is likely not unique -it is simply the most illustrative example of systemic problems existing throughout the region. Other districts with thrombolysis rates of 70-95% may also treat some STEMI patients, but not enough to exceed 100%. We hypothesize that inappropriate thrombolysis occurs throughout the system with varying frequency.This finding highlights several critical systemic failures:-Lack of diagnostic standards: There are no mandatory criteria for diagnosing STEMI before administering thrombolysis. -Lack of feedback: Physicians never know whether their diagnoses were correct.We urge the regional health department to conduct an urgent clinical audit of all thrombolysis cases in Karakul and other high-incidence districts. This audit should determine:-How many patients with STEMI or without ACS received thrombolysis? -What were the clinical outcomes, including bleeding complications?-What ECG findings informed the treatment decision? -Was a pretreatment consultation by a cardiologist provided?Based on the audit findings, immediate corrective actions should include:-Required ECG transmission to a regional cardiologist before any thrombolysis -A standardized STEMI diagnostic checklist that must be completed and documented -Real-time analysis of all thrombolysis cases within 24 hours -Feedback to physicians on diagnostic accuracy and outcomes -Refresher training programs for institutions with high rates of inappropriate treatmentWe emphasize that our goal is not to blame individual physicians who may be doing their best under difficult circumstances. Rather, we seek to highlight a systemic failure that puts both patients and physicians at risk. The Karakul anomaly should serve as an alarm signal for regional and national health authorities.There are a number of successful experiences in improving the care of patients with ACS in resource-limited countries. These experiences provide valuable lessons for Uzbekistan.As a country of over 1.4 billion people, mostly living in rural areas, India faced similar challenges to Uzbekistan (18). According to the CREATE registry, only 58.5% of STEMI patients in India received reperfusion therapy, with only 8.6% undergoing primary PCI (5).The STEMI network (TN-STEMI) established in 2010 in the state of Tamil Nadu has fundamentally changed this situation (19). The main principles of this program were as follows:First, a "hub-and-spoke" model was introduced -a network of several peripheral hospitals (spokes) was established around a central PCI center (hub). Patients diagnosed with STEMI in peripheral hospitals were immediately started on fibrinolytic therapy and then transferred to a PCI center (pharmaco-invasive strategy) (20).Second, a mobile ECG transmission system was introduced. ECG images obtained by ambulance crews were transmitted to the central hospital via smartphone and analyzed remotely by a cardiologist. This significantly reduced the time from "first medical contact to diagnosis" (21).Third, the drug tenecteplase was introduced. Compared to streptokinase, this drug is characterized by a single bolus injection, high fibrin specificity, and fewer hemorrhagic complications (22).As a result, in-hospital mortality decreased from 8.2% to 4.5%, and the percentage of patients receiving reperfusion increased from 60% to 92% in the program areas (20).Brazil is also a country that faces the challenges of a large geographical area and uneven health infrastructure. The Telemedicine Network (TNMG) implemented in the state of Minas Gerais covers more than 1,000 municipalities (23). In this system, ECGs performed in rural health centers are transmitted via the Internet to a central station, where they are analyzed and interpreted by a cardiologist within 10 minutes. 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