A Retrospective Statistical Study of Cerebrovascular Stroke Cases in the Emergency Medical Service – Skopje, Republic of North Macedonia, 2021-2025

A Retrospective Statistical Study of Cerebrovascular Stroke Cases in the Emergency Medical Service – Skopje, Republic of North Macedonia, 2021-2025

Katerina Lazareva, Valentina Goricanec, Daniela Damjanovska Todorovska, Natalija Decovski

International Balkan University, Skopje, Vocational medical school, North Macedonia

ABSTRACT – Background: Stroke remains a significant global health problem and a major cause of mortality and long-term disability, disproportionately affecting low- and middle-income countries. In the Republic of North Macedonia, stroke represents a significant public health challenge, yet systematic data on prehospital stroke care are lacking. Aim: To conduct a comprehensive epidemiological analysis of stroke patients managed by the Emergency Medical Service in Skopje over a five-year period (2021 2025), including analysis of annual distribution, demographic characteristics, stroke types, and transport rates to hospital. Materials and Methods: This retrospective study analyzed data from the electronic database of the Emergency Medical Service Skopje, including all patients diagnosed with stroke during 20212025. Variables analyzed included total number of stroke-related calls, patient sex and age, stroke type (acute first-ever versus recurrent strokes), and transport to hospital. Descriptive statistics and chi- square tests were used for data analysis. Results: During the study period, 6,966 stroke cases were documented, accounting for 5.8% of all emergency calls. The greatest proportion occurred in 2021 (6.5%), whereas the smallest proportion was observed in 2024 (5.2%). Females were significantly more represented than males (57.7% vs. 42.4%; p < 0.001). Age analysis showed that 88.0% of patients were over 60 years, 11.8% were aged 4060 years, and only 0.27% were aged 2040 years. Acute (first-ever) strokes accounted for 61.5% of cases, while recurrent strokes (re-ictus) constituted 38.5%. A significant trend of increasing acute cases was observed, from 55.9% in 2021 to 70.9% in 2025 (p < 0.001). The transport rate to hospital showed a continuous improvement, increasing from 57.0% in 2021 to 72.6% in 2025 (p < 0.001), with an overall transport rate of 62.6%. Conclusion: This first comprehensive prehospital stroke study in Skopje reveals a predominant burden among the elderly, particularly women, with a concerning high proportion of recurrent strokes (38.5%) indicating suboptimal secondary prevention. The significant improvement in hospital transport rates over the five-year period (from 57.0% to 72.6%) reflects progress in prehospital care, education, and protocols. However, 37.4% of patients remain non-transported, highlighting an area for further improvement. These findings provide baseline data for the development of evidence-based protocols and targeted prevention strategies to reduce stroke-related morbidity and mortality in North Macedonia.

Keywords: stroke, cerebrovascular disease, epidemiology, prehospital care, emergency medical services, North Macedonia

INTRODUCTION

Cerebrovascular stroke is widely recognized as the number one cause of global mortality and disability and continues to pose a serious challenge to healthcare systems worldwide. Although significant progress has been made in prevention and therapeutic approaches, the overall public health burden of stroke remains significant. Data from the 2021 GBDS indicate that approximately

93.8 million people worldwide have lived with stroke, with an estimated 11.9 million new cases and approximately 7.3 million deaths occurring each year. These data place stroke as the second leading cause of death and the third leading cause of combined death and disability worldwide [1]. The distribution is not equal across regions. More than two-thirds of stroke-related deaths occur in low- and middle-income countries, where healthcare resources, prevention programs, and access to specialized treatment are often limited [1]. This disparity highlights the need for improved public health strategies, early recognition of symptoms, and efficient EMS.

In the Republic of North Macedonia, cerebrovascular diseases represent a similarly significant health problem. A regional epidemiological study conducted in the Strumica area and extrapolated to the national level reported a morbidity rate of cerebral infarction of 14.7 per 10,000 inhabitants, with the highest incidence observed among individuals aged 6574 years [2]. Additional hospital-based data from the Clinical Hospital in Tetovo for the period between January 2022 and January 2023 indicated that ischemic stroke accounted for 81.95% of stroke hospitalizations, while hemorrhagic stroke represented 18.05% of cases [3]. Studies

evaluating public awareness of stroke risk factors in the southwestern region of the country have shown that hypertension is the most commonly recognized risk factor (38%), followed by smoking (17%) and stress (15%) [4]. Furthermore, investigations addressing specific stroke mechanisms, including cryptogenic stroke associated with right-to-left shunt in patients older than 60 years, demonstrate the complex and multifactorial nature of cerebrovascular diseases within the national population [5]. Timely intervention is a key factor in outcomes, as therapeutic treatment such as intravenous thrombolysis and mechanical thrombectomy is limited.During an untreated ischemic stroke, a large number of neurons are estimated to be lost every minute. Consequently, rapid identification and management are essential. Emergency medical services represent the first and often the most crucial point of contact for patients experiencing symptoms of acute stroke. Their ability to recognize stroke in the prehospital setting, perform an initial clinical assessment, and ensure rapid transport to a hospital can significantly influence access to time-sensitive therapies. The Emergency Medical Service in Skopje serves as the primary provider of prehospital care for the capital city and surrounding areas and manages a substantial number of neurological emergencies each year. However, despite the recognized importance of prehospital stroke management, there remains a limited amount of systematic data regarding the epidemiological characteristics and clinical presentation of stroke patients treated by emergency services in North Macedonia.

This retrospective statistical study aims to examine cases of cerebrovascular stroke managed by the Emergency Medical Service in Skopje over a five-year period, from 2021 to 2025.By examining demographic characteristics, clinical presentation, temporal distribution, and aspects of prehospital management, the aim of this study is to provide a clearer understanding of the burden of stroke faced by emergency services in the capital. The findings may contribute to improving prehospital protocols, optimizing resource allocation, and supporting the development of evidence-based strategies for stroke care in North Macedonia.

BACKGROUND

Cerebrovascular stroke is a global health challenge with significant morbidity, mortality, and socioeconomic consequences. According to the Global Burden of Disease 2021 study, stroke affected approximately 93.8 million people worldwide, with 11.9 million new cases and 7.3 million deaths annually, positioning it as the second leading cause of death and the third leading cause of combined death and disability globally [1]. The epidemiological transition observed in recent decades has resulted in a disproportionate burden on low- and middle-income countries, which account for over two-thirds of all stroke-related deaths [1]. This disparity underscores the urgent need for region-pecific epidemiological data and tailored healthcare interventions.

Global Perspectives on Prehospital Stroke Management

The critical importance of timely intervention in acute stroke care has been firmly established in the medical literature. The therapeutic window for intravenous thrombolysis and mechanical thrombectomy remains extremely narrow, with each minute of delayed treatment resulting in the irreversible loss of approximately 1.9 million neurons, 13.8 billion synapses, and 12 kilometers of axonal fibers [6]. This neurobiological reality necessitates the development of efficient stroke systems of care that prioritize rapid recognition, transport, and treatment.

The 2026 Guideline for the Early Management of Patients with Acute Ischemic Stroke, published by the AHA and the ASA, represents the current reference standard for evidence-based stroke management [6]. This updated document supersedes the 2018 recommendations and integrates recent evidence related to thrombolytic therapy, patient selection for endovascular thrombectomy, as well as the management of conditions such as hyperglycemia and dysphagia in acute stroke care [7]. It recommends the use of standardized prehospital stroke assessment scales, prioritization of emergency dispatch, early notification of the receiving hospital, and rapid transport to the nearest stroke-capable center [6][7].

In addition to these American recommendations, the EAN together with the European Stroke Organisation has issued a consensus statement and practical guidance addressing the prehospital management of stroke [8]. Although the level of evidence for specific interventions remains limited, European experts strongly emphasize the importance of public education campaigns aimed at increasing awareness of stroke symptoms and encouraging prompt activation of emergency medical services. Good-quality evidence supports training emergency medical personnel in stroke symptom recognition and implementation of pre-hospital stroke code protocols [8]. However, there is insufficient evidence to recommend the routine use of mobile stroke units that deliver intravenous thrombolysis at the scene, and recommendations for pre-hospital telemedicine during ambulance transport cannot be made due to limited feasibility studies [8].

Stroke Epidemiology in the Republic of North Macedonia

In the Republic of North Macedonia, cerebrovascular diseases constitute a significant public health burden, though comprehensive national epidemiological data remain limited. A retrospective analysis of patients with cerebral infarction from the Strumica region, conducted between 2015 and 2020, provides valuable insights into the regional stroke epidemiology [2]. The study, which included

1,132 patients, revealed that the majority of hospitalizations occurred in the 65-74 years age group (35.0%), with males demonstrating higher risk (57.6% of cases). The average age at hospitalization was 68 years (66.8 for males, 69 for females). The average morbidity rate per 10,000 inhabitants was 14.3 in the Strumica region and 14.7 at the national level, with a continuous decrease in hospitalized patients from 2016 to 2020, culminating in a 50% reduction in 2020 compared to 2016 [2]. The incidence of stroke demonstrated a clear age-dependent pattern, reaching its peak in the seventh and eighth decades of life [2][9]. A hospital- based study conducted at the Clinical Hospital Tetovo between January 2022 and January 2023 provides additional clinical data on stroke presentation and outcomes [3]. Among 286 hospitalized patients (152 males, 134 females), acute strokes constituted 71.68% of all neurological admissions, followed by transient ischemic attacks (3.49%) and other cerebrovascular diseases (4.89%). Acute ischemic stroke (AIS) was the predominant stroke subtype, accounting for 81.95% of stroke hospitalizations, while acute hemorrhagic stroke (AHS) comprised 18.05% [3][10]. The study documented a mortality rate of 18.54%, with an additional 6.34% of patients discharged in serious health condition. Notably, only two thrombolysis procedures were performed during the study period due to limited patient eligibility, highlighting potential gaps in acute stroke treatment availability [3]. The investigators concluded that AIS occurs more frequently in elderly patients with cardiovascular comorbidities, and that aging, comorbidities, acute stroke severity, and impaired consciousness on admission contribute significantly to fatal outcomes [3][10]. Public awareness of stroke represents a critical determinant of prehospital delay and treatment seeking behavior. A cross-sectional study conducted in the Southwestern region of North Macedonia between March 2019 and April 2021 assessed community knowledge of stroke symptoms, risk factors, and information sources among 576 respondents aged 18 years and older [4]. Stress (15%), dyslipidemia (13%), hypertension (38%), and smoking (17%) were the most commonly identified risk factors for stroke. Nevertheless, a considerable proportion of respondents lacked knowledge in this area, with 44% unable to name any risk factor and 46% reporting that they did not know how to recognize stroke symptoms. Among participants who were able to identify warning signs, unilateral paralysis was the most commonly mentioned (29%), followed by speech disturbances (22%) and facial paralysis (14%). The internet was reported as the main source of information about stroke, cited by 42% of respondents. Self-reported prevalence of risk factors revealed that 42% had hypertension, 33% had elevated triglycerides, 25% consumed alcohol weekly, and 20% were physically inactive [4]. These findings underscore the urgent need for community-based education programs to increase public knowledge of stroke, with internet and television identified as potentially powerful educational tools [4]. Additional research has explored specific stroke subtypes in the Macedonian population. A study on right to left shunt and cryptogenic stroke in patients over 60 years old demonstrated the complexity of cerebrovascular pathology and the importance of advanced diagnostic approaches in understanding stroke etiology, particularly in older adults [5].

Research Gap and Rationale for the Current Study

Despite the existence of hospital-based studies from specific regions of North Macedonia [25], there remains a significant gap in understanding the prehospital phase of stroke care. The Emergency Medical Service in Skopje, as the primary prehospital care provider for the capital city and surrounding regions, manages a substantial volume of neurological emergencies annually. However, no comprehensive analysis has been conducted to characterize the demographic patterns, clinical presentations, temporal distributions, and prehospital management strategies for stroke patients encountered by emergency services in Skopje. This lack of systematic data impedes evidence-based protocol development, resource allocation, and quality improvement initiatives in prehospital stroke care.

The present study addresses this critical gap by providing the first comprehensive retrospective analysis of cerebrovascular stroke cases managed by the Emergency Medical Service in Skopje over a five-year period (2021-2025). By examining demographic characteristics, clinical presentation, timing, and aspects of prehospital management, this study provides a clearer understanding of the burden of stroke faced by emergency services in the capital.The findings will inform the development of tailored prehospital protocols, identify areas for system improvement, and contribute to the broader goal of reducing stroke-related morbidity and mortality in the Republic of North Macedonia.

AIM OF THE STUDY

The primary objective of this study is to conduct a comprehensive epidemiological analysis of stroke patients managed by the Emergency Medical Service in Skopje over the five-year period from 2021 to 2025.

The specific aims include:

Quantifying the workload Determining the total number of stroke-elated emergency calls and prehospital interventions, thereby establishing the volume of acute cerebrovascular pathology encountered by the service.

Differentiating stroke types Distinguishing between first-ever (incident) strokes and recurrent events (re-ictus) or chronic sequelae of previous cerebrovascular insults, enabling characterization of disease dynamics within the study period.

Demographic profiling Analyzing the age and sex distribution of affected individuals to identify the most vulnerable population segments and provide targeted epidemiological insight into stroke burden in the capital region.

Evaluating prehospital timeliness Assessing the proportion of patients immediately transported to hospital as a surrogate marker for the timeliness of emergency response and its potential impact on acute stroke outcomes, including eligibility for reperfusion therapies and functional prognosis.

By addressing these aims, the study will generate essential baseline data on prehospital stroke care in Skopje, inform evidence- based protocol development, and contribute to reducing stroke-related morbidity and mortality in the Republic of North Macedonia.

MATERIALS AND METHODS

Study Design

This research constitutes a retrospective epidemiological study conducted using data from the emergency medical service in Skopje, Republic of North Macedonia. The study covers a five-year period, from 2021 to 2025.

Data Source

Data for the study were extracted from the electronic database of the Emergency Medical Service Skopje. This database systematically records all emergency calls and field interventions, including demographic and clinical characteristics of patients, diagnoses, and undertaken procedures.

Study Population

The study population includes all patients diagnosed with stroke who were recorded in the emergency medical service during the 20212025 period. No selective sampling was applied, thus encompassing all cases from the real-world population that sought emergency medical assistance during the analyzed period. This approach ensures high external validity of the results and representativeness of the conclusions.

Variables Analyzed

The following variables were analyzed in the study:

Total number of emergency calls to the emergency medical service by year, Number of stroke patients (absolute values and proportions), Stroke type: differentiation between acute first-ever cases and recurrent strokes (re-ictus), Demographic characteristics: patient sex and age, Intervention outcome: assessment of the proportion of patients transported to the nearest hospital, as an indicator of prehospital care timeliness and potential access to further hospital therapy

Statistical Analysis

The following statistical methods were applied for data processing and analysis:

Descriptive statistics: Data are presented as absolute numbers and percentages (%) to illustrate the relative frequency of different categories (distribution by year, sex, age groups, stroke type, and hospital transport).

Chi-square test (² test): Applied to compare proportions between different categories, in order to determine the existence of

statistically significant differences in:

Stroke distribution across the analyzed years, Incidence between males and females, Frequency among different age groups, Distribution between first-ever and recurrent strokes

When a statistically significant difference was identified, additional analysis was conducted to determine which category contributed most to the observed difference (post-hoc analysis).

Data were processed using statistical software, with p-values < 0.05 considered statistically significant.

Ethical Considerations

The study was conducted in accordance with ethical principles for medical research. Data were analyzed anonymously, without the possibility of identifying individual patients, thereby ensuring confidentiality of personal information.

RESULTS

1. Total Volume and Annual Distribution of Stroke Cases

   During the 20212025 period, the Emergency Medical Service Skopje recorded a total of 119,946 calls, of which 6,966 (5.8%) were stroke-related. The annual distribution of calls and stroke cases is presented in Table 1.

   Table 1. Total EMS Calls and Stroke Cases by Year (20212025)

   Year	Total Calls (n)	Stroke Cases (n)	Proportion (%)
   2021	22,864	1,489	6.5
   2022	24,273	1,428	5.9
   2023	24,104	1,469	6.1
   2024	25,198	1,301	5.2
   2025	23,507	1,279	5.4
   Total	119,946	6,966	5.8

   The highest relative proportion of stroke cases in the total service activity was observed in 2021 (6.5%), and the lowest in 2024 (5.2%). Statistical analysis showed a significant difference in proportions across the years (² = 18.27; p < 0.001), with the greatest contribution from 2021.

2. Sex Distribution of Patients

   Of the total 6,966 patients, 2,952 (42.4%) were male and 4,024 (57.7%) were female. The annual sex distribution is presented in Table 2.

   Table 2. Distribution of Stroke Patients by Sex and Year (20212025)

   Year	Total	Males (n)	Males (%)	Females (n)	Females (%)
   2021	1,489	635	42.6	854	57.4
   2022	1,428	610	42.7	818	57.3
   2023	1,469	622	42.3	847	57.7
   2024	1,301	542	41.7	759	58.3
   2025	1,279	543	42.5	736	57.5
   Total	6,966	2,952	42.4	4,024	57.7

   The difference between sexes is highly statistically significant (² = 84.62; p < 0.001). Females were consistently more represented in all years, with the most pronounced difference in 2024 (58.3% vs. 41.7%).

3. Age Distribution of Patients

   Age analysis showed that stroke is predominantly a disease of the elderly population. Of the total 6,966 cases, 6,128 (88.0%) were aged over 60 years, 819 (11.8%) in the 4060 age group, and only 19 (0.27%) in the 2040 age group. The detailed annual distribution is presented in Table 3.

   Table 3. Age Distribution of Stroke Patients by Year (20212025)

   Year	Total	2040 y (n)	2040 y (%)	4060 y (n)	4060 y (%)	>60 y (n)	>60 y (%)
   2021	1,489	3	0.20	172	11.55	1,314	88.3
   2022	1,428	4	0.28	172	12.05	1,252	87.7
   2023	1,469	1	0.07	162	11.03	1,306	88.9
   2024	1,301	4	0.31	163	12.53	1,134	87.2
   2025	1,279	7	0.55	150	11.73	1,122	87.7
   Total	6,966	19	0.27	819	11.8	6,128	88.0

   The difference between age groups is highly statistically significant (² = 1,842.3; p < 0.001). The largest contribution comes from the over 60 age group (94.2% of the total ² value). A slight increase in cases among young adults (2040 years) was observed in 2025 (0.55%).

4. Stroke Type Acute vs. Recurrent (re-ictus)

   During the entire period, 4,284 cases (61.5%) were classified as acute (first-ever) strokes, while 2,682 (38.5%) were recurrent strokes. The annual distribution is presented in Table 4.

   Table 4. Distribution of Acute and Recurrent Stroke Cases by Year (20212025)

   Year	Total	Acute (n)	Acute (%)	Recurrent (n)	Recurrent (%)
   2021	1,489	833	55.9	656	44.1
   2022	1,428	872	61.1	556	38.9
   2023	1,469	845	57.6	624	42.4
   2024	1,301	828	63.6	473	36.4
   2025	1,279	906	70.9	373	29.1
   Total	6,966	4,284	61.5	2,682	38.5

   A continuous increase in the proportion of acute cases is evident from 55.9% in 2021 to 70.9% in 2025. Conversely, the proportion of recurrent cases decreased from 44.1% to 29.1%. The chi-square test confirms that the differences across years are highly significant (² = 78.43; p < 0.001), with the greatest contribution from 2025 (60.0%).

5. Patient Transport to Hospital

Of the total 6,966 patients, 4,361 (62.6%) were transported to the nearest neurology clinic, while 2,605 (37.4%) remained and were treated at home. Annual transport rates are presented in Table 5.

Table 5. Patient Transport to Hospital by Year (20212025)

The transport rate shows a continuous increase from 57.0% in 2021 to 72.6% in 2025. The differences across years are statistically significant (² = 32.22; p < 0.001), with the greatest contribution from 2025 (63.6%). Simultaneously, the proportion of non- transported patients decreased, indicating improvement in prehospital care.

DISCUSSION

This study represents the first comprehensive retrospective analysis of stroke cases managed by an emergency medical service in the Republic of North Macedonia. The findings provide significant insights into the epidemiology, demographic characteristics, and prehospital care of patients with cerebrovascular incidents in the urban setting of Skopje, and their comparison with global trends enables deeper interpretation and identification of areas for improvement.

Global Epidemiological Perspective

The latest data from the Global Burden of Disease Study 2021, the global number of incident strokes increased by 70.2% in the period 19902021, reaching 11.9 million new cases annually, while the total number of deaths increased by 32.17% to 7.3 million [1, 2]. This increase, as shown by the study of Yang et al., is primarily due to population aging (45.3%) and population growth (29.1%) [2]. Simultaneously, age-standardized incidence and mortality rates have decreased by 21.78% and 39.10% respectively, indicating improvements in healthcare and risk factor control [2][3]. This divergence between absolute numbers and age- standardized rates is consistent with our findings in Skopje, where the absolute number of cases remains high despite annual fluctuations. The WHO and the WSO in their Global Fact Sheet for 2025 emphasize that stroke remains the second leading cause of death and the third leading cause of combined death and disability worldwide, with estimated annual costs exceeding 890 billion US dollars (0.66% of global GDP) [4]. Particularly concerning is the fact that 87% of deaths and 89% of DALYs are concentrated in lower-income countries, a category that includes North Macedonia. This disproportion confirms the importance of our study and the need for region-specific epidemiological data.

Demographic Characteristics in a Global Context

Age Distribution: The predominant representation of the elderly population (88.0% over 60 years) in our sample is consistent with global epidemiological data. The study by Qian et al. shows that population aging is the dominant factor in the increasing burden of stroke, especially in regions with medium and low socio-demographic index [3]. However, global trends indicate a "double burden" a simultaneous increase in incidence among the elderly and a rise in cases among the young population [5]. Our data show a slight increase in cases in the 2040 age group in 2025 (0.55%), which, although small in absolute numbers, corresponds to the global trend of stroke affecting younger populations. The analysis by Ma et al. on the global burden of stroke in adolescents and young adults (1539 years) shows that the incidence in this age group is increasing, which is due to the increased prevalence of risk factors such as overweight, smoking, hypertension and a sedentary lifestyle. [5].

Sex Distribution: The higher representation of women (57.7%) compared to men (42.4%) in our study is consistent with global data showing that women have longer life expectancy and reach older age categories where risk is highest [3]. The global analysis by Qian et al. shows that stroke incidence in women is increasing faster compared to men, partly due to the higher prevalence of atrial fibrillation and hypertension in advanced age among the female population [3]. Additionally, metabolic risk factors, according to WSO, account for 69% of the total stroke burden globally [4], and women more often have uncontrolled hypertension and diabetes in older age.

Acute versus Recurrent Strokes Global Perspectives

Most striking findings in this study is the high proportion of recurrent strokes (re-ictus) of 38.5%. Global data on recurrent stroke rates vary, but meta-analyses show that the cumulative risk for recurrent stroke is 3-10% in the first year and up to 25% in the first five years after the initial incident [6]. The rate of 38.5% in study is significantly higher than the global average, ndicating suboptimal secondary prevention. This is particularly concerning because, according to the AHA/ASA 2026 guidelines, early initiation of secondary prevention can reduce the risk of recurrent incident by 20-30% [7][8]. Encouragingly, the trend of increasing acute cases and parallel decline in recurrent cases, particularly pronounced in 2025 (70.9% acute, 29.1% recurrent), corresponds with global efforts to improve primary and secondary prevention. The study by Wiyarta et al. on prehospital care in low- and middle- income countries emphasizes that educational campaigns and improved infrastructure can significantly reduce delays and improve outcomes [9].

Transport and Prehospital Care Comparison with Global Standards

Analysis of patient transport to hospital reveals significant improvement over the five-year period, with an increase from 57.0% in 2021 to 72.6% in 2025. This trend is consistent with global recommendations for strengthening prehospital systems. The updated AHA/ASA 2026 guidelines [7][8] and the consensus document of the EAN and SO [10] emphasize the crucial role of prehospital services in the identification, triage, and rapid transport of stroke patients.

Comparative Analysis of Transport Rates: According to the RES-Q (Registry of Stroke Care Quality) analysis which included 334,184 patients from 1,130 hospitals in 70 countries, the rate of transport via Emergency Medical Services varies significantly across regions: 87% in Europe, 39% in Latin America, 34% in Africa, and 30% in Asia [11]. Our rate of 72.6% in 2025 approaches the European average, which is an encouraging finding. The same study shows that patients transported via EMS have a median time from symptoms to hospital of 193 minutes, compared to 309 minutes for those arriving by private transport a difference of nearly 2 hours [11]. Additionally, transport via EMS is associated with a three times higher likelihood of receiving intravenous thrombolysis (44% vs. 16%) [11].

Implications for Reperfusion Therapy: The high transport rate in 2025 (72.6%) creates potential space for increasing thrombolysis and mechanical thrombectomy rates in Skopje. However, the study by Kamberi [12] in Tetovo showed that only two thrombolysis procedures were performed during the one-year period, indicating a gap between prehospital transport and in-hospital treatment. This is consistent with global findings that in low- and middle-income countries, reperfusion therapy rates remain low despite improvements in the prehospital phase [9].

Challenges in Prehospital Care A Global Perspective

Despite significant progress, 37.4% non-transported cases in the total period (2,605 patients) represent a challenge. These cases include patients in terminal phase, refusal of transport, cases with mild symptoms, and possible assessment errors. The global review by Wiyarta et al. identifies similar challenges in low- and middle-income countries: lack of public awareness of stroke symptoms, sociodemographic and cultural variables, and insufficient health infrastructure [9]. The study by Vojtikiv Samoilovska et al. [13] in the Southwestern region of North Macedonia confirms that 44% of respondents could not identify any risk factor, and 46% did not know how to recognize symptoms, which directly affects decisions to call EMS and accept transport.

Innovative Solutions: Global literature offers several innovative solutions for reducing prehospital delays, which could be applied in Skopje:

• Mobile Stroke Units: According to the AHA and ASA 2026 guidelines, mobile stroke units allow early identification and treatment of patients who may be eligible for thrombolytic therapy, while clinical studies have demonstrated their safety and clinical benefit [7][8].

• Community Educational Campaigns: Advances in technology, together with targeted public education initiatives, may contribute to improved awareness of stroke symptoms and encourage faster response in emergency situations [9].

• Telemedicine: Although the European Academy of Neurology guidelines [10] indicate limited feasibility studies, telemedicine in ambulances could enable early consultation with a neurologist and better triage.

Comparison with Countries of Similar Socio-Economic Development

According to Global Burden of Disease data, countries in Eastern Europe and Central Asia have the highest stroke incidence rates [3]. North Macedonia, according to statements by the President of the Macedonian Neurological Association, Prof. Dr. Dragana Petrovska-Cvetkovska, is in the "red zone" on the world map both in terms of morbidity and mortality rates [14]. This places our country among the regions with the highest burden of cerebrovascular diseases. Comparison with other countries in the region (Serbia, Croatia, Bulgaria) shows similar trends, but also variations in transport and treatment rates. The RES-Q study [11] shows that European countries have an average transport rate of 87%, higher than our 72.6%, indicating room for further improvement.

Future Perspectives and Projections

According to projections using the Nordpred model, global stroke incidence is expected to increase by 20.3% by 2046, and mortality by 35.7%, primarily in countries with low and medium socio-demographic index [2]. These projections emphasize the urgent need to strengthen preventive strategies and health systems in countries like North Macedonia. The Chinese study on global stroke burden predicts that by 2050, global costs associated with stroke will exceed 1.8 trillion dollars, with the largest increase in developing countries [5]. This highlights the economic dimension of the problem and the need for investment in prevention and treatment.

CONCLUSION

This retrospective study provides a comprehensive and detailed insight into the epidemiological characteristics and prehospital care of stroke patients managed by the Emergency Medical Service in Skopje over a five-year period, from 2021 to 2025.

The findings confirm that stroke represents a significant burden on the emergency medical system, with a total of 6,966 cases registered, averaging 1,393 annually. The demographic analysis reveals that stroke in Skopje is predominantly a disease affecting the elderly, with 88.0% of cases occurring in individuals over the age of 60. Furthermore, the condition is more prevalent among women (57.7%) compared to men (42.4%), a disparity largely attributed to the longer life expectancy and higher accumulation of risk factors in the older female population. A critical finding of the study is the high proportion of recurrent strokes, which stands at 38.5%. This points to suboptimal secondary prevention and underscores an urgent need to strengthen follow-up care and pharmacological management for stroke survivors to prevent future incidents. On a positive note, the data shows an encouraging trend of increasing acute cases and a corresponding decrease in recurrent strokes, most notably in 2025 where acute cases reached 70.9%. Regarding prehospital care, the rate of patient transport to hospital facilities has shown continuous and significant improvement, rising from 57.0% in 2021 to 72.6% in 2025. This 15.6-percentage-point increase suggests progress in field team education, the application of stroke recognition protocols, and enhanced collaboration with hospital stroke units. Despite this improvement, the fact that 37.4% of patients (2,605 individuals) were not transported remains a substantial challenge for the healthcare system. Based on these findings, the study outlines several critical implications for public health and prehospital care. There is a clear need for targeted preventive strategies focused on the most vulnerable groupsspecifically the elderly and women with an emphasis on managing hypertension, lipid disorders, and atrial fibrillation. Strengthening secondary prevention through intensive follow-up for stroke survivors is esential to reduce the risk of recurrence. Finally, improving collaboration between emergency services and hospitals through pre-notification systems and joint protocols, along with establishing continuous monitoring of quality indicators, will be key to enhancing timely care and patient outcomes.

In conclusion, this study establishes essential baseline epidemiological data for prehospital stroke care in Skopje. It provides a solid, evidence-based foundation for developing targeted protocols, implementing preventive strategies, and guiding future research. Continuous monitoring of trends and adaptation of these strategies to local needs will be crucial in the effort to reduce morbidity and mortality from cerebrovascular diseases in the Republic of North Macedonia.

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