Clinical and Pharmacoeconomic Effectiveness of Thrombolytic Therapy for ST-Segment Elevation Myocardial Infarction in Real Clinical Practice

The dissertation is devoted to the assessment of the clinical and pharmacoeconomic effectiveness of thrombolytic therapy (TLT) in patients with ST-segment elevation myocardial infarction (STEMI) under conditions of real clinical practice. The study addresses the safety and efficacy of thrombolytic agents administered at the pre-hospital and in-hospital stages of care, including the feasibility of TLT administration by linear emergency medical service teams with telemetric support. The research also analyzes clinical outcomes, complication rates, and mortality within 12 months after hospitalization, along with direct costs and cost-effectiveness indicators for different thrombolytic agents, including the domestic drug "Purolase" (recombinant prourokinase).

RELEVANCE OF THE PROBLEM

Reperfusion therapy is the most important component of the treatment strategy for ST-segment elevation myocardial infarction (STEMI). Thrombolytic therapy (TLT), which in recent years, especially in the West, has yielded its leading position as the main reperfusion method to percutaneous coronary interventions (PCI), remains the most accessible treatment method, mandatory in the absence of contraindications or when PCI is unavailable; the importance of its earliest possible administration, preferably at the pre-hospital stage of care, is emphasized [21, 94, 114, 142, 153, 217].

At the same time, most of the data on the effectiveness of reperfusion with PCI or TLT have been obtained in large randomized controlled trials (RCTs), in which the patient population differs from that existing in the "real world" or "real practice." Higher mortality has been described among "unselected" MI patients than in RCTs and registries [158, 210], which makes it necessary to conduct studies evaluating the safety and effectiveness of any intervention under conditions of actual clinical practice [105, 119].

The implementation of clinical guidelines into practice remains a problem in all countries [207]. The gap between science and practical medicine is reflected in the failure to perform reperfusion in approximately 23–33% of patients in whom it is clearly indicated [131, 217].

In our country there is relatively limited experience in maintaining a STEMI registry, according to which TLT (in 97% of cases with streptokinase) was performed in 12.9% of patients and PCI in 1.2% [86]. When the results of the HERO-2 study were discussed at a meeting of the American Heart Association in 2001, in which all study participants were required to receive TLT, it turned out that in Russian centers only 14% of patients not enrolled in the study received TLT, compared with 96% of patients in the USA [7].

According to later data, TLT for ST-segment elevation myocardial infarction is performed in less than 20% of cases, including in megacities in 13%, in medium-sized cities in 19%, and in rural areas in 9% [13].

It is believed that in the treatment of MI, not so much the choice of the thrombolytic agent (TLA) matters as the earliest possible administration of thrombolysis [35, 157]; TLT can and should be performed not only by cardiologists but also by general practitioners and paramedics [94, 142, 175].

The use of TLA by emergency medical service (EMS) teams in the Russian Federation is hindered primarily by organizational and financial difficulties [11], and TLT for STEMI is performed by specialized cardiology teams, while experience with pre-hospital TLT has been accumulated mainly either within RCTs or within specially organized studies [26, 34, 72, 83].

In the Russian Federation, relatively few pharmacoeconomic studies of TLT have been conducted; they have demonstrated the benefit of in-hospital TLT compared with management without thrombolysis and have carried out a comparative pharmacoeconomic analysis of streptokinase and alteplase [5, 15].

However, the actual cost of treating a cardiology patient has not been determined [5, 15], and the authors have not encountered an analysis of the pharmacoeconomic effectiveness of pre-hospital TLT in the Russian literature.

Thus, the assessment of the safety and effectiveness of pre-hospital TLT for STEMI in actual practice, including when performed by linear EMS teams, as well as the pharmacoeconomic analysis of pre-hospital TLT, are relevant problems.

AIM OF THE STUDY - to assess the safety and clinical effectiveness of TLT at the in-hospital and pre-hospital stages in actual clinical (treatment) practice, to conduct a comparative pharmacoeconomic analysis of in-hospital and pre-hospital TLT, and to develop recommendations for optimizing the care of MI patients with ST-segment elevation.

OBJECTIVES OF THE STUDY

1. To analyze the safety of TLT performed by cardiology and linear ambulance teams, assessed by the frequency of TLT and MI complications at the pre-hospital and in-hospital stages of care for MI patients.

2. To conduct a comparative analysis of in-hospital and pre-hospital TLT in actual clinical practice according to indicators reflecting:

- time delays in the onset of reperfusion;

- the adequacy of assessment of indications/contraindications for TLT by ambulance physicians and specialized hospital physicians;

- the clinical course of MI during hospitalization; the frequency of cardiovascular events (hospitalizations for cardiovascular diseases, death from cardiovascular diseases) within 12 months after hospitalization.

3. To analyze the direct costs (cost of main therapy and treatment of complications) of treating ST-segment elevation MI in the DTLT group and in the GTLT group.

4. To conduct a cost-effectiveness analysis in the pre-hospital and in-hospital TLT groups.

5. To analyze the safety and effectiveness of pre-hospital and in-hospital TLT with recombinant prourokinase (Purolase) according to the frequency of TLT and MI complications and the frequency of cardiovascular events during hospitalization and within 12 months after hospitalization.

6. To conduct a comparative pharmacoeconomic analysis of TLT at the in-hospital and pre-hospital stages of care for MI patients for recombinant prourokinase, tenecteplase, and alteplase.

STATEMENTS DEFENDED

1. EMS cardiology teams possess sufficient qualifications for the diagnosis (diagnostic accuracy 95%) of acute myocardial infarction and the administration of TLT. Linear EMS teams can administer TLT if telemetric support is organized, allowing round-the-clock ECG transmission to a specialized center and real-time consultation with an emergency cardiology specialist.

2. The administration of TLT by linear EMS teams under conditions of actual clinical practice is comparable in clinical effectiveness and safety to TLT administered by cardiology teams and is superior in clinical effectiveness to TLT administered in a specialized hospital, as manifested by reduced mortality, shorter hospital stay, and lower complication rates; the effect persists for at least 12 subsequent months. TLT administered by linear teams is not accompanied by an increase in the frequency of pre-hospital TLT and MI complications.

3. The transfer of TLT to the pre-hospital stage of care for MI patients with ST-segment elevation is economically advantageous compared with TLT administered in hospital, since it allows reducing treatment costs both during hospitalization and within 12 months after the myocardial infarction.

4. Pre-hospital TLT with recombinant prourokinase (Purolase) is safe and effective from both clinical and economic perspectives.

PRACTICAL SIGNIFICANCE

It has been shown that the actual practice of care for STEMI patients established in the city of Saratov, which provides for calling linear EMS teams upon suspected MI "to themselves" by EMS cardiology teams, leads to a significant delay in the initiation of reperfusion therapy, which is associated with increased in-hospital and 12-month mortality, as well as longer hospital stay due to a higher frequency of MI complications.

From an economic standpoint, it is advisable to administer TLT at the pre-hospital stage of care, which will reduce both hospitalization costs and costs during at least 12 months after the MI.

Based on the results obtained, it is possible to recommend the implementation of TLT at the pre-hospital stage of care for STEMI patients not only by specialized cardiology teams but also by linear EMS teams, which requires establishing a system of telemetric support for linear teams (and, prospectively, all first-contact physicians).

The domestic third-generation thrombolytic agent "Purolase" (recombinant prourokinase) can be recommended for pre-hospital TLT due to its clinical and pharmacoeconomic effectiveness.

The results of the work have been implemented in the practice of care for STEMI patients at the Saratov Research Institute of Cardiology, City Clinical Hospital No. 2 of the city of Saratov, and the Municipal Medical Institution "Emergency Medical Service of the City of Saratov," and are used for training clinical residents in the specialty "cardiology" at the Saratov Research Institute of Cardiology.

SCIENTIFIC NOVELTY

For the first time, an analysis of TLT for STEMI under conditions of actual clinical practice by ambulance teams has been performed, and it has been shown that the organizational features of care for STEMI patients, which provide for calling linear EMS teams upon suspected MI "to themselves" by EMS cardiology teams, lead to a substantial increase in "symptom-to-needle" time, i.e., a considerably later onset of reperfusion.

For the first time in the Russian Federation, the safety and clinical effectiveness of TLT administered by linear EMS teams have been demonstrated.

For the first time, a pharmacoeconomic analysis of pre-hospital and in-hospital TLT has been performed, and a reduction in direct costs and optimization of the cost-effectiveness indicator during hospitalization and within 12 months after the MI have been demonstrated when TLT is transferred to the pre-hospital stage of care.

For the first time, an analysis of the safety, clinical, and pharmacoeconomic effectiveness of TLT for STEMI with the domestic thrombolytic agent "Purolase" (recombinant prourokinase) at the pre-hospital and in-hospital stages has been performed.