Assessment of the Effects of Atorvastatin Therapy on Myocardial Deformation Characteristics, in Patients With STEMI
Condition: Myocardial Infarction
MeSH terms: Myocardial Infarction; Infarction
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary goal

      • To assess the effect of atorvastatin in patients treated since the first 24-96 hours of the
      disease on the parameters of global and regional myocardial deformation in the infarcted area
      and the structural and functional properties of arteries at day 7, at 12, 24, 36 and 48 weeks
      of treatment;

      The secondary goals. To evaluate the effect of treatment:

        -  on the parameters of the global and regional myocardial deformation in the intact area
           on day 7, on 12, 24, 36 and 48 weeks of treatment;

        -  on the parameters of the global and regional myocardial deformation depending on the
           degree of coronary blood flow restoration by thrombolysis in myocardial infarction
           (TIMI)

        -  on systolic and diastolic left ventricular function in the presence of initial
           impairments, or absence of the negative dynamics of these parameters in case of normal
           baseline values;

        -  on the clinical diagnostic criteria for the development or progression of heart failure;

        -  the dynamics of the duration and extent of myocardial ischemia according to the daily
           ECG monitoring on day 7, at 12, 24, 36 and 48 weeks of treatment;

        -  the appearance of new prognostically significant cardiac arrhythmias

        -  on the pulse wave velocity

        -  the thickness of the intima-media complex (IMT); 200 patients are planned to be include
           in a randomized, single-center, open, prospective, controlled clinical trial, the
           enrollment will be held at the Department of "Therapy" of Medical Institute of Penza
           State University.

      Definition of the study group:

      The patients with STEMI (myocardial infarction with ST-segment elevation) will be included in
      the study

        -  Group 1 STEMI - 100 patients receiving atorvastatin 80 mg / day for 48 weeks;

        -  Group 2 STEMI - 100 patients receiving atorvastatin 20 mg / day for 48 weeks Planned
           number of patients: Pre-Screening - 300 subjects; screening and randomization - 200
           subjects.

      Patients will be randomized by random number generation to include in the group 1 or 2. All
      included patients will be on the standard basis therapy of the coronary artery disease,
      according to the national recommendation.
    

Detailed description: 
      1. Hypotheses:

        1. Atorvastatin therapy directly results in improved deformation characteristics of
           hibernating myocardium due to its pleiotropic effects on endothelial dysfunction and
           atherosclerotic plaque stability, as well as stimulation of angiogenesis in ischemic
           zones of myocardium.

        2. Long-term atorvastatin therapy improves the morphofunctional properties of large
           arteries and decreases the severity of endothelial dysfunction in patients with a
           history of myocardial infarction.

        3. Atorvastatin causes an anti-ischemic effect, if used for a long time. 2.1. Primary
           objective To evaluate the effect of atorvastatin, when started between 24 and 96 hours
           after disease onset, on the parameters of global and regional myocardial deformation in
           the zone of infarction, as well as morphofunctional properties of arteries, on Day 7 and
           Weeks 12, 24, 36 and 48 of the treatment; 2.2. Secondary objectives. To evaluate:

             -  the effect of treatment on the parameters of global and regional myocardial
                deformation in the zone of intact myocardium on Day 7 and Weeks 12, 24, 36 and 48
                of the treatment;

             -  the effect of treatment on the parameters of global and regional myocardial
                deformation depending on TIMI blood flow grade;

             -  the effect of treatment on systolic and diastolic function of the left ventricle in
                patients with impaired left ventricular function at baseline, as well as the
                ability of this treatment to prevent deterioration of left ventricular function in
                patients with normal left ventricular function at baseline;

             -  the effect of treatment on heart failure development and progression as assessed
                using the corresponding clinical diagnostic criteria;

             -  the effect of treatment on duration and time course of myocardial ischemia using 24
                hour ECG monitoring on Day 7 and Weeks 12, 24, 36 and 48 of treatment;

             -  the effect of treatment on the appearance of new prognostically significant
                disorders of cardiac rhythm;

             -  the effect of treatment on pulse wave velocity and cardio-ankle vascular index
                (CAVI);

             -  the effect of treatment on intima-media thickness (IMT);

             -  the effect of treatment on the results of automated quantitative vascular
                elasticity measurements, pulse wave and pulse pressure;

             -  the effect of treatment on endothelial function using the reactive hyperemia test;

             -  the effect of treatment on the time course of blood chemistry parameters (i.e.,
                total cholesterol, HDL, LDL, triglycerides, creatinine, C-reactive protein (CRP),
                alanine transaminase (ALT), aspartate transaminase (AST) and creatinkinase (CK);

             -  the safety of treatment;

             -  the effect of treatment on patient's well-being and quality of life;

             -  patient compliance with the therapy. 2.3. Scientific novelty of the study It is
                planned to study, for the first time, the effect of long-term aggressive statin
                therapy on the functional status of myocardium in the zone of ischemia, lesion and
                necrosis in patients with STEMI using the two-dimensional strain procedure.

      It is planned, for the first time, to comprehensively study the effect of aggressive statin
      therapy on the status of vasculature, with measuring multiple parameters characterizing the
      morphofunctional status of elastic and muscular arteries in patients with documented coronary
      heart disease (CHD).

      2.4. Clinical significance of study results. If the proposed hypotheses are confirmed after
      the primary endpoints described in Section 3 have been reached, new convincing evidence
      supporting the use of long-term aggressive treatment with Atorvastatin starting from the
      early stages of myocardial infarction will be obtained. Obviously, the clinical benefits will
      include the improved prognosis and decreased risk of repeated vascular events. Favorable
      effects of this therapy on the morphofunctional status of arterial vasculature will play an
      important role in the treatment of these patients. Positive results of this study can form
      the basis for planning and conducting larger studies on pleiotropic effects of Atorvastatin
      in patients with a history of myocardial infarction.

      3. Primary endpoints

        1. Statistically significant differences in spatial and velocity parameters of myocardial
           deformation in the zone of previous STEMI as compared to controls.

        2. Statistically significant differences in spatial and velocity parameters of myocardial
           deformation in the intact zone after STEMI as compared to controls.

        3. Statistically significant differences in intima-media thickness (IMT) according to echo
           tracking data as compared to controls.

        4. Statistically significant differences in carotid-femoral pulse wave velocity and CAVI as
           compared to controls.

      4. Planning and conducting the study. It is planned to include 200 patients in this
      randomized, open-label, single-center, prospective, controlled clinical study; these patients
      will be recruited at the Department of Therapy of the Penza State University Medical
      Institute.

      4.1. Allocation to study groups:

      Patients with STEMI will be included in this study:

      Group 1: 100 patients with STEMI to receive atorvastatin at a dose of 80 mg per day for 48
      weeks; Group 2: 100 patients with STEMI to receive atorvastatin at a dose of 20 mg per day
      for 48 weeks.

      4.2. Planned number of patients: Prescreening - 300 patients; screening and randomization -
      200 patients.

      4.3. Study design. Patients will be randomized using sealed envelopes numbered with
      increasing serial numbers from 1 to 200; each envelope will contain information about patient
      inclusion into Group 1 or Group 2. Information about treatment schedule and dosing regimen
      will be provided separately.

      4.3.1. Treatment regimen, dose titration strategy and combination treatment principles
      Patients meeting the inclusion criteria and not meeting the exclusion criteria will be
      included in the study.

      Group A patients will start the treatment between 24 and 96 hours after the onset of STEMI:

      • Atorvastatin at a dose of 80 mg per day.

      Group K patients will start the treatment between 24 and 96 hours after the onset of STEMI:

      • Atorvastatin at a dose of 20 mg per day.
    

Intervention name(s): Atorvastatin
Intervention type(s): Drug
Intervention description(s): Lipid-lowering therapy
Other intervention name(s): Statin
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: STEMI; myocardial strain; atorvastatin