EFFORT: Effect of Pioglitazone on Insulin Resistance, Atherosclerosis Progression and Clinical Course of Coronary Heart Disease

• Sponsor: Ukrainian Medical Stomatological Academy (Other)
• Overall Status: Completed
• CT.gov ID: NCT03011775
• Collaborator: (none)
• Enrollment: 43
• Location: 1
• Arms: 2
• Duration (Months): 34
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

Pioglitazone, a medication of thiazolidinedione group, is capable of triggering the peroxisome proliferator-activated receptors (PPAR-γ). Activation of receptor PPAR-γ regulates carbohydrate and lipid metabolism, immune and inflammatory responses in heart tissues.

Our aim will to study the effect of pioglitazone on insulin resistance, the clinical course of atherosclerosis and coronary heart disease (CHD).

The study will include 43 patients with coronary artery disease. Patients will be divided into the study group - 20 patients, in whom pioglitazone will be included in the combined therapy at a dose of 15 mg 1 time per day in the morning, and the control group - 23 patients receiving standard complex drug therapy over 6 months. Patients will be underwent clinical examination, ultrasound of neck vessels, study of carbohydrate and lipid metabolism.

The end primary points of the study will be the onset of death due to myocardial infarction, coronary revascularization procedures (coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)), or hospitalization for acute coronary syndrome (ACS) or unstable angina (UA).

Predefined secondary end points included carotic atherosclerotic leisure (carotic intima-media thickness, diameter of stenosis, presents of atherosclerotic plaque), systemic inflammation level (the level of C reactive protein), lipid metabolism (levels of serum total cholesterol, triglycerides, high and low density lipoproteins), level of insulin resistance ( oral glucose tolerance test, blood glucose).

Condition or Disease	Intervention/Treatment	Phase
Adverse Effect; Atherosclerosis, Coronary; Insulin Resistance Syndrome	Drug: Pioglitazone 15 mg Tablet; Drug: Isosorbide Dinitrate 10Mg Tablet; Drug: Acetylsalicylic Acid 75Mg Tablet; Drug: Bisoprolol Fumarate 2.5 MG Oral Tablet; Drug: Rosuvastatin Calcium 20 MG Oral Tablet; Drug: Ramipril 5 MG	Phase 4

Detailed Description

The study will include 43 people aged between 45 and 68 who suffered from ischemic heart disease. Before starting the study, all participants will give written informed consent, will be obtained of the Commission on Bioethics at Ukrainian Medical Stomatological Academy. Inclusion criteria will be as follows: stable exertional angina, type 2 diabetes mellitus (DM) without receiving injectable antidiabetic drugs. Exclusion criteria will be: the presence of myocardial infarction history, intervention, malignant arterial hypertension (AH), chronic heart failure (HF) of III-IV functional class (FC), systemic connective tissue diseases, cancer and oncohematological diseases, severe infectious diseases, chronic inflammatory diseases, history of acute cerebrovascular accidents, disorders of cardiac rhythm by atrial fibrillation type. The end study will be the primary points: the onset of death due to myocardial infarction, coronary revascularization procedures (coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)), or hospitalization for acute coronary syndrome (ACS) or unstable angina (UA).

The diagnosis of CHD in patients will confirmed by the presence of FC I-III angina according to the classification of the Canadian Cardiovascular Society and the phenomena of circulatory insufficiency according to the classification of New York Heart Association (NYHA). Bicycle ergometry will perform on "Veloergotest 05" (Ukraine) via step increasing loading capacity with a consequent increase under control of electrocardiogram (ECG) and BP. The force of step I will be 150 kgm / min (25 W); II - 300 kgm / min (50 W); III - 450 kgm / min (75 W); IV - 600 kgm / min (100 W); V - 750 kgm / min (125 W); VI - 900 kgm / min (150 W), the duration of each step was 3 minutes. Tolerance of CHD patients to exercise will calculate from the value of the threshold load capacity and volume of work performed. The threshold load capacity of 150 kgm / min (25 W) was considered very low and consistent with angina FC IV; 300 kgm / min (50 W) - low, FC III; 450-600 kgm / min (75-100 W) - average, FC II; 750 kgm / min (125 W) and above - high exercise capacity, FC I. The criteria will cease bicycle ergometry termination conventional clinical or ECG signs of myocardial ischemia.

Prior to inclusion in the clinical trial, all patients will receive conventional treatment and will screening examination to verify the diagnosis of coronary heart disease and type 2 diabetes.

After screening, we will selected 43 patients who received standard medical therapy complex:

isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also will receive recommendations on diet and lifestyle changes. Patients will receive the conventional treatment for at least one month to achieve stable parameters.

On the first day of the study, blood samples will take from all patients, clinical examination was conducted. After clinical and laboratory studies, patients will randomized by gender, age and severity of clinical manifestations of coronary heart disease. As a result of randomization, patients will divide into the study group (n = 20) and control group (n = 23). The complex therapy of the study group will include pioglitazone 15 mg 1 time per day in the morning ("Pioglar", Ranbaxy, India) for 6 months. Patients of the control group will continue to receive only a standard set of drug therapy. Re-examination will carry out in 6 months.

The examination will include the collection of medical history and objective data (gender, age, overweight and obesity, hypertension, type 2 diabetes). Patients will evaluate by anthropometric indicators (height, weight, body mass index (BMI)), blood pressure - systolic and diastolic (SBP and DBP), heart rate (HR) will measure, ECG will register.

In order to determine the status of vascular bed, patients will underwent ultrasonography (US) of neck vessels on "ULTIMA PA", sensor L5 - 12/40, in accordance with standard protocols in B-mode on the three levels of vascular bed and bilaterally at the end of diastole: in the proximal, medial and distal points at a distance of 1 cm from the bifurcation of the posterior wall of the right and left common carotid artery (RCCA and LCCA, respectively) as more distant from the transducer unit. Contour of the carotid arteries will register, their inner lumen, indicators for ASP presence (size, localization) will record, as well as IMT of the carotid arteries. IMT will measure as the distance between the first and the second echogenic lines of located site according to the procedure Pignoli P. et al. The diameter of RCCA, LCCA, and the internal carotid artery (ICA) will assess at the end of systole and diastole as the distance between the IMT. Normal IMT will consider less than 0.9 mm; CCA IMT

1.4 mm was evaluated as ASP, and in the range of 1.0-1.3 mm as the thickening of IMT (ESH, ESC, 2007). The standard criteria for the diagnosis of hemodynamically significant stenosis are the narrowing of the arterial lumen by more than 50%.

The volume of laboratory tests will includ general clinical and biochemical blood analysis. For the control of carbohydrate metabolism glycemic profiles will study determining fasting glucose and after 1 hour after taking 75 g of glucose (oral glucose tolerance test, OGTT) via glucose oxidase method; hyperglycemic factor will calculate. In all patients lipid profile will studied: total cholesterol (TC), triglycerides (TG) and cholesterol of high-density lipoproteins (HDL) ("Diakon-DS", Russia), content of cholesterol in low-density lipoproteins (LDL) and very low density lipoproteins (VLDL) will calculate, as well as atherogenic factor (AF). Study of the inflammatory response will conduct by determining the concentration of basic biomarkers - high-sensitivity C-reactive protein (hs-CRP, "DRG", USA), human tissue inhibitor of metalloproteinase-1 (TIMP-1, "eBioscience", Austria) according to the manufacturer's protocols of test systems via immunoenzyme method. The presence of microalbuminuria will determine using test strips "Mikroalbufan" ("Lachema", Czech Republic), the ratio albumin / creatinine in urine will calculated.

Statistical processing will perform using software "Statistica 6.0" (StatSoft, USA) with calculation of average (M) and standard error of the average (m). Methods of descriptive statistics will use, comparison of performance in groups will perform by parametric (Student's t-test) and non-parametric (Pearson χ2 test, Fisher's exact test, Mann-Whitney test) statistics. For all types of analysis the differences at p <0.05 will consider statistically significant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Effect of Pioglitazone on Insulin Resistance, Progression of Atherosclerosis and Clinical Course of Coronary Heart Disease
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pioglitazone + Standard Care 20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.	Drug: Pioglitazone 15 mg Tablet; Pioglar (Ranbaxy India):1 tablet per day in the morning for 6 months; Other Names: Oral hypoglycemic agent ; Drug: Isosorbide Dinitrate 10Mg Tablet; 1-2 tablets 2 times a day; Other Names: Antianginal, vasodilator agent ; Drug: Acetylsalicylic Acid 75Mg Tablet; 1 tablet per a day; Other Names: NSAID and antiplatelet agent ; Drug: Bisoprolol Fumarate 2.5 MG Oral Tablet; 1 tablet per a day; Other Names: Lowering high blood pressure agent ; Drug: Rosuvastatin Calcium 20 MG Oral Tablet; 1 tablet per a day; Other Names: Lipid- lowering agent ; Drug: Ramipril 5 MG; 1 tablet per a day; Other Names: ACE inhibitor
Other: Standard Care 23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.	Drug: Isosorbide Dinitrate 10Mg Tablet; 1-2 tablets 2 times a day; Other Names: Antianginal, vasodilator agent ; Drug: Acetylsalicylic Acid 75Mg Tablet; 1 tablet per a day; Other Names: NSAID and antiplatelet agent ; Drug: Bisoprolol Fumarate 2.5 MG Oral Tablet; 1 tablet per a day; Other Names: Lowering high blood pressure agent ; Drug: Rosuvastatin Calcium 20 MG Oral Tablet; 1 tablet per a day; Other Names: Lipid- lowering agent ; Drug: Ramipril 5 MG; 1 tablet per a day; Other Names: ACE inhibitor

Outcome Measures

Primary Outcome Measures

1. Сardiovascular Death [Baseline and 1 year]

   Number of Participants with cardiovascular death

2. Coronary Artery Bypass [Coronary Revascularization] [Baseline and 1 year]

   Number of Participants with revascularization coronary procedures (coronary artery bypass grafting)

3. Cardiovascular Hospitalization [Baseline and 1 year]

   Number of Participants with acute coronary syndrome (ACS) or unstable angina (UA)

4. Percutaneous Coronary Intervention [Coronary Revascularization] [Baseline and 1 year]

   Number of Participants with incidence of percutaneous coronary intervention.

5. Safety and Tolerability 1 [Baseline, 6 month and 1 year]

   Liver injury: mean values of ALT

6. Safety and Tolerability 2 [Baseline, 6 month and 1 year]

   Liver injury: mean levels of total bilirubin

7. Safety and Tolerability 3 [Baseline and 1 year]

   Kidney injury: mean values of the microalbuminuria

8. Safety and Tolerability 4 [Baseline and 1 year]

   Kidneys injury: mean values of creatinine

Secondary Outcome Measures

1. Thickness of the Intima-media Complex [Baseline, 6 month and 1 year]

   Mean thickness of carotid intima-media complex

2. Diameter of Stenosis [Carotic Atherosclerotic Lesions] [Baseline and 1 year]

   Mean diameters of the stenosis of the right and left common carotid arteries

3. Carotic Atherosclerotic Lesions [Baseline and 1 year]

   Number of Participants with presence of atherosclerotic plaque of the intima media of common carotid artery greater than 1.4 mm

4. Systemic Inflammation Level [Baseline and 1 year]

   Number of Participants with C-reactive protein level above 3 mg/L

5. Lipid Metabolism 1 [Baseline, 6 month and 1 year]

   Mean levels of total serum cholesterol

6. Lipid Metabolism 2 [Baseline, 6 month and 1 year]

   Mean values of the triglyceride levels

7. Lipid Metabolism 3 [Baseline and 1 year]

   Lipoproteine fractions:mean values of high-density lipoproteins and low density lipoproteins

Other Outcome Measures

1. Level of Insulin Resistance 1 [6 months]

   Oral glucose tolerance test: number of Participants with impaired glucose tolerance

2. Level of Insulin Resistance 2 [Baseline and 6 months]

   Mean levels of blood glucose

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 68 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• stable exertional angina,

• type 2 diabetes mellitus (DM) without receiving injectable antidiabetic drugs

Exclusion Criteria:

• the presence of myocardial infarction history, intervention;

• malignant arterial hypertension (AH);

• chronic heart failure (HF) of III-IV functional class (FC);

• systemic connective tissue diseases;

• cancer and oncohematological diseases, severe infectious diseases, chronic inflammatory diseases;

• history of acute cerebrovascular accidents;

• disorders of cardiac rhythm by atrial fibrillation type.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ukrainian Medical Stomatological Academy	Poltava		Ukraine	36011

Sponsors and Collaborators

• Ukrainian Medical Stomatological Academy

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Struijker Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Kjeldsen SE, Erdine S, Narkiewicz K, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Cifkova R, Dominiczak A, Fagard R, Heagerty AM, Laurent S, Lindholm LH, Mancia G, Manolis A, Nilsson PM, Redon J, Schmieder RE, Struijker-Boudier HA, Viigimaa M, Filippatos G, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Kiowski W, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Viigimaa M, Waeber B, Williams B, Zamorano JL, The task force for the management of arterial hypertension of the European Society of Hypertension, The task force for the management of arterial hypertension of the European Society of Cardiology. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007 Jun;28(12):1462-536. Epub 2007 Jun 11.

• Responsible Party: Igor Kaydashev, Head of Internal Medicine Department #3, Ukrainian Medical Stomatological Academy
• ClinicalTrials.gov Identifier: NCT03011775
• Other Study ID Numbers: CT-18-06-2012
• First Posted: Jan 5, 2017
• Last Update Posted: Mar 10, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Igor Kaydashev, Head of Internal Medicine Department #3, Ukrainian Medical Stomatological Academy: Pioglitazone, Insulin Resistance; Atherosclerosis, Coronary Heart Disease
• Additional relevant MeSH terms: Heart Diseases; Atherosclerosis; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Insulin Resistance; Metabolic Syndrome; Aspirin; Pioglitazone; Hypoglycemic Agents; Ramipril; Bisoprolol; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate; Vasodilator Agents; Platelet Aggregation Inhibitors; Rosuvastatin Calcium

Study Results

Participant Flow

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Period Title: Overall Study
STARTED	20	23
COMPLETED	20	23
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Pioglitazone + Standard Care	Standard Care	Total
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	Total of all reporting groups
Overall Participants	20	23	43
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 95%	22 95.7%	41 95.3%
>=65 years	1 5%	1 4.3%	2 4.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (1.15)	53 (1.36)	53.7 (5.9)
Sex: Female, Male (Count of Participants)
Female	8 40%	7 30.4%	15 34.9%
Male	12 60%	16 69.6%	28 65.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	20 100%	23 100%	43 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Ukraine	20 100%	23 100%	43 100%

Outcome Measures

1. Primary Outcome

Title	Сardiovascular Death
Description	Number of Participants with cardiovascular death
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Baseline	0 0%	0 0%
1 year	0 0%	0 0%

2. Primary Outcome

Title	Coronary Artery Bypass [Coronary Revascularization]
Description	Number of Participants with revascularization coronary procedures (coronary artery bypass grafting)
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Baseline	0 0%	0 0%
1 year	0 0%	0 0%

3. Primary Outcome

Title	Cardiovascular Hospitalization
Description	Number of Participants with acute coronary syndrome (ACS) or unstable angina (UA)
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Baseline	0 0%	0 0%
1 year	0 0%	0 0%

4. Primary Outcome

Title	Percutaneous Coronary Intervention [Coronary Revascularization]
Description	Number of Participants with incidence of percutaneous coronary intervention.
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day During the observation of mortality from all-cause mortality, serious adverse events, other (Not Including Serious) adverse events among patients of study groups not recorded.	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day During the observation of mortality from all-cause mortality, serious adverse events, other (Not Including Serious) adverse events among patients of control groups not recorded.
Measure Participants	20	23
Baseline	0 0%	0 0%
1 year	0 0%	0 0%

5. Primary Outcome

Title	Safety and Tolerability 1
Description	Liver injury: mean values of ALT
Time Frame	Baseline, 6 month and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Baseline	23.4 (2.4)	26.9 (2.57)
Mean values of ALT in 6 months	27.4 (2.1)	26.1 (1.68)
Mean values of ALT in 1 year	19.9 (1.9)	23.9 (1.19)

6. Primary Outcome

Title	Safety and Tolerability 2
Description	Liver injury: mean levels of total bilirubin
Time Frame	Baseline, 6 month and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: Pioglar (Ranbaxy India):1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day Ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day Ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Baseline	12.3 (1.3)	10.8 (1.01)
Mean values of total bilirubin in 6 month	12.4 (1.02)	12.7 (1.05)
Mean values of total bilirubin in 1 year	15.7 (1.6)	15.0 (5.9)

7. Primary Outcome

Title	Safety and Tolerability 3
Description	Kidney injury: mean values of the microalbuminuria
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day During the observation of mortality from all-cause mortality, serious adverse events, other (Not Including Serious) adverse events among patients of study groups not recorded.	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day During the observation of mortality from all-cause mortality, serious adverse events, other (Not Including Serious) adverse events among patients of control groups not recorded.
Measure Participants	20	23
Baseline	31.44 (4.28)	41.1 (4.85)
1 year	31.10 (5.00)	37.70 (4.48)

8. Primary Outcome

Title	Safety and Tolerability 4
Description	Kidneys injury: mean values of creatinine
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Mean values of creatinine in men baseline	105.6 (38.5)	102.3 (43.1)
Mean values of creatinine in men in 1 year	85.0 (21.1)	82.0 (14.0)
Mean values of creatinine in women baseline	66.8 (8.8)	88.2 (11.1)
Mean values of creatinine in women in 1 year	72.5 (8.1)	77.5 (18.0)

9. Secondary Outcome

Title	Thickness of the Intima-media Complex
Description	Mean thickness of carotid intima-media complex
Time Frame	Baseline, 6 month and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Mean thickness of the right carotid intima-media baseline	1.08 (0.17)	0.98 (0.15)
Mean thickness of the right carotid intima-media in 6 month	1.05 (0.13)	0.97 (0.11)
Mean thickness of the right carotid intima-media in 1 year	1.01 (0.02)	1.01 (0.01)
Mean thickness of the left carotid intima-media baseline	1.1 (0.18)	1.0 (0.15)
Mean thickness of the left carotid intima-media in 6 month	1.06 (0.13)	1.00 (0.10)
Mean thickness of the left carotid intima-media in 1 year	1.02 (0.02)	0.97 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pioglitazone + Standard Care, Standard Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	The threshold for statistical significance was P value of .05

10. Secondary Outcome

Title	Diameter of Stenosis [Carotic Atherosclerotic Lesions]
Description	Mean diameters of the stenosis of the right and left common carotid arteries
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Mean diameter of the stenosis of the right common carotid artery baseline	9.8 (3.1)	8.7 (2.7)
Mean diameter of the stenosis of the right common carotid artery in 1 year	5.0 (1.8)	4.8 (1.5)
Mean diameter of the stenosis of the left common carotid artery baseline	11.6 (3.6)	10.1 (3.0)
Mean diameter of the stenosis of the left common carotid artery in 1 year	4.1 (1.7)	5.6 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pioglitazone + Standard Care, Standard Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Chi-squared
	Comments

11. Secondary Outcome

Title	Carotic Atherosclerotic Lesions
Description	Number of Participants with presence of atherosclerotic plaque of the intima media of common carotid artery greater than 1.4 mm
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Baseline	0 0%	0 0%
1 year	0 0%	0 0%

12. Secondary Outcome

Title	Systemic Inflammation Level
Description	Number of Participants with C-reactive protein level above 3 mg/L
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Baseline	10 50%	7 30.4%
In 1 year	12 60%	13 56.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pioglitazone + Standard Care, Standard Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Chi-squared
	Comments

13. Secondary Outcome

Title	Lipid Metabolism 1
Description	Mean levels of total serum cholesterol
Time Frame	Baseline, 6 month and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Mean values of the total cholesterol level baseline	5.27 (0.2)	5.28 (1.0)
Mean values of the total cholesterol level in 6 month	4.5 (0.2)	4.3 (0.2)
Mean values of the total cholesterol level in 1 year	4.5 (0.2)	4.3 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pioglitazone + Standard Care, Standard Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

Title	Lipid Metabolism 2
Description	Mean values of the triglyceride levels
Time Frame	Baseline, 6 month and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Mean values of triglyceride baseline	0.69 (0.1)	0.61 (0.21)
Mean values of triglyceride in 6 month	0.72 (0.40)	0.73 (0.25)
Mean values of triglyceride in 1 year	0.9 (0.1)	0.7 (0.1)

15. Secondary Outcome

Title	Lipid Metabolism 3
Description	Lipoproteine fractions:mean values of high-density lipoproteins and low density lipoproteins
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Mean values of high-density lipoproteins in men baseline	0.8 (0.2)	0.9 (0.4)
Mean values of high-density lipoproteins in men in 1 year	1.1 (0.3)	1.0 (0.3)
Mean values of high-density lipoproteins in women baseline	0.9 (0.3)	1.1 (0.2)
Mean values of high-density lipoproteins in women in 1 year	1.2 (0.2)	1.0 (0.2)
Mean values of low density lipoproteins in men baseline	3.9 (0.7)	4.4 (0.8)
Mean values of low density lipoproteins in men in 1 year	2.9 (0.5)	3.0 (0.6)
Mean values of low density lipoproteins in women baseline	4.5 (0.8)	3.5 (0.8)
Mean values of low density lipoproteins in women in 1 year	3.3 (0.8)	2.7 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pioglitazone + Standard Care, Standard Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

16. Other Pre-specified Outcome

Title	Level of Insulin Resistance 1
Description	Oral glucose tolerance test: number of Participants with impaired glucose tolerance
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Number of Participants with glucose level in the range of 7.8 to 11 mmol/L baseline	7 35%	14 60.9%
Number of Participants with glucose level in the range of 7.8 to 11 mmol/L in 6 month	13 65%	16 69.6%
Number of Participants with glucose level above 11 mmol/L baseline	10 50%	4 17.4%
Number of Participants with glucose level above 11 mmol/L in 6 month	5 25%	3 13%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pioglitazone + Standard Care, Standard Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Chi-squared
	Comments

17. Other Pre-specified Outcome

Title	Level of Insulin Resistance 2
Description	Mean levels of blood glucose
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone + Standard Care	Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day	23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
Measure Participants	20	23
Baseline	6.0 (0.1)	5.9 (0.54)
In 6 month	5.97 (0.20)	5.60 (0.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pioglitazone + Standard Care, Standard Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.3
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	1 year
Arm/Group Title	Pioglitazone + Standard Care		Standard Care
Arm/Group Description	20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months. Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day		23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day ramipril 5 MG: 1 tablet per a day
All Cause Mortality
	Pioglitazone + Standard Care		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/23 (0%)
Serious Adverse Events
	Pioglitazone + Standard Care		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Pioglitazone + Standard Care		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.