DescripTion of the Effectiveness, Safety, Tolerability and Adherence to Amlodipine/atoRvastatin/Perindopril sinGle Pill Combination trEatmenT in Patients With Arterial Hypertension and Dyslipidemia in the Daily Clinical Practice. (TARGET)
Conditions: Arterial Hypertension, HTN
Sponsor: Servier Russia

1 
 
 
Multicenter observational program TARGET 
 
Protocol N° IC4-05153-070-RUS 
 
NCT05764317 
 
DescripTion of the effectiveness, safety, tolerability and 
adherence to Amlodipine/atoRvastatin/perindopril sinGle 
pill combination trEatmenT in patients with arterial 
hypertension and dyslipidemia  in the daily clinical practice. 
 
11\08\2022 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Non-interventional study name: DescripTion of the effectiveness, safety, tolerability and 
adherence to Amlodipine/atoRvastatin/perindopril sinGle pill combination trEatmenT in patients 
with arterial hypertension and dyslipidemia  in the daily clinical practice. (TARGET) 
 
 Protocol №: IC4-05153-070-RUS 
 
INN:  amlodipine+atorvastatin+perindopril  
 
Dosage:  
Amlodipine 5 mg + atorvastatin 10 mg + perindopril arginine  5 mg 
Amlodipine 5 mg + atorvastatin 20 mg + perindopril arginine 5 mg 
Amlodipine 5 mg + atorvastatin 20 mg + perindopril arginine 10 mg 
 
Pharmaceutical form: film-coated tablet  
 
National coordinator:  acad. Irina E. Chazova.  
 
Confidential 
This document is classified by Servier as confidential and is intended only for instructions during 
the observational period. 
The contents of this document should not be disclosed to any persons or institutions not 
participating in this study without the prior written consent of Servier. 
 
Abbreviations 
ACE 
Angiotensin-converting enzyme 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ARB 
Angiotensin receptor blocker 
BL 
Baseline 
BP 
Blood pressure 
CABG 
Coronary artery bypass surgery 

3 
 
CHD 
Coronary heart  disease 
CKD 
Chronic kidney disease 
CHF 
Chronic heart failure 
CRF 
Case report form 
CV 
Cardiovascular 
DAH 
Dyslipidemic arterial hypertension 
DBP 
Diastolic blood pressure 
HTN 
Arterial hypertension 
LDL 
Low-density lipids cholesterol 
SADR 
Serious adverse drug reaction 
SBP 
    Systolic blood pressure 
SPC 
Single pill combination  
 
 
 
 
 
 
 
 
 
 

Contents  
 
1 
Introduction and objectives ..................................................................................................... 4 
1.1 Introduction .......................................................................................................................... 4 
1.2 Objectives ............................................................................................................................ 5 
1.3 Variables .............................................................................................................................. 5 
2 
Methods and documentation .................................................................................................... 7 
2.1 Study design and  rationale for its’ choice ........................................................................... 7 
2.2 Calculation of the sample size ............................................................................................. 8 
2.3 Selection of doctors ........................................................................................................... 12 
2.4 Selection of patients ........................................................................................................... 11 
2.4.1 
Inclusion criteria .................................................................................................... 11 
2.4.2 
Non-inclusion criteria ............................................................................................ 11 
2.5 Treatment during the study ................................................................................................ 12 
2.5.1 Treatment with the studied drug ....................................................................................... 12 
2.5.2 
Concomitant drugs ................................................................................................. 12 
2.6 Duration of non-interventional study ................................................................................. 12 
2.7 Documentation during the non-intervention study ............................................................ 13 
2.7.1. Documentation folder ...................................................................................................... 13 
    2.7.2  Study schedule ............................................................................................................. 13 
2.7.3. Methods and measurements............................................................................................. 13 
2.7.4 Data collection  ................................................................................................................. 14 
    2.7.5  Implementation of non-intervention study .................................................................. 15 
3 
Pharmacovigilance ................................................................................................................ 16 
3.1 Definitions ......................................................................................................................... 16 
3.1.1 
Pharmacovigilance information ............................................................................. 16 
3.1.2 
Adverse Event (AE) ............................................................................................... 16 
3.1.3 
Adverse (drug) reaction (ADR) ............................................................................. 16 
3.1.4 
Serious adverse (drug) reaction (SADR) ............................................................... 16 
3.2 Responsibilities .................................................................................................................. 17 
3.2.1 
Events to be reported ............................................................................................. 17 
3.2.2 
Responsibilities of the investigator ........................................................................ 17 
3.2.3 
Responsibilities of the Sponsor/Marketing Authorisation Holder ......................... 18 
4 
Data management, quality management, statistics and reporting ......................................... 18 
4.1 Data management .............................................................................................................. 18 

5 
 
4.2 Statistical analysis .............................................................................................................. 18 
4.3 Report preparation ............................................................................................................. 19 
5 
Ethical considerations ............................................................................................................ 19 
6 
Appendices ............................................................................................................................ 20 
7 
References ............................................................................................................................. 33 
 
1.1 Introduction  
 
Arterial hypertension  (HTN) is one of the most important risk factors for the progression of 
cardiovascular diseases and plays a crucial role in the clinical course of coronary heart artery 
disease (CHD), peripheral artery disease, stroke, chronic heart failure (CHF) and chronic kidney 
disease (CKD). According to the results of Framingham Heart Study,  more than 80% of  patients 
with  HTN  have additional risk factors. Lipid metabolism disorders play a key role in the 
development of atherosclerosis and are the most important predictors of cardiovascular 
complications in patients with HTN [1]. Dyslipidemia accompanied by HTN is characterized by 
an early development of oxidative stress, endothelial dysfunction and  leads to atherosclerosis 
progression [2-8]. The prevalence of co-existing dyslipidemia and HTN is  from 15 to 31% [9, 
10]. According to  M.L. Johnson et al.  30, 47 and 18% of the population have dyslipidemia and 
HTN , isolated HTN and isolated hypercholerestolemia respectively [11]. According to the results  
of EUROASPIRE III  study that included more than  9 000 of participants with CHD from 22 
countries  including Russia, hypercholesterolemia (total cholesterol ≥4.5 mmol/l) was identified 
in 51% of all cases  [12].  In Framingham Heart Study about 40% of patients with HTN had 
hypercholesterolemia. Co-existing  significant increase  of systolic BP and low density lipoprotein 
cholesterol (LDL-C) levels was associated with an increased risk of major CV events  in  a 10 year 
perspective [1].   It has been clearly demonstrated that for patients with  a combination of 
dyslipidemia and HTN, 10% decrease of total cholesterol level and BP lead to 45% decrease in 
the risk of cardiovascular complications [13].   
Benefits of combined approach to antihypertensive and lipid-lowering treatment was proven in 
ASCOT LLA trial. According to the design of the study patients receiving antihypertensive 
treatment were further randomly assigned to atorvastatin 10 mg daily or placebo. The study was 
stopped prematurely after a median 3.3-year follow-up because of a 36%  statisticially significant 
relative risk reduction (RRR) in non-fatal myocardial infarction and fatal CHD (the primary 
outcome) in favour of atorvastatin and a statisticially significant RRR in fatal and non-fatal stroke  
(27%), total CV events (21%)  and total coronary events (29%) [17].  Following the addition of 
atorvastatin to amlodipine-based treatment with or without perindopril, the relative risk of non-
fatal MI and of fatal CHD decreased by 53% (p<0.001), whereas that of all cardiovascular events 
and of revascularization procedures by 27% (both p = 0.001) after 3.3 years of treatment. By 
contrast, adding atorvastatin to an alternative antihypertensive combination (atenolol ± 
bendroflumethiazide) did not achieve any significant reduction of these clinical endpoints [21]. 
Blood pressure and lipid-lowering effectiveness of a triple fixed combination of  atorvastatin, 
perindopril and amlodipine, administered in various dose combinations, was evaluated in a 3-
month , prospective, multicentre, observational, non-interventional study. After 3 months of 

therapy mean office blood pressure decreased from 158.5 ± 16.7/ 91.7 ± 9.4 to 132.2 ± 8.3/80.1 ± 
6.8 mmHg (p<0.0001), whereas mean 24-h blood pressure decreased from 146.0 ± 14.5/82.5 ± 
12.1 to 132.1 ± 13.2/75.6 ± 9.9 mmHg. Total cholesterol level decreased from 6.18 ± 1.15 to 5.16 
± 0.88 mmol/l and LDL-С - from 3.41 ± 1.01 to 2.80 ± 0.82 mmol/l and triglyceride level from 
2.26 ± 1.17 to 1.82 ± 0.83 mmol/l (all p<0.0001) [16]. 
 According to the results of the epidemiological studies in Russia only 20% of  patients with HTN 
achieve target level of BP and only 17.4% achieve target level of LDL-C [14,18]. Non-sufficient 
adherence to the prescribed antihypertensive treatment is one of the most important reasons for 
this finding [19]. The use of single pill combinations (SPC)  has been shown to increase  adherence 
to treatment by  29% [22]. According to Russian clinical guidelines the majority of patients with 
HTN require a combination dual treatment from the start. It is clearly stated that SPC should be 
preferred in all cases [15].   
Treatment with the fixed triple combination of atorvastatin, perindopril and  amlodipine might 
take us closer to the optimal therapy for hypertensive patients with hypercholesterolaemia. The 
expected improvement of patient adherence to treatment may result in an increase of the 
percentage of patients who achieve both blood pressure control and the LDL-cholesterol targets 
recommended in guidelines. Moreover, this may translate into the further decline of the risk of 
major cardiovascular events. 
  
1.2 Objectives  
Primary objective is to describe antihypertensive and hypolipidaemic effectiveness of a triple 
single-pill combination of amlodipine, atorvastatin and perindopril at 12 weeks in patients with 
arterial hypertension (HTN) and dyslipidemia in the daily clinical practice. 
Secondary objectives 
• 
To determine the proportion of patients who reached systolic (SBP) and diastolic blood 
pressure (DBP) target goals at weeks 4 and 12 of the observation period respectively. 
• 
To determine the proportion of patients who reached LDL-C target goals at week 12 of the 
observation period.  
• 
To evaluate the quality of life of patients at visit 1 (V1) and  visit 2 (V2)  as compared to 
visit 0 (V0) respectively. 
• 
To evaluate the adherence to treatment with the fixed dose combination (FDC) of 
amlodipine/atorvastatin/perindopril in patients included into the study at V1 and V2 as 
compared to V0.  
• 
To evaluate predictors of reaching BP and LDL-C target goals in the study population.    
 
 
1.3 Study variables 
Primary variables: 
• Mean change from baseline (BL) in SBP and DBP assessed at week 12 of the 
observational period.  
• Mean change from BL in LDL-C assessed at week 12 of the observational period.  

7 
 
 
Secondary variables: 
• 
Mean change from BL in SBP and DBP assessed at week 4 of the observation period.  
• Proportion of the patients aged 18-64 years who reached SBP <140 mm Hg and DBP 
<90 mm Hg at week 4 of the observation period. 
• Proportion of patients aged 18-64 years who reached target SBP <130 and ≥120-mm Hg 
and DBP between 70 and79 mm Hg at week 12 of the observation period.  
• Proportion of patients older than 65 years who reached SBP < 140 mm  Hg and DBP < 
90 mm Hg  at week 4 of the observation period. 
• Proportion of patients older than 65 years who reached SBP ≤139 and ≥ 130 mm Hg and 
DBP between 70 and79 mm Hg at week 12 of the observation period.  
• Proportion of patients at very high CV risk who reached LDL-C decrease ≥ 50% from 
BL and reached target < 1,4 mmol/l (55 mg/dl) or  at week 12 of the observation period.  
• Proportion of patients at high CV risk who reached LDL-C decrease  ≥ 50% from BL 
and reached target LDL-C < 1,8  mmol/l (70 mg/dl) at week 12 of the observation period. 
• Proportion of patients at moderate CV risk who reached target LDL-C < 2,6 mmol/l (100 
mg/dl) at week 12 of the observation period.  
• Proportion of patients at different CV risk who reached both BP and LDC-C targets 
• Proportion of patients aged 18-64 years at very high CV risk who reached SBP <130 and 
≥ 120 mm Hg and DBP between 70 and79 mm Hg at week 12 of the observation period 
in the subgroups of the patients receiving SPC of amlodipine/atorvastatin/perindopril in 
the following dosages  5;20;5 mg and  5;20;10 mg and 5;10;5 mg respectively; 
• Proportion of patients older than 65 years at very high CV risk who reached SBP ≤139 
and ≥ 130 mm Hg and DBP between 70 and79 mm Hg at week 12 of the observation 
period in the subgroups of patients receiving SPC of amlodipine/atorvastatin/perindopril 
in the following dosages  5;20;5 mg and  5;20;10 mg and 5;10;5 mg respectively 
• Proportion of patients at very high CV risk who reached  LDL_C decrease  ≥ 50% from 
BL  and reached target <1,4 mmol/l (55 mg/dl) or at week 12 of the observation period 
in the subgroups of the patients receiving SPC  of amlodipine/atorvastatin/perindopril in 
the following dosages  5;20;5 mg and  5;20;10 mg and 5;10;5 mg respectively; 
• Proportion of patients aged 18-64 years at high CV risk who reached SBP <130 and ≥120  
mm Hg and DBP between 70 and79 mm Hg at week 12 of the observation period in the 
subgroups of patients receiving SPC of amlodipine/atorvastatin/perindopril in the 
following dosages  5;20;5 mg and  5;20;10 mg and 5;10;5 mg respectively; 
• Proportion of patients older than 65 years at high CV risk who reached SBP ≤139 and 
≥130 mm Hg and DBP between 70 and79 mm Hg at week 12 of the observational period 
in the subgroups of patients receiving SPC of amlodipine/atorvastatin/perindopril in the 
following dosages  5;20;5 mg and  5;20;10 mg and 5;10;5 mg respectively; 

• Proportion of patients at high CV risk who reached decrease  of LDL-C from BL ≥ 50%   
and reached target <1,8 mmol/l (55 mg/dl)  at week 12 of the observation period in the 
subgroups of patients receiving SPC of amlodipine/atorvastatin/perindopril in the 
following dosages  5;20;5 mg and  5;20;10 mg and 5;10;5 mg respectively; 
• Proportion of patients aged 18-64 years at moderate CV risk who reached SBP <130 and 
≥120 mm Hg and  DBP between 70 and79 mm Hg at week 12 of observational period in 
the subgroups of patients receiving SPC of amlodipine/atorvastatin/perindopril in the 
following dosages  5;20;5 mg and  5;20;10 mg and 5;10;5 mg respectively; 
• Proportion of patients older than 65 years at moderate CV risk who reached SBP ≤139 
and ≥130 mm Hg and DBP between 70 and 79 mm Hg at week 12 of the observation 
period in the subgroups of patients receiving SPC of amlodipine/atorvastatin/perindopril 
in the following dosages  5;20;5 mg and  5;20;10 mg and 5;10;5 mg respectively; 
•  Proportion of patients at moderate CV risk who reached LDL-C  < 2,6 mmol/l  (100 
mg/dl) at week 12 of the observation period in the subgroups of patients receiving SPC 
of amlodipine/atorvastatin/perindopril in the following dosages  5;20;5 mg and  5;20;10 
mg and 5;10;5 mg respectively;  
• Mean change from V0 in scores of the SF-36 questionnaire assessed at V1 and V2;  
• Proportion of patients with high, moderate and low adherence  to the treatment with SPC 
of amlodipine/atorvastatin/perindopril at V1 as compared to V0 via medication 
adherence scale; 
• Proportion of patients with high, moderate and low adherence to the treatment with SPC 
of amlodipine/atorvastatin/perindopril at V2 as compared to V0 via medication 
adherence scale; 
• Association between the fact of achieving target BP levels at week 12 and  baseline BP 
and LDL-C levels;  
• Association between the fact of achieving target LDL-C level at week 12  and baseline 
BP and LDL-C levels as well as CV risk category;  
• Association between the fact of achieving target BP and LDL-C levels at week 12 with 
the categories of CV risk, initial dosage of SPC amlodipine/atorvastatin/perindopril and 
adherence rate to the administered therapy with FDC.  
• Association between patients’adherence to SPC amlodipine/atorvastatin/perindopril 
therapy at week 4 and week 12 and  baseline BP level. 
• Predictors for achieving target BP levels (i.e. smoking, sex, baseline SBP and DBP, 
duration of HTN,  level of CV risk, duration of therapy,  baseline LDL-C level, CAD 
diagnosis);  
• Predictors for achieving target LDL-C levels (i.e. smoking, sex,baseline  SBP and DBP, 
duration of HTN,  level of CV risk, duration of therapy, baseline LDL-C level, CAD 
diagnosis). 
 

9 
 
2. Methods and documentation  
2.1   Study design with the rationale for its’ choice  
This is a multi-centre, observational, ambispective study, which will retrospectively and 
prospectively collect clinical and socio-demographic data from medical records of patients with 
HTN and dyslipidemia initiated with SPC of amlodipine/atorvastatin/perindopril in real clinical 
settings.  
For parameters of the primary end-point such as BP and LDL-C a Baseline data is defined  as 
values of these parameters present in medical records at the nearest date preceding the start of SPC 
amlodipine/atorvastatin/perindopril.  Therefore BP and LDL-C Baseline data will be collected 
retrospectively from medical records of patients with HTN and dyslipidemia. To be included in 
the study for further prospective observation a patient should have been administered with SPC of 
amlodipine/atorvastatin/perindopril within one month before the Index Date. The Index date is a 
date when a decision to include a patient in the study for further 12 week prospective observation 
made by a treating physician after evaluation of recorded data to confirm patient’s eligibility for 
the study.  Once an investigator makes sure that a patient meets all inclusion/non-inclusion critera   
the investigator will discuss with the patient during his/her next visit and obtain the signed patient’s 
informed consent to participate in the study (V0).   
 SPC of amlodipine/atorvastatin/perindopril will be administered to the patients in accordance to 
the instruction for medical use approved in the Russian Federation.  Decision on this medicinal 
product administration will not be dependent on the decision to include a patient into the 
observational study and according to the study protocol, such decision should precede treating 
investigator’s intention to include a patient in the study.     
 
 
2.2  Calculation of the sample size 
 
In the clinical study superiority hypothesis over baseline will be assessed. 
The parameters of SBP, DBP and LDL-cholesterol are quantitative and changes between 12 weeks 
and baseline will be made, therefore, for the sample size calculation was used the following 
formula: 
𝑛= 𝜎2(𝑍1−𝛼+ 𝑍1−𝛽)2
(µ𝐴− µ0 − δ)2  
To calculate the sample size were used the following articles: 
• 
Dézsi, C. A. (2018). Treatment with triple combination of atorvastatin, perindopril, and 
amlodipine in patients with stable coronary artery disease: A subgroup analysis from the 
PAPA-CAD study. Journal of International Medical Research, 46(5), 1902-1909. 

• 
Simon, A., & Dézsi, C. A. (2019). Treatment of hypertensive and hypercholesterolaemic 
patients with the triple fixed combination of atorvastatin, perindopril and amlodipine: the 
results of the CORAL study. Advances in therapy, 36(8), 2010-2020. 
Systolic blood pressure 
According to the literature the following assumptions were made: 
• 
Study drug efficacy (µ𝐴) – mean systolic blood pressure after 3 month of therapy will be 
132.2 mmHg.  
• 
Null hypothesis drug efficacy (µ0) - mean systolic blood pressure will be the same as at 
baseline – 158.5 mmHg.  
• 
Maximum Standard deviation (σ) – 16.7 mmHg. 
• 
Superiority margin (δ) considered as half of the difference between the drug and baseline – 
-13.15 mmHg (D'Agostino Sr R. B., Massaro J. M., Sullivan L. M. Non‐inferiority trials: 
design concepts and issues–the encounters of academic consultants in statistics //Statistics 
in medicine. – 2003. – Т. 22. – №. 2. – С. 169-186.; Food and Drug Administration et al. 
Non-inferiority clinical trials to establish effectiveness: guidance for industry //US 
Department of Health and Human Services. – 2016.; Committee for Proprietary Medicinal 
Products (CPMP et al. Points to consider on switching between superiority and non-
inferiority //British journal of clinical pharmacology. – 2001. – Т. 52. – №. 3. – С. 223.). 
• 
Type I error (α) – 1%. 𝑍1−𝛼 – 2,326. 
• 
Type II error (β) – 10%. 𝑍1−𝛽 – 1.282. 
The null hypothesis is formulated as: 
“Change in mean systolic blood pressure after 3 month of therapy comparing to baseline will be 
not less than -13.15 mmHg” 
𝐻0: µ𝐴− µ0 ≥−13.15 
The alternative hypothesis is formulated as: 
“Change in mean systolic blood pressure after 3 month of therapy comparing to baseline will be 
less than -13.15 mmHg” 
𝐻1: µ𝐴− µ0 < −13.15 
As a result of the calculation, it was found that in order to obtain statistically significant results, it 
is necessary to use data from at least 21 completed cases.  
Diastolic blood pressure 
According to the literature the following assumptions were made: 
• 
Study drug efficacy (µ𝐴) – mean diastolic blood pressure after 3 month of therapy will be 
80.1 mmHg.  
• 
Null hypothesis drug efficacy (µ0) - mean diastolic blood pressure will be the same as at 
baseline – 91.7 mmHg.  
• 
Maximum Standard deviation (σ) – 9.9 mmHg. 
• 
Superiority margin (δ) considered as half of the difference between the drug and baseline – 
-5.8 mmHg (D'Agostino Sr R. B., Massaro J. M., Sullivan L. M. Non‐inferiority trials: 

11 
 
design concepts and issues–the encounters of academic consultants in statistics //Statistics 
in medicine. – 2003. – Т. 22. – №. 2. – С. 169-186.; Food and Drug Administration et al. 
Non-inferiority clinical trials to establish effectiveness: guidance for industry //US 
Department of Health and Human Services. – 2016.; Committee for Proprietary Medicinal 
Products (CPMP et al. Points to consider on switching between superiority and non-
inferiority //British journal of clinical pharmacology. – 2001. – Т. 52. – №. 3. – С. 223.). 
• 
Type I error (α) – 1%. 𝑍1−𝛼 – 2,326. 
• 
Type II error (β) – 10%. 𝑍1−𝛽 – 1.282. 
The null hypothesis is formulated as: 
“Change in mean diastolic blood pressure after 3 month of therapy comparing to baseline will be 
not less than -5.8 mmHg” 
𝐻0: µ𝐴− µ0 ≥−5.8 
The alternative hypothesis is formulated as: 
“Change in mean diastolic blood pressure after 3 month of therapy comparing to baseline will be 
less than -5.8 mmHg” 
𝐻1: µ𝐴− µ0 < −5.8 
As a result of the calculation, it was found that in order to obtain statistically significant results, it 
is necessary to use data from at least 38 completed cases.  
LDL-cholesterol 
According to the literature the following assumptions were made: 
• 
Study drug efficacy (µ𝐴) – mean LDL-cholesterol level after 3 month of therapy will be 
2.65 mmol/L.  
• 
Null hypothesis drug efficacy (µ0) - mean LDL-cholesterol level will be the same as at 
baseline – 3.09 mmol/L.  
• 
Maximum Standard deviation (σ) – 1.01 mmol/L. 
• 
Superiority margin (δ) considered as half of the difference between the drug and baseline – 
-0.22 mmol/L (D'Agostino Sr R. B., Massaro J. M., Sullivan L. M. Non‐inferiority trials: 
design concepts and issues–the encounters of academic consultants in statistics //Statistics 
in medicine. – 2003. – Т. 22. – №. 2. – С. 169-186.; Food and Drug Administration et al. 
Non-inferiority clinical trials to establish effectiveness: guidance for industry //US 
Department of Health and Human Services. – 2016.; Committee for Proprietary Medicinal 
Products (CPMP et al. Points to consider on switching between superiority and non-
inferiority //British journal of clinical pharmacology. – 2001. – Т. 52. – №. 3. – С. 223.). 
• 
Type I error (α) – 1%. 𝑍1−𝛼 – 2,326. 
• 
Type II error (β) – 10%. 𝑍1−𝛽 – 1.282. 
The null hypothesis is formulated as: 

“Change in mean LDL-cholesterol level after 3 month of therapy comparing to baseline will be 
not less than -0.22 mmol/L” 
𝐻0: µ𝐴− µ0 ≥−0.22 
The alternative hypothesis is formulated as: 
“Change in mean LDL-cholesterol level after 3 month of therapy comparing to baseline will be 
less than -0.22 mmol/L” 
𝐻1: µ𝐴− µ0 < −0.22 
As a result of the calculation, it was defined that in order to obtain statistically significant results, 
it is necessary to use data from at least 274 completed cases.  
To obtain statistically significant results on all three primary endpoints the greatest value of 
calculated sample size was chosen – 274 completed cases. 
Taking into account the possible drop-out rate of 30% of patients during the study, 400 patients 
should be included in the study. 
2.3 Selection of doctors 
A total of 80 general practitioners and outpatient cardiologists will participate in this non-
interventional study 
2.4 Selection of patients 
2.4.1 Inclusion criteria  
 Obtained signed informed consent from the patient 
 Patients of 18 years and older and younger than 80 years. 
 Start of the treatment with SPC of amlodipine/atorvastatin/perindopril within 1 month from 
the Index date in accordance with the indication in Russian SmPC. 
 Presence of the parameters of interest* in the medical records dated with the nearest to the 
start of  SPC amlodipine/atorvastatin/perindopril treatment date.  
 
* Parameters of interest include measured at rest office BP and LDL-C.   
  2.4.2 Non-inclusion criteria 
 Subjects who are unwilling or unable to provide a signed informed consent form; 
 Any contraindication to the treatment with the SPC of amlodipine/atorvastatin/perindopril 
according to its’ approved  instruction for medical use in the Russian Federation; 
 Concomitant use of any other ACE inhibitors, CCBs, ARBs and statins.  
 Supposed low treatment  adherence to the assigned SPC and the risk for poor collaboration 
between the patient and  the investigator during the study; 
 Any severe, decompensated or unstable somatic diseases or states that according to 
investigator discretion are life-threatening or worsen the prognosis for the patient: 
myocardial infarction in the past 3 months, unstable angina, current  decompensation of 
diabetes mellitus, autoimmune or oncological diseases, severe cardiac arrhythmia, 

13 
 
gastrointestinal disorders affecting absorbtion, severe hepatic diseases, pancreatic diseases, 
severe allergic reactions, connective tissue diseases etc; 
 Secondary arterial hypertension; 
 Alcohol or any drug abuse; 
 Surgical intervention on heart or coronary vessels  (i.e., heart valve(s) replacement, stent 
implantation or CABG), or any non-cardiological serious surgical intervention that are 
planned within next 3 months and may require withdrawal or changes in current therapy; 
 Glomerular filtration rate less than 60 ml/min/1,72m2; 
 Participating in any other clinical trial currently or during 30 days  period before informed 
consent was signed. 
 
2.5 Therapeutic strategy during the study  
2.5.1 Treatment with the studied drug  
Amlodipine 5 mg + atorvastatin 10 mg + perindopril arginine  5 mg 
Amlodipine 5 mg + atorvastatin 20 mg + perindopril arginine 5 mg 
Amlodipine 5 mg + atorvastatin 20 mg + perindopril arginine 10 mg 
 
This is non-interventional study that is observational by its nature. Therefore there will be no any  
assignments of subjects to a particular therapeutic strategies defined by this protocol. Decision to 
treat a patient with SPC of amlodipine/ atorvastatin/ perindopril should be at the descretion of a  
treating investigator and made in accordance to local standards and protocols.  
2.5.2 Concomitant drugs 
Due to the non-interventional design of the study, it is allowed to use any concomitant treatments 
or drugs if it is considered necessary by the treating invstigator. Any changes in the medical 
treatment are also allowed during the observational period of the study and will be gathered and 
appropriately reflected in the study documentation at appointed visits to clinics by a treating 
investigator.  
2.6 Duration of non-interventional study 
It is planned to complete enrolment of patients in this non-intervention study within 6 months. 
Follow-up period for each patient will be 12 weeks.  
First patient in is scheduled for Q4 2022 
Last patient in is scheduled for Q2 2023 
Last patient last visit Q3 2023 

Data base lock is scheduled for Q3 2023 
Statistical analysis is scheduled for Q4 2023 
Clinical study report is scheduled for Q1 2024 
 
2.7 Documentation of the non-interventional clinical study 
2.7.1. Documentation folder 
Each doctor will be provided with a documentation folder containing a complete set of documents 
for 5-6 patients + 2 extra sets in case of lost or damage of study documentsincluding:  
• 
One protocol of the observation plan; 
• 
Documents for 5-6 patients (12 Patient Informed Consent Forms, with 5-6 Adverse 
event/adverse drug reaction/special situation reporting forms). 
• 
2 extra sets in case of lost or damage of study documents (Patient Informed Consent Form,; 
Adverse event/adverse drug reaction/special situation reporting forms) 
2.7.2 Study schedule and plan 
According to the design of this multicentre, non-intervention, observational study in patients with 
HTN and dyslipidemia treated with SPC of amlodipine/atorvastatin/perindopril, three visits will 
be appointed to include patients and to gather parameters of interest to describe treatment 
effectiveness and safety of the FDC. 
Following visits will be appointed: 
1. Inclusion Visit 0  (V0) – month 0; 
2. Follow up Visit 1 (V1) – 4 weeks after  V0; 
3. Final Visit 2 (V2): 12 weeks after V0;  
 
Table 1 – Planned study visits  
Procedure 
Retrospective 
evaluation of 
patient’s eligibility  
Inclusion  
Visit 0 
Month 0 
Follow up visit 
V1 
 ( 4 weeks ± 2 
weeks)  
Final visit  
V2 
(12 weeks ± 2 
weeks) 
Written informed consent 
 
× 
 
 
Assessment in accordance with 
inclusion/ non-inclusion critera  
× 
× 
 
 
Demographics 
 
× 
 
 
Risk factors and life style 
 
× 
 
 
Cardio-vascular disease history 
 
× 
 
 
Physical examination with the 
measurement of BP at rest  
 
× 
× 
× 

15 
 
LDL-C 
 
× 
 
× 
Current treatment with 
concomitant cardiovascular 
medications/ changes and reasons 
 
× 
× 
× 
Current treatment with other 
concomitant medications  
 
× 
× 
× 
Medication adherence scale 
 
× 
× 
× 
Quality of life evaluation  (SF-36) 
 
× 
× 
× 
Treatment with the SPC  
amlodipine/atorvastatin/perindopril 
status  
 
× 
× 
× 
SPC  
amlodipine/atorvastatin/perindopril 
dosage correction (if occured) 
 
× 
× 
× 
Adverse events/drug reactions/ 
special situations reporting  
 
× 
× 
× 
 
2.7.4. Data collection: 
Data evaluation during the screening period: 
HCPs participating in the study will conduct a retrospective analysis of patient’s records for the 
purpose of evaluating patient’s eligibility to be enrolled in the study. Patients with HTN and 
dyslipidemia who had been initiated with SPC amlodipine/atorvastatin/perindopril within one  
month before the Index Date   and who meet other inclusion / non inclusion criteria will be included 
in the study if they sign a consent form at the inclusion visit.  
 Data collection at the inclusion visit (V0): 
 
• 
Obtaining patient informed consent; 
• 
Checking for inclusion/non-inclusion criteria; 
• 
Demographics, CVD history, cardiovascular risk factors (appendix 8) 
• 
Physical examination and vital signs (BP); 
• 
Current status of taking SPC amlodipine/atorvastatin/perindopril and dose regimen; 
• 
SBP, DBP and LDL-C according to the medical records dated with the nearest to the start 
of treatment with SPC amlodipine/atorvastatin/perindopril; 
• 
Concomitant current use of  any other cardiovascular medications (i.e. antihypertensive, 
anti-ischaemic, anti-platelet, anticoagulant medications) and any other concomitant 
medications 
• 
Baseline assessment of adherence to SPC amlodipine/atorvastatin/perindopril done by 
medication adherence scale; 

• 
Quality of life assessment (questionnaire SF-36) 
• 
Adverse events/drug reactions/special situations 
 
Data collection at the Follow up Visit (V1): 
• 
Physical examination and vital signs (BP); 
• 
Current status of taking SPC amlodipine/atorvastatin/perindopril and dose regimen 
correction if needed; 
• 
Assessment of adherence to SPC amlodipine/atorvastatin/perindopril done by medication 
adherence scale; 
• 
Quality of life assessment (questionnaire SF-36) 
• 
Concomitant current use of other cardiovascular medications and any other medications 
• 
Adverse events/drug reactions/special situations 
 
Data collection at the Final Visit  (V2): 
• 
Physical examination and vital signs (BP); 
• 
Current status of taking SPC amlodipine/atorvastatin/perindopril and a dose regimen 
correction if needed; 
• 
LDL-C assessment; 
• 
Assessment of adherence to SPC amlodipine/atorvastatin/perindopril done by medication 
adherence scale; 
• 
Quality of life assessment (questionnaire SF-36) 
• 
Concomitant current use of other cardiovascular medications and any other medications 
• 
Adverse events/drug reactions/special situations 
 
 

17 
 
Figure 1. The scheme of TARGET study 
2.7.5 Implementation of non-intervention study  
The treating investigator will receive a documentation folder and instructions from the Servier 
staff. The patient should be informed of his/her participation in this study and the transfer of his/ 
her clinical data from the site to the responsible professional subcontractor for statistical analyses. 
Written informed consent must be obtained from the patient at the inclusion visit.. In case of 
occurrence of adverse events (AEs), adverse drug reactions (ARDs), or special situations, it is 
necessary to follow the requirements listed in the section «Responsibilities of the investigator». 
Please hand over the folder with the complete documentation to your Servier local executive. 
Patients will undergo clinical assessment and receive the standard medical care as usual 
determined by the treating doctors based on their clinical judgement and national guidelines. 
Patients will not receive experimental treatment as a consequence of their participation in the 
observational study 
3  Pharmacovigilance 
3.1 Definitions 
3.1.1 Pharmacovigilance information  
Pharmacovigilance data include any unintended or adverse event associated with the use of a 
medicinal product in humans, whether or not considered drug related, including the following 
special situations (situations where no adverse event occurred but information needs to be 
collected):  
• 
exposure during pregnancy or breastfeeding;  
• 
overdose, abuse, misuse, off-label uses, medication error, or occupational exposure 
(including professional one); 
• 
lack of treatment effectiveness of a medicinal product; 
• 
any suspected transmission via medicinal product of an infection agent;  
• 
unintended therapeutic benefit.  
 
 3.1.2 Adverse Event (AE)  
Adverse event is any untoward medical occurrence in a patient or a clinical-trial subject who 
received the medicinal product, which does not necessarily have a causal relationship with the use 
of this medicinal product. 

An adverse event can therefore be any unfavourable and unintended sign (e.g. an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product. 
3.1.3 Adverse (drug) reaction (ADR)  
Adverse reaction (synonyms: Adverse drug reaction, Suspected adverse (drug) reaction, Adverse 
effect, Undesirable effect) is a response to a medicinal product which is noxious and unintended.  
“Response” in this context means that a causal relationship between a medicinal product and an 
adverse event is at least a reasonable possibility.  
Adverse reactions may arise from use of the product within or outside the terms of the marketing 
authorization or from occupational exposure. Conditions of use outside the marketing 
authorization include off-label use, overdose, misuse, abuse and medication errors. 
 3.1.4 Serious adverse (drug) reaction (SADR) 
Serious adverse reaction is an adverse reaction, which results in death, is life-threatening, requires 
in-patient hospitalisation or prolongation of existing hospitalisation, results in persistent or 
significant disability or incapacity, or is a congenital anomaly/birth defect. 
“Life threatening” in this context refers to a reaction in which the patient was at risk of death at 
the time of the reaction; it does not refer to a reaction that hypothetically might have caused death 
if more severe. 
Medical and scientific judgement should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalisation but might jeopardise the patient or might require 
intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation or development 
of dependency or abuse. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
3.2 Responsibilities  
 3.2.1 Events to be reported  
All available information about the following reported events occurring during the study will be 
recorded. All reported AEs/ADRs will be described in the statistical analysis report.  
• All serious adverse drug reactions related to the use of  amlodipine/atorvastatin/perindopril 
FDC; 
• All 
non-serious 
adverse 
drug 
reactions 
related 
to 
the 
use 
of 
SPC 
amlodipine/atorvastatin/perindopril); 
• All reports about special situations (see 3.1.1); 

19 
 
• All adverse events 
3.2.2 Responsibilities of the investigator 
At the visits during the study,the treating physician will ask the participating patient to indicate 
whether or not an adverse event (serious or not) has occurred. 
The treating physician should determine the presence/absence of a causal relationship between the 
use of the study drug and the adverse event, the presence/absence of criteria for seriousness, and 
then the outcome of the event. 
In case of detection of any adverse event/adverse drug reaction or occurrence of a special situation 
during the study (both serious or not serious), the treating physician must fill out the «Adverse 
event/adverse drug reaction/special situation reporting form» (Appendix No.4) without waiting 
for the clinical outcome or the results of additional investigations. 
If the event is serious, the form should be sent immediately (same or next working day at the latest) 
to Servier company in Russia via e-mail to address pvmail.rus@servier.com or by fax to number 
(495) 937-47-66. The anonymized copies of all the available and relevant laboratory findings, 
hospitalisation reports or other investigation results performed in relation to the adverse event 
should be attached to the form. All other events should be transmitted by the treating physician 
within 2 working days. 
The same obligations will apply for follow-up reports. The treating physician must ensure that 
follow-up of the participant is appropriate to the nature of the event, and that it continues until 
resolution. She/he will continue to notify follow up data according to timeframes defined 
above. 
If the follow-up of the participant is not done by the treating physician him/herself 
(hospitalisation, followed by a specialist or the participant's general practitioner,…), the 
treating physician will do every effort to establish/maintain contact with the 
person/department in charge of follow-up of the participant, so as to have additional 
information and report it. 
 3.2.3 Responsibilities of the Sponsor/Marketing Authorisation Holder 
Independently of the regulatory obligations of investigator, the sponsor/marketing authorisation 
holder (MAH) must report the pharmacovigilance data to the appropriate authorities in accordance 
with the Good PharmacoVigilance Practice and local regulations. 
Cases of adverse event are considered to be closed when the patient has recovered or his/her 
condition was stabilised, providing that the available data are sufficiently detailed for adequate 
medical analysis of the case. 

4 Data management, quality management, statistics and reporting 
4.1 Data management 
Data collection in this study is carried out using documentation forms. Centralized data entry will 
be carried out by a responsible professional subcontractor for statistical analyses after receiving 
documentation forms. Statistical analysis of the data and the creation of the final statistical report 
on the study will also be carried out by the responsible professional subcontractor for statistical 
analyses. 
4.2 Statistical analysis 
Due to the non-interventional nature of this study, statistical analysis will be carried out in 
descriptive and exploratory forms. All parameters will be analysed using descriptive statistics. For 
each parameter, the following will be specified: number of patients, mean value, standard error, 
minimum and maximum values, or proportion of each category. All composite endpoints will be 
listed and presented in visual form as graphs and in tables of parameters and their frequencies. For 
categorical variables, absolute values and rates in per cents be calculated. The calculations of 
relative rates will include only patients in whom values of the corresponding variables will be 
available.  
Accepted level of significance 
In all tests, a significance level of 0.05 will be used, and 2-sided statistical tests will be carried out. 
Search statistical analysis will be performed in the following subgroups of patients:   
- patients with stable CAD 
- patients with diabetes mellitus type 1 or type 2 
- patients with chronic kidney disease     
All reports of adverse drug reactions (ARDs), adverse events (AEs), serious ADR/AE, and special 
situations will be encoded using MedDRA by the subcontractor , and the results will be listed and 
classified according to the System-Organ-Classes (SOCs). Descriptive statistics will be used. 
4.3 Report preparation 
The preparation of the final report on the study will begin after the completion of the statistical 
analysis. The publication of the main results is planned within 12 months after the end of the study. 
5. Ethical considerations 
The study will be carried out in accordance with the principles of the Helsinki Declaration, 
according to the version revised in Brazil in 2013. The protocol must be reviewed and approved 
by an independent ethics committee after it is submitted by the coordinator or sponsor in 
accordance with local regulatory requirements, especially on the matters relating to data 
protection. Patients will be informed about the conditions for participation in the study, and they 
will have to provide written consent to participate in the study. The doctor must confirm in the 
Case report form (CRF) that the informed consent has been obtained, and he/she must keep one 

21 
 
original of the signed informed consent form in the patient’s file. “Informed consent” also means 
an individual discussion of procedures, that will be conducted as a part of the study, with the 
patient.  
5.1 Patient data privacy  
Investigators should maintain confidentiality of information about patients included in this study. 
Confidential data should contain enough information to contact the patient in case of emergency, 
or if further monitoring is required. Patient's right to privacy is of utmost importance. To protect 
the data confidentiality and preserve patient anonymity, patient’s identity will be encoded in the 
study documentation. Patients can be identified using a unique number, age and gender, which 
will be recorded in the CRF. To reveal the patient’s identity, all investigators will keep a 
confidential list for patient identification containing the names and addresses of the patients, as 
well as their assigned numbers. Thus, only investigator will be able to decode the identity of a 
patient. 
 
6. Appendices 
Appendix 1. Classification of blood pressure and definition of hypertension 
grade [15]. 
BP categories  
SBP, mm Hg 
 
DBP, mm Hg 
Optimal 
<120 
and 
<80 
Normal  
120–129 
and/or 
80–84 
High normal 
130–139 
and/or 
85–89 
Grade 1 
140–159 
and/or 
90–99 
Grade 2 
160–179 
and/or 
100–109 
Grade 3 
≥180 
and/or 
≥110 
Isolated systolic 
hypertension1 
≥140 
and 
<90 
1 Isolated systolic hypertension (ISH) should be classified into grades 1, 2, and 3 according to the 
SBP level.  
 
 
 
 
 
 
 

 
 
 
 
 
Appendix 2.  
Medication Adherence Scale [20]. 
1. Sometimes I can make a break in my daily medication therapy for: 
a) One day 
b) Two days 
c) Three days 
d) I don’t make breaks at all 
2. I take my medications: 
a) Every day 
b) Only when I feel unwell 
c) I take courses of medication treatment 
d) In exceptional cases 
3. I change dosage/frequency of medication administered by the doctor: 
a) I start taking medications as administered and then I change as I feel appropriate 
b) I make the dosage lower when I feel better 
c) I change the dosage (make it higher or lower) depending on the way I feel  
d) I take the dosage administered by the doctor independently of how I feel 
4. I stop taking medication when: 
a) I feel that I am not sick anymore 
b) I don’t feel pain or discomfort anymore 
c) Medication is withdrawn by the doctor 
d) Medication doesn’t help me  
 
Appendix  3.  
The SF-36 health survey questionnaire  
(The survey was developed by RAND Health on the basis of Medical Outcomes Study; the 
Russian version was developed and recommended by the Multinational Center for Quality of 
Live Research) 
Name of patient __________________ 
Date of completion ________________  
 
 
Please circle one number for each statement. 
 
1. In general, would you say your health is? 
Excellent  ................................................................... 1 

23 
 
Very good ................................................................. 2 
Good ......................................................................... 3 
Fair ............................................................................ 4 
Poor  .......................................................................... 5 
 
2. Compared to one year ago, how would you rate your health in general now? 
Much better now than one year ago......................... 1 
Somewhat better now than one year ago ………… 2 
About the same ........................................................ 3 
Somewhat worse now than one year ago……….... 4 
Much worse now than one year ago ……………….5 
 
3. The following items are about activities you might do during a typical day. Does your 
health now limit you in these activities? If so, how much? 
 
Yes, limited a 
lot 
Yes, limited a 
little 
No, not 
limited at 
all 
A. Vigorous activities, such as running, lifting 
heavy objects, participating in strenuous sports. 
1 
2 
3 
B. Moderate activities, such as moving a table, 
pushing a vacuum cleaner, bowling, or playing 
golf. 
1 
2 
3 
C. Lifting or carrying groceries. 
1 
2 
3 
D. Climbing several flights of stairs. 
1 
2 
3 
E. Climbing one flight of stairs. 
1 
2 
3 
F. Bending, kneeling, or stooping. 
1 
2 
3 
G. Walking more than a mile. 
1 
2 
3 

H.   Walking several blocks. 
1 
2 
3 
I. Walking one block. 
1 
2 
3 
J. Bathing or dressing yourself. 
1 
2 
3 
 
4. During the past 4 weeks, have you had any of the following problems with your work or 
other regular daily activities as a result of your physical health: 
 
Yes  
No 
A. Cut down the amount of time you spent on work or other 
activities. 
1 
2 
B. Accomplished less than you would like. 
1 
2 
C. Were limited in the kind of work or other activities. 
1 
2 
D. Had difficulty performing the work or other activities (for 
example, it took extra effort). 
1 
2 
 
5. During the past 4 weeks, have you had any of the following problems with your work or 
other regular daily activities as a result of any emotional problems (such as feeling depressed 
or anxious)? 
 
Yes  
No 
А. Cut down the amount of time you spent on work or other 
activities. 
1 
2 
B. Accomplished less than you would like. 
1 
2 
C. Didn't do work or other activities as carefully as usual. 
1 
2 
 
6. During the past 4 weeks, to what extent has your physical health or emotional problems 
interfered with your normal social activities with family, friends, neighbors, or groups? 
 
Not at all ..........................................................  1 
Slightly ............................................................ 2 
Moderately ....................................................... 3 

25 
 
Quite a bit ........................................................ 4 
Extremely ........................................................ 5 
 
7. How much bodily pain have you had during the past 4 weeks? 
None ................................................................ 1 
Very mild ......................................................... 2 
Mild ................................................................. 3 
Moderate .......................................................... 4 
Severe  ............................................................. 5 
Very severe ………………...……………………6 
 
8. During the past 4 weeks, how much did pain interfere with your normal work (including 
both work outside the home and housework)? 
Not at all .......................................................... 1 
A little bit ......................................................... 2 
Moderately ....................................................... 3 
Quite a bit ........................................................ 4 
Extremely ........................................................ 5 
 
9. These questions are about how you feel and how things have been with you during the past 
4 weeks. For each question, please give the one answer that comes closest to the way you have 
been feeling. How much of the time during the past 4 weeks... 
 
All of 
the time 
Most of 
the time 
A good 
bit of 
the time 
Some 
of the 
time 
A little 
of the 
time 
None 
of the 
time 
A. Did you feel full of pep? 
1 
2 
3 
4 
5 
6 
B. Have you been a very 
nervous person? 
1 
2 
3 
4 
5 
6 

C. Have you felt so down in the 
dumps that nothing could cheer 
you up? 
1 
2 
3 
4 
5 
6 
D. Have you felt calm and 
peaceful? 
1 
2 
3 
4 
5 
6 
E. Did you have a lot of 
energy? 
1 
2 
3 
4 
5 
6 
F. Have you felt downhearted 
and blue? 
1 
2 
3 
4 
5 
6 
G. Did you feel worn out? 
1 
2 
3 
4 
5 
6 
H. Have you been a happy 
person? 
1 
2 
3 
4 
5 
6 
I. Did you feel tired? 
1 
2 
3 
4 
5 
6 
 
10. During the past 4 weeks, how much of the time has your physical health or emotional 
problems interfered with your social activities (like visiting with friends, relatives, etc.)? 
All of the time .................................................. 1 
Most of the time ............................................... 2 
Some of the time .............................................. 3 
A little of the time …………………..……… 4  
None of the time .............................................. 5 
 
 
 

27 
 
11. How TRUE or FALSE is each of the following statements for you? 
 
Definitely 
true 
Mostly 
true 
Don't 
know 
Mostly 
false 
Definitely 
false 
A. I seem to get sick a little easier 
than other people 
1 
2 
3 
4 
5 
B. I am as healthy as anybody I know 
1 
2 
3 
4 
5 
C. I expect my health to get worse 
1 
2 
3 
4 
5 
D. My health is excellent 
1 
2 
3 
4 
5 
 
 
The survey has the following scales: 
1. Physical functioning (PF). 
2. Role physical (RР). 
3. Bodily pain (BP). 
4. General health (GH). 
5. Vitality (VT). 
6. Social functioning (SF). 
7. Role emotional (RE). 
8. Mental health (MH). 
 
All the scales of survey constitute two composite measurements: Physical Component Summary 
(PCS) (scales 1 to 4) and Mental Component Summary (MCS) (scales 5 to 8). 
 
The method for calculating the main parameters of the SF-36 questionnaire 
Scale 
Questions 
Minimal and 
maximal values 
Possible range of 
values 
1. Physical functioning 
(PF) 
3A, 3B, 3C, 3D, 3E, 3F, 
3G, 3H, 3I, and 3J 
10 – 30 
20 
2. Role physical (RР) 
4A, 4B, 4C, and 4D 
3 – 8 
4 
3. Bodily pain (BP) 
7 and 8 
2 – 12 
10 

4. General health (GH) 
1, 11A, 11B, 11C, and 
11D 
5 – 25 
20 
5. Vitality (VT) 
9A, 9E, 9G, and 9I 
4 – 24 
20 
6. Social functioning (SF) 
6 and 10 
2 – 10 
8 
7. Role emotional (RE) 
5A, 5B, and 5C. 
3 - 6 
3 
8. Mental health (MH) 
9B, 9C, 9D, 9F, 9H. 
5 – 30 
25 
 
For items 6, 9A, 9E, 9D, 9H, 10, and 11, the count-down is applied. 
The 
formula 
for 
calculating 
the 
values:  
[ (actual value of the scale) – (minimal possible value on the scale] : (possible range of values) 
 
100. 
Requirements for presenting the results:  
1. Number of cases per each parameter should be indicated;  
2. Descriptive statistics: M ± SD, Me (LQ; UQ), % (n/N);  
3. Accuracy of results (estimates, Р value); Confidence interval (for main results of the study) 
and Р value;  
4. Statistical methods (parametric and non-parametric) and statistical packages should be 
mentioned.  
 
The recommended statistical packages for the data processing are StatSoft Statistica v.6.0, and 
SPSS 9.0. 
 
 
 
 
 
 
 
 
 
 

29 
 
Appendix 4. Adverse event / Adverse drug reaction / Special Situation 
Reporting Form 
 
 
TARGET  
Protocol № IC4-05351-070-RUS  
Please send this form immediately by fax (495) 937-47-66 or by email to pvmail.rus@servier.com, 
or pass it to the associate of the company. 
Year of birth   or   Age           Gender 
 Height 
 Weight 
     Patient number 
 
|_|_|_|_|            or   |_|_|_|          M / F 
   |_|_|_| 
     |_|_|_| 
        |_|_|_|_|_|_|_|_|_|_| 
     
Observed adverse event: 
 Date of onset  
 
|_|_|  |_|_|  |_|_|_|_| 
 Until (if recovered) 
 
|_|_|  |_|_|  |_|_|_|_| 
 
 
 
Serious: 
 No 
 
 Yes, because: (please choose below)  
 
 
 Fatal 
 
 Life-threatening  
 
 Hospitalisation or prolongation of hospitalisation  
 
 Persistent or significant disability or incapacity  
 
 Congenital anomaly/birth defect 
 
 Medically significant 
Outcome: 
 
 Recovered   
 
 Recovered with sequelae 
 
 Recovering   
 
 Not recovered 
 
 Fatal   
 
 Unknown 
General disease(s) / Concomitant disease(s) (please indicate year of first diagnoses):  
 
Course (please enclose relevant findings e.g. laboratory, hospital reports, histology, etc.): 
 
 
 

Causal relationship with the studied Servier drug: 
⁬ 
 No 
  
 Yes  
 Not applicable 
 
If yes, please specify dates of treatment with the studied drug in the table below on the first line:  
 
If no or not applicable, please indicate whether the adverse event /special situation is related to a Servier medicinal 
product (as mentioned in the following table): 
  
 No 
  
 Yes please specify which Servier medicinal product: ………………………………. 
Medication list 
Daily dosage / 
application 
Administered 
Indication 
 
 
- 
 
 
 
 
 
 
 
- 
 
 
 
- 
 
 
 
 
 
Name:  
Speciality:  
Address: 
Phone: 
 
Date:                                                           
 
 
Signature: 
Special situations*: situations where no adverse events occurred but information needs to be collected: exposure during pregnancy 
or breastfeeding, abuse, misuse, medication error, overdose, off label use, occupational exposure, lack of efficacy, suspected 
transmission of infectious agent via a medicinal product, unintended therapeutic benefit …  
Appendix 5.  Score Scale 
Name: SCORE scale (Systematic Coronary Risk Evaluate) 
Source: http://www.heartscore.org/ru_RU  
Purpose: clinical tool for the assessment of the fatal CV event risk in the next 10 years.  The 
scale has been developed for the countries with high CV mortality rate (including Russia) based 
on the following factors: age, smoking, SBP  and total cholesterol levels.  Level od HDL-C is not 
taken into consideration in this scale. It is recommended to use SCORE scale to assess risk in 
asymptomatic patients older than 40 years, without CVD, diabetes mellitus, chronic kidney 
disease or familial hypercholesterolemia   
 

31 
 
 
 
 
 
Interpretation:  
Total CV risk according to SCORE scale:  
Less than 1% — low.  
1 - 4% —  moderate.  
5% - 9% — high. 
> 10% - very high 
 
 
Appendix 6. Categories of CV risk and target levels of LDL-C [15] 
 
Risk 
Definition 
Target level ofLDL-C, mmol/l 
(mg/dl) 
Extreme 
Combination of  ACVD1 with DM 2 and/or FH 
or two cardiovascular complications within 2 
year2  in a patient with ACVD regardless of 
optimal  hypolipidemic therapy and/or 
achieved level of LDL-C  ≤ 1,4 mmol/l 
< 1,4 (55), optimal < 1,0 (40) 
Very high 
 - Documented CVD with clinical or 
based on instrumental findings 
 (history of ACS, stable angina, PCI, 
CAPG or other interventions on the 
arteries, 
< 1,4 (55) or decrease from 
baseline  ≥ 50%  

Stroke/TIA, atherosclerosis of 
peripheric arteries) 
– Clinically significant athersclerothic 
plaque based on CAG/CT (stenosis ≥ 
50% in 2 coronary arteries) or duplex 
scan of carotid arteries  (stenisos > 
50%) 
– DM + target organs damage + ≥ 3 RF 
and early start of DM 1 with the 
duration  > 20 years 
– CKD with eGFR  < 30 ml/min/1,73 
m2 
– SCORE risk  ≥ 10% 
– FH + CVD or RF  
High 
Important RF Total cholesterol > 8 
mmol/l, and/or LDL-C 
> 4,9 mmol/l and/or BP ≥ 180/110 mm 
Hg 
– FH without RF 
– DM without target organ damage, 
DM ≥ 10 years or with the RF   
–Moderate CKD with eGFR 30–59 
ml/min/1,73 m2 
– SCORE risk 5–10% 
– Hemodynamically non-significant 
atherosclerosis of non-coronar y 
arteries (stenosis  25–49%) 
< 1,8 (70) or decrease from 
baseline и ≥ 50%  
Moderate 
Young patients (DM 1 –  younger than 
35years, DM 2 – younger than  50 
years) with the duration of DM < 10 
years without target organ damage and 
RF  
– SCORE risk  1–5% 
< 2,6 (100) 
Low 
SCORE risk < 1% 
< 3,0 (116) 
 
Notes: LDL-C – Low-density lipoprotein cholesterol; DM – diabetes mellitus; FH – familial 
hypercholesterolemia; ACVD –  atherosclerothic cardiovascular disease; CVD – cardiovascular 
diseases; ACS –  acute coronary syndrome; PCI – percutaneous coronary intervention; CAPG – 
coronary artery bypass grafting; TIA – transient ischaemic attack; АСБ – 
атеросклеротическая бляшка; CAG – coronary angiography; CT – computer tomography; RF 
– risk factor; eGFR – glomerular filtration rate; SCORE Systematic Coronary Risk Evaluation. 
1 CAD: angina  3-4 FC, non-stable angina, history of MI, ischaemi stroke, PCI, CAPG, 
angioplastics of carotid arteriesor low extremities arteries, carotid endarterectomy, ilio-femoral, 
femoral-popliteal bypass grafting. 2 Miocardial infarction, non-stable angina, intermittent 

33 
 
claudication, transient ischaemic attack/ischaemic stroke. 3 Administration of statins in max 
tolerated dosage in comination with ezetimibe. 
 
 
Appendix 7 Target office BP levels depenfing on age and concomitant diseases [15] 
 
 
Age 
Target  office SBP mm Hg 
Target office 
DBP mm Hg 
HTN 
+ DM 
+ CKD 
+ CAD 
+ Strokeа/TIA 
18 – 64 
years 
< 130 if 
tolerated but 
not <120  
< 130 if 
tolerated but 
not <120 
<140 to 130 if 
tolerated 
 
< 130 if 
tolerated but 
not <120 
< 130 if 
tolerated but 
not <120 
70-79 
65-79 
yearsa 
130-139 if 
tolerated 
130-139 if 
tolerated 
130-139 if 
tolerated 
130-139 if 
tolerated 
130-139 if 
tolerated 
70-79 
≥ 80 b 
130-139 if 
tolerated 
130-139 if 
tolerated 
130-139 if 
tolerated 
130-139 if 
tolerated 
130-139 if 
tolerated 
70-79 
 
a Refers to the patients with the history of stroke and not to the BP measure in acute stroke.  
b Target levels can be modified in elderly fragile patients. 
 
Appendix 8 Cardiovascular risk factors [14] 
Male sex 
 
Age  ≥55 years in men, ≥65 years in women   
 
 
Smoking (currently or in the past) 
 
Dyslipidemia  (any of the named below parameters)  
o Total cholesterol >4,9 mmol/l and/or   
o LDL-C >3,0 mmol/l and/or   
o HDL-C in men  — <1,0 mmol/l (40 mg/dl), in women — <1,2 mmol/l (46 mg/dl)  
o Triglycerides >1,7 ммоль/л  
 
 
 Fasting hyperglycemia  5,6–6,9 mmol/l (102–25 mg/dl) 
o Impaired glucose tolerance    
 
 
 Increased body mass index  (BMI 25-29,9 kg/m2) or obesity  (BMI ≥ 30 kg/m2)  
 
 
 Family history of CHD development at young age (< 55 years in men and <65 years in 
women)  
 

 
 Uric acid  (≥360 mcmol/l in women, ≥420 mcmol/l in men)  
 
 
 Development of HTN at young age in parents or in the family   
 
 
 Early menopause  
 
 
 Sedentary lifestyle 
 
 
 Psychological or social economic factors   
 
 
 Heart rate  ( >80 Beats per min at rest)  
 
 
 
 
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