The Program to Assess the Influence of Routing and In-depth Consultation of Patients With Cardiovascular Risk Factors on the Choice of Medicine and Treatment Compliance
Conditions: Lipid Metabolism Disorders
Sponsor: The League of Clinical Research, Russia

 
1 
PROTOCOL SYNOPSIS 
of research project 
 “The program to assess the influence of routing and in-depth consultation of patients with 
cardiovascular risk factors on the choice of medicine and treatment compliance” 
 
Version 3, March 30, 2018 
 
 
Organized by: 
Russian Society for Prevention of Non-Infectious Diseases 
League of Clinical Research 
 
Study sponsor 
Pfizer Ltd. 
 
Project title 
 
The program to assess the influence of routing and in-depth 
consultation of patients with cardiovascular risk factors on the 
choice of medicine and treatment compliance. 
 
Short title of the project 
 
3P (Primary Prevention Program) 
 
Study type 
A pharmacoepidemiological study (evaluation of specifics of the 
use and the effects of drugs in a large patient number in the real 
world medical settings). 
 
Methodology of the study A systematic collection of retrospective and prospective data based 
on non-interventional patient observation, aimed to assess the risks, 
course and outcomes of a disease or a group of diseases: 
• the retrospective part: database of patients with 
cardiovascular risks; 
• the prospective part: observation of patients in the real world 
medical practice. 
 
The research program will have two parts: 
• The main part of the program (from the beginning of 
treatment to month 6): subjects with cardiovascular risk will 
be followed for 6 month after administration of treatments 
to reduce the risks. All study sites that have consented to 
participated in this research project, will take part in this 
study phase 
• A 6-month extension of the main program (from month 6 to 
month 12): subjects with the risk of cardiovascular disease 
will be followed for additional 6 months after the end of the 
main part of the program (from month 6 to month 12 after 
administration of treatments to reduce the risks).  All study 
sites that have consented to participated in the 6-month 
extension of the research project can take part in this 
extension. 
 
 
Background and 
rationale 
It is common that subjects with the risk of cardiovascular disease do 
not have proper preventive care. 
Cardiovascular disorders are known to be the leading cause of death 

 
2 
 
in Europe. About 4,3 million people die annually from these 
diseases. In November 2010, the results of a large European study 
were released that showed that an improvement of preventive care 
can substantially reduce cardiovascular mortality.  
The Epidemiological study of European Cardiovascular Risk 
patients: Disease prevention and management in usual daily 
practice aimed at evaluation of the influence of cardiovascular risk 
factors on mortality. In addition, the investigators assessed how 
successful was the management of these risk factors. The results 
obtained confirmed an increase of cardiovascular mortality in the 
presence of one or more risk factors (smoking, arterial 
hypertension, diabetes mellitus, increased cholesterol levels and 
obesity). It raises concern that in everyday clinical practice these 
factors are not adequately managed, that may be a cause of the rise 
in cardiovascular mortality.  
Hyperlipidemia is the second (after arterial hypertension) cause of 
early mortality in Russia. Hyperlipidemia can be associated with 
both increased low density lipoprotein cholesterol and triglyceride 
levels. Hypercholesterolemia is a confirmed risk factor of 
atherosclerotic cardiovascular disease and its complications. 
 
Objectives of the project 
 
1. To make physicians (internists, cardiologists, medical 
specialists working in preventive facilities) familiar with current 
approaches to assessment of cardiovascular risks and their 
management through timely administration of corresponding 
treatments, by organization of training activities (web 
conferences, meetings, round table discussions). 
2. To inform physicians, especially those in primary care, on the 
importance of a thorough assessment of cardiovascular risks and 
timely administration of therapy. 
3. To analyze databases currently effective in medical institutions 
(those on healthy subjects and patients) in order to identify 
subjects with cardiovascular risk factors. 
4. To assess blood lipids in subjects with suspected high 
cardiovascular risk. 
5. To perform in-depth medical consultations of subjects on the 
importance of primary cardiovascular prophylaxis, including by 
means of preventive statin treatment (with the information on 
original drugs and generics, social programs by manufacturers 
implemented in pharmacies).  
6. To assess efficacy of the combination of preventive activities 
(in-depth medical consultation of patients on their treatment; 
sms reminders on the necessity to comply with their doctor’s 
prescriptions) on patients’ compliance to treatment. 
7. To follow changes in cardiovascular risk factors with associated 
assessment of patients’ compliance to medical 
recommendations.  
 
Number of study sites 
6 (Kazan, Novosibirsk, Omsk, Samara, St. Petersburg, Ufa). 

 
3 
 
Patient number  
 
The target patient number is 12,000. 
Study period 
Development and approval of the project materials (protocol, 
electronic database): March 31, 2017. 
Start-up meeting: April 2017. 
Preparation, printing and delivery of the project materials: April 30, 
2017. 
First patient in: May 1, 2017. 
Last patient in: April 30, 2018. 
End of data collection for the main part of the program: October 30, 
2018. 
Analysis of the results and preparation of the final study report on 
the main part of the program: December 31, 2018. 
End of data collection for the 6-month extension phase: April 30, 
2019. 
Analysis of the results and preparation of the final study report: 
June 30, 2019.  
 
Study condition 
 
Cardiovascular risk factors. 
Special attention will be given to lipid level assessments. 
 
Study treatment 
 
Statins included into the list of life-saving and essential drugs and 
administered for correction of lipid spectrum to prevent 
cardiovascular disorders in the real world medical setting. 
 
Ethical and regulatory 
aspects 
 
The state registration of the project is planned to be done in the 
Federal State Research Institution “Center of Informational 
Technologies and Executive body systems” of the Ministry of 
Education and Science of the Russian Federation, in accordance 
with the Act of the Government of the Russian Federation №279 
from March 31, 2009. 
 
It is planned to establish a Research and Advisory Committee for 
the project.   
 
It is planned that the study materials will be approved by an 
Intercollegiate Ethics Committeeм. 
 
Personal data management in the project will be done in accordance 
with the Federal Law 152-FЗ from July 27, 2006 (version of June 4, 
2014). 
The Russian Society for Prevention of Non-Communicable 
Diseases and the League of Clinical Research will receive blinded 
data on the study subjects, i.e. the participating study sited will 
implement the blinding procedure on personal data (Art. 3, par.9, 
152-FЗ). 
 
To improve data quality, monitoring activities will be implemented 
in the main part of the program, in accordance with normative 
requirements on performance of research as follows: 
• The National Standard of the Russian Federation from 

 
4 
27.09.2005 GOST R 52379-2005 “Good Clinical Practice”, 
• The Decree of the Ministry of Health and Social 
Development of Russia №757n from 26.08.2010 г. “On 
approval of the Order of pharmacovigilance monitoring of 
safety of pharmaceuticals for medical use, registration of 
adverse effects, serious adverse reactions, unexpected 
adverse reactions during the use of pharmaceuticals for 
medical use”.  
 
 
 
 
Criteria and methodology 
of medical chart selection 
for further screening 
 
 
 
 
 
 
 
 
 
 
Inclusion criteria 
 
 
 
 
 
 
 
 
 
 
Exclusion criteria 
 
The monitoring will be performed by an independent third party (a 
contract research organization) and will include (but not limited to) 
visits of study monitors to study sites and check-ups of the study 
materials. 
 
• Total cholesterol >5 mmol/L 
• Additional risk factors identified during previous screening: 
• age 40-65 years 
• arterial hypertension (SBP>140 mmHg, DBP>90 
mmHg) or antihypertensive treatment 
• history of dyslipidemia  
• smoking 
• overweight or obesity (BMI ≥25,0) 
• diabetes mellitus 
• chronic renal disease. 
 
Data on the following subjects is planned to be collected in the 
project: 
• Aged from 40 to 65 years inclusively 
• With a high (≥5%) cardiovascular risk measured by SCORE1 
and low density lipoprotein (LDL) levels of ≥2,5 mmol/L, 
or 
with a very high (≥10%) cardiovascular risk measured by 
SCORE and LDL levels ≥1,8 mmol/L 
or 
With atherosclerotic stenosis of brachiocephalic arteries of 
>50% in the absence of cerebrovascular disease2 
• No contraindications to statin treatment and not taking stating at 
study entry. 
 
• History of the following clinically significant events and 
conditions: 
(а) myocardial infarction 
(б) stroke 
(в) transient ischemic attack 
• Presence of the following diseases at the time of a statin 
administration: 
 
1 SCORE: Systematic COronary Risk Evaluation. 
 
2 If atherosclerosis of brachiocephalic arteries has been confirmed either by data obtained from the source medical documentation or 
identified during the work-up within routing medical care of the medical institution; decision to perform such a work-up can be made by a 
doctor and is unrelated to performance of the given research project. 
 

 
5 
(а) ischemic heart disease 
(б) heart failure 
(в) peripheral artery atherosclerosis  
(г) atherosclerotic stenosis of brachiocephalic arteries with 
cerebrovascular disease3. 
 
Subjects must give their consent for processing of their personal 
data for the purposes of this scientific project. 
 
Data to be collected 
• Demographic characteristics 
(а) gender 
(b) age (full years by the time when written informed consent is 
signed) 
• cardiovascular risk factors: 
(а) hypercholesterolemia (based on the results of lipid tests, see 
below) 
(b) smoking status (yes/no) 
(c) blood pressure (systolic blood pressure, mmHg; diastolic blood 
pressure, mmHg) 
(d) diabetes mellitus (yes/no) 
(e) height (at Visit 1) and weight (at all visits) for calculation of body 
mass index (BMI) 
• blood lipids (all in mmol/L): 
(а) total cholesterol 
(b) low density lipoprotein cholesterol 
(c) high density lipoprotein cholesterol 
(d) triglycerides 
• treatment administered for prevention of cardiovascular disease: 
(а) statin prescribed for prevention of cardiovascular disease (name; 
original /generic; dose mg/daily) 
(b) other treatments prescribed for prevention of cardiovascular 
disease (name; original /generic) 
(c) if a drug is withdrawn, the reason for withdrawal: 
- by prescribing physician due to low efficacy; 
- by prescribing physician due to poor tolerance; 
- by another physician due to any reason; 
- unavailability of the drug; 
- patient’s decision; 
- other reasons 
(d) duration of statin therapy, months, 
(e) proportion of subjects who continue to take statin by the end of 
the main part of the program (6 mo) and by the end of the 6-mo 
extension of the main program (12 mo) 
(f) Morisky-Green test, scores (see Appendix 1). 
 
• development of one of the following conditions (disorders) during the 
trial: 
(а) myocardial infarction (yes; no) 
(b) stroke (yes; no) 
(c) transient ischemic attack (yes; no) 
 
3 If cerebrovascular disease is present, statin administration cannot be considered as primary prevention. 

 
6 
(d) ischemic heart disease (yes; no) 
(e) heart failure (yes; no) 
(f) atherosclerosis of brachiocephalic arteries (yes; no) 
(g) hospitalization (yes; no; if yes, due to a cardiovascular disease or 
due to another reason) 
(h) emergency call (yes; no; if yes, due to a cardiovascular disease or 
due to another reason)  
(i) revascularization (yes; no) 
(j) death (if yes, due to a cardiovascular disease or due to another 
reason). 
 
Time points of 
assessments 
 
In this study data obtained in the real world medical practice will be analyzed. 
It is assumed that subjects will be assessed and treated according to the usual 
practice of their medical centers and at a physician’s discretion.  
It is desirable that the standard medical practice of the participating study sites 
involves regular assessment of patients who have been administered statins for 
improvement of their lipid spectrum to prevent cardiovascular diseases. It is 
assumed that patients to whom a statin has been prescribed for prevention of 
cardiovascular diseases should be assessed approximately at 1 to 2, 3 to 4, 5 to 
6, and 11 to 12 months to monitor their treatment compliance, potential 
treatment modifications, course of their cardiovascular risks or cardiovascular 
disorders.  
 
Since this research project is aimed to assess the examination and treatment of 
patients in the real world medical practice, the study organizers will not set 
any concrete time points at which patients should make their visit to the 
doctor. The type of the follow-up should correspond to that adopted in the 
medical institution.  
 
At the same time, it is desirable that during the main part of the program those 
subjects that have been prescribed a statin, would see their doctors three time, 
approximately at 1 to 2, 3 to 4, and 5 to 6 mother after initiation of statin 
treatment. Those participating in a 6-month extension of the main part of the 
program are recommended to be assessed at 11 to 12 months after initiation of 
statin treatment.  
 
 
Data management 
and analysis 
 
Remote input of data (data into the electronic database will be entered by the 
participating physicians from the workplace). Data will be entered in 
depersonalized form. 
The methods of descriptive statistics will be used for the whole population for 
all the indicators studied. 
 
For those categories for which it is possible (for example, "high-density 
lipoprotein cholesterol"), the data will be reduced to time points "after 2 
months"; "in 3 months"; "in 6 months"; "in 12 months", using the method 
move forward the last observation data (Last Observation Carried Forward, 
LOCF). 
 
In addition, using descriptive statistics methods, all the studied indicators will 
be analyzed separately for the following populations: 
• 
population in which a set of preventive measures was carried out (in-

 
7 
depth medical advice to patients about taking therapy, sms reminders about the 
need to follow the doctor's prescription) 
• 
population in which a set of preventive measures was not carried out. 
 
Using the methods of comparative statistics, the following variables will be 
compared: 
• 
Change in the lipid spectrum of the blood during the study period: 
(A) in the whole population 
(B) in a population in which a set of preventive measures was carried out (in-
depth medical advice to patients about taking therapy, sms-reminders about the 
need to follow the doctor's prescription) 
(C) in a population in which a set of preventive measures was not carried out. 
 
In addition, using the methods of comparative statistics, the following 
indicators will be compared: 
• 
reasons for withdrawal of therapy 
• 
duration of statin therapy: between groups; for each trade name 
• 
Percentage of patients who continued to receive statins at the end of the 
main part of the program (6 months): between groups; for each trade name 
• 
Percentage of people who continued to receive statins at the end of the 
6-month continuation of the main part of the program (12 months): between 
groups; for each trade name 
• 
results of Moriski-Green test 
• 
blood pressure 
• 
smoking status 
• 
change in body mass index 
• 
development of one of the following conditions (occurrence of the 
following diseases, development of the following events) during the study 
period: 
(A) myocardial infarction 
(B) stroke 
(C) transient ischemic attack 
(D) ischemic heart disease 
(E) heart failure 
(E) atherosclerosis of brachiocephalic arteries 
(G) atherosclerotic disease of peripheral arteries 
(H) hospitalization 
(I) call an ambulance 
(K) revascularization 
(K) death, 
 
in a population in which a set of preventive measures was carried out (in-depth 
medical advice to patients about the admission of therapy, sms-reminders 
about the need to follow the doctor's prescription), and in a population in 
which a set of preventive measures was not carried out. 
 
At the end of the study, a final report will be prepared in Russian. 
 
General description 
of the study 
 
 
6 centers of medical prevention (MSC), located in different regions of Russian 
Federation will take part in this project, in cooperation with other medical and 
preventive institutions. 
 

 
8 
 
During the first phase of the project (screening 1) is expected to be screened in 
the existing health care institutions of primary health care databases (patients, 
healthy individuals) and identify individuals; 
(a) not currently suffering from cardiovascular disease (diseases), which are 
exclusion criteria for this scientific program, 
(b) do not have the history of conditions (diseases), which are exclusion 
criteria in this scientific program, 
(c) not receiving statin for the prevention of cardiovascular disease, 
(d) having risk factors for cardiovascular disease. 
 
Sufficient number of subjects should be screened in each center to include 
2,000 patients who meet the inclusion and exclusion criteria in the project. 
 
During the second phase of the project (screening 2) subjects will be invited to 
the study centre in medical prevention and treatment-and-prophylactic 
institutions (MPI), or to physician to confirm that subject: 
(a) does not currently suffer from cardiovascular disease (diseases), which are 
exclusion criteria for this scientific program, 
(b) does not have a history of conditions (diseases), which are exclusion 
criteria for this scientific program, 
(c) does not receive statins for the prevention of cardiovascular diseases, 
(d) has risk factors for cardiovascular disease, 
(e) has reasonable indications for determining the lipid spectrum. 
 
During the third phase of the project (screening 3) subjects who were selected 
during the second phase, will be determined lipid profile by express test. 
Persons with lipid metabolism disorders, which are indications for prescribing 
vital and essential statins for the prevention of cardiovascular diseases, are 
prescribed statins in accordance with standard practice of medical institution. 
 
Following the appointment of statin subject signs an informed consent for 
processing of personal data. From this moment, the subject is considered 
included in the scientific research. 
 
It is necessary to include 2,000 patients in each center that meet the inclusion 
and exclusion criteria. 
 
During the fourth phase (the main part of the program - observation): 
(a) all subjects will be consulted about the prevention of cardiovascular 
diseases and the use of medicines for this purpose 
(b) subjects will be randomized (using the CRStat system) in two groups in a 
ratio 1: 1; in one of the groups will be carried out a profound consultation 
(different from standard practice for this medical institution) on the importance 
of primary prevention of cardiovascular diseases, including preventive 
reception of statins 
(c) subjects in profound consultation group will receive regular reminders (2 
times a month) via SMS and calls to check maintenance the doctor's 
recommendations and follow-up visit to study centre 
(d) subjects will come for final examinations (consultations) to study doctor. 
 
During the fifth phase (6-month continuation of the program - observation): 
(a) subjects in profound consultation group will receive regular reminders (2 

 
9 
times a month) via SMS and calls to check maintenance the doctor's 
recommendations and follow-up visit to study centre 
(b) subjects will come for the final examination (consultation) to study doctor. 
 
It is desirable that medical prevention and treatment-and-prophylactic 
institutions (MPI) take part in the program, in witch standard medical practice 
involves periodic surveys of persons receiving statins for lipid correction and 
for prevention of cardiovascular disease: approximately in 1-2, 3-4, 5-6 and 11 
-12 months after beginning of statin therapy. 
 
Potential medical, 
social and economic 
consequences of the 
project 
 
 
The results of the project (medical statistical and pharmaco-epidemiological) 
will be presented to the Russian medical community and healthcare 
institutions in order to: 
(a) draw attention to the problem of primary prevention of cardiovascular 
diseases, 
(b) based on the analysis of the results of the study help healthcare 
professionals and healthcare providers to choose the right line for treatment 
people with high cardiovascular risks, including timely administration of 
statins, 
(c) demonstrate the advantages of complex preventive measures (profound 
consultation about necessity of maintenance the doctor's recommendations; 
sms reminders about the need to follow the doctor's prescription), 
 
having the aim of reducing the number of cardiovascular diseases in Russian 
Federation. 
 
In order to promote the development of modern approaches to the prevention 
of cardiovascular diseases, to demonstrate to a wide range of doctors the 
benefits of timely prescription of statins for primary prevention of 
cardiovascular diseases, during the project it is planned to hold meetings, 
conferences, roundtables on the prevention of cardiovascular diseases with the 
aim of discussing the progress of scientific research in Russia and abroad, as 
well as the participation of physicians in the work of international congresses 
and conferences with the purpose of increasing their own knowledge and 
further transfer of this knowledge to Russian specialists. 
 
 

 
10 
 
References 
 
Boytsov S.А. Epidemiological study of European Cardiovascular Risk patients: Disease prevention 
and management in usual daily practice [EURIKA]). 
http://www.scardio.ru/content/images/documents/epidemiologicheskoe_issledovanie_sredi_pacientov_
s_riskom_serdechno.doc 
 
Ershova A.I., et al. Diagnosis and treatment of patients with advanced hypercholesterolemia in the real 
out-patient practice (the data of REKVAZA Registry). Rational Pharmacotherapy in Cardiology. 2014; 
10 (6). p. 612-616. 
 
Lukina Yu.V., Martsevich S. Yu., Kutishenko N.P. The Moriski Green Scale: the pluses and minuses 
of the generic test and error analysis. Rational Pharmacotherapy in Cardiology, 2016; 12 (1). p. 63-65.