Coronary Heart Disease, Hypercholesterolemia
Conditions
Brief summary
This study is being performed to evaluate what variants of lipid-lowering therapy are used in Russian clinical practice in coronary heart disease (CHD) patients with hypercholesterolemia in whom the initial statin therapy did not achieve low density lipoprotein-cholesterol (LDL-C) goals. Additionally, the efficacy and safety of all variants of modified lipid-lowering therapy are to be evaluated.
Detailed description
Given the observational nature of this study and that the assessment of a specific hypothesis is not foreseen, statistical assumption is not planned and the sample size calculation was not performed. Taking into consideration the available data on the established safety profile of the therapy with statins and combination of ezetimibe with statins it has been suggested that a sample size of 750 patients will be sufficient to identify adverse events profile. The treatment effects will be characterized by descriptive and frequency parameters.
Interventions
DRUGEzetimibe
Dosage determined by the investigator based on standard and applicable routine clinical practice for CHD and hypercholesterolemia patients
DRUGStatin
Statin titration for the Statin Dose Titration group, and new statin treatment and dosage for the New Statin group, determined by the investigator based on standard and applicable routine clinical practice for CHD and hypercholesterolemia patients
Sponsors
Organon and Co
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male and Female, from 18 to 75 years old; * Established diagnosis of CHD; * Previous (at least, within 1 month before inclusion in the present study) treatment with statin; * Levels of plasma TC and LDL-C above the recommended target values (TC\> 4.5 mmol\\L; LDL-C\> 2.5 mmol/L); * The written informed consent signed prior to the start of participation in the study.
Exclusion criteria
* Contraindications for statin and ezetimibe (Ezetrol) administration in accordance with local Russian Federation medical instructions. * Patients refused to participate in the study and/or did not sign informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Receiving Each Variant of Modified Lipid-lowering Therapy: Statin Dose Titration, Administration of a New Statin, Administration of a Ezetimibe in Addition to a Current Statin. | During the study | Statins included: 1. statin dose (atorvastatin, fluvastatin, rosuvastatin, simvastatin) titration . 2. shift to a (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastin, simvastatin) different statin . 3. Ezetimibe added to existing statin (atorvastatin, lovastatin, rosuvastatin, simvastatin). |
| Percentage of Patients Per Group Who Reach Goal for Total Cholesterol (TC) (< 4.5 mmol/L) According to All-Russian Scientific Cardiologists Society (ARSCS) Recommendations by End of Observation | Visit 2 (Month 2, end of observation) | Statins included in this outcome measure included: 1. statin dose (atorvastatin, fluvastatin, rosuvastatin, simvastatin) titration. 2. shift to a different (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastin, simvastatin) statin . 3. Ezetimibe added to existing statin (atorvastatin, lovastatin, rosuvastatin, simvastatin). |
| Percentage of Patients Per Group Who Reached Goal for Low Density Lipoprotein (LDL-C) (< 2.6 mmol/L) According to ARSCS Recommendations by End of Observation | Visit 2 (Month 2, end of observation) | — |
| Percentage of Relative Change of Total Cholesterol (TC) Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups | Visit 2 (Month 2, end of observation) and Visit 1 (Day 0, baseline) | — |
| Percentage of Relative Change of LDL-C Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups | Visit 2 (Month 2, end of observation) and Visit 1 (Day 0, baseline) | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Patients Patients with established diagnosis of CHD and hypercholesterolemia who did not achieve the target values for TC and LDL-C with existing statin therapy and who consented to enroll in this observational study, allowing collection of data regarding change in treatment, and treatment efficacy and safety. | 712 |
| Total | 712 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Protocol Violation | 154 |
Baseline characteristics
| Characteristic | Enrolled Patients |
|---|---|
| Age, Continuous | 59.57 years STANDARD_DEVIATION 9.367 |
| Region of Enrollment Russian Federation | 712 participants |
| Sex/Gender, Customized Female | 324 participants |
| Sex/Gender, Customized Male | 386 participants |
| Sex/Gender, Customized Not Reported | 2 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 712 |
| serious Total, serious adverse events | 3 / 712 |
Outcome results
Primary
Percentage of Patients Per Group Who Reached Goal for Low Density Lipoprotein (LDL-C) (< 2.6 mmol/L) According to ARSCS Recommendations by End of Observation
Time frame: Visit 2 (Month 2, end of observation)
Population: The efficacy analysis set (n=557) included all enrolled subjects, by treatment (after treatment modification), who received at least one dose of the modified lipid-lowering treatment and for whom no protocol deviations were recorded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants Analyzed | Percentage of Patients Per Group Who Reached Goal for Low Density Lipoprotein (LDL-C) (< 2.6 mmol/L) According to ARSCS Recommendations by End of Observation | 42.3 Percentage of patients |
| Statin Dose Titration | Percentage of Patients Per Group Who Reached Goal for Low Density Lipoprotein (LDL-C) (< 2.6 mmol/L) According to ARSCS Recommendations by End of Observation | 26.3 Percentage of patients |
| New Statin | Percentage of Patients Per Group Who Reached Goal for Low Density Lipoprotein (LDL-C) (< 2.6 mmol/L) According to ARSCS Recommendations by End of Observation | 33.9 Percentage of patients |
Comparison: Significance of paired changes in the number of patients who achieved LDL-C target levels on Visit 2, for each treatment group comparisonp-value: <0.001McNemar
Primary
Percentage of Patients Per Group Who Reach Goal for Total Cholesterol (TC) (< 4.5 mmol/L) According to All-Russian Scientific Cardiologists Society (ARSCS) Recommendations by End of Observation
Statins included in this outcome measure included: 1. statin dose (atorvastatin, fluvastatin, rosuvastatin, simvastatin) titration. 2. shift to a different (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastin, simvastatin) statin . 3. Ezetimibe added to existing statin (atorvastatin, lovastatin, rosuvastatin, simvastatin).
Time frame: Visit 2 (Month 2, end of observation)
Population: The efficacy analysis set (n=557) included all enrolled subjects, by treatment (after treatment modification), who received at least one dose of the modified lipid-lowering treatment and for whom no protocol deviations were recorded. One subject each from the Ezetimibe and New Statin groups were excluded from this analysis due to missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants Analyzed | Percentage of Patients Per Group Who Reach Goal for Total Cholesterol (TC) (< 4.5 mmol/L) According to All-Russian Scientific Cardiologists Society (ARSCS) Recommendations by End of Observation | 50.4 Percentage of patients |
| Statin Dose Titration | Percentage of Patients Per Group Who Reach Goal for Total Cholesterol (TC) (< 4.5 mmol/L) According to All-Russian Scientific Cardiologists Society (ARSCS) Recommendations by End of Observation | 33.5 Percentage of patients |
| New Statin | Percentage of Patients Per Group Who Reach Goal for Total Cholesterol (TC) (< 4.5 mmol/L) According to All-Russian Scientific Cardiologists Society (ARSCS) Recommendations by End of Observation | 37.4 Percentage of patients |
Comparison: Significance of the differences in the number of patients per group who achieved goal TC levels on Visit 2.p-value: 0.007Pearson Chi-Square
Primary
Percentage of Patients Receiving Each Variant of Modified Lipid-lowering Therapy: Statin Dose Titration, Administration of a New Statin, Administration of a Ezetimibe in Addition to a Current Statin.
Statins included: 1. statin dose (atorvastatin, fluvastatin, rosuvastatin, simvastatin) titration . 2. shift to a (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastin, simvastatin) different statin . 3. Ezetimibe added to existing statin (atorvastatin, lovastatin, rosuvastatin, simvastatin).
Time frame: During the study
Population: The efficacy analysis set (n=557) included all enrolled subjects, by treatment (after treatment modification), who received at least one dose of the modified lipid-lowering treatment and for whom no protocol violations were recorded. One subject each from ezetimibe added to existing statin and new statin group were excluded (missing data)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants Analyzed | Percentage of Patients Receiving Each Variant of Modified Lipid-lowering Therapy: Statin Dose Titration, Administration of a New Statin, Administration of a Ezetimibe in Addition to a Current Statin. | Statin dose titration | 32.1 Percentage of patients |
| All Participants Analyzed | Percentage of Patients Receiving Each Variant of Modified Lipid-lowering Therapy: Statin Dose Titration, Administration of a New Statin, Administration of a Ezetimibe in Addition to a Current Statin. | New statin administered | 42.4 Percentage of patients |
| All Participants Analyzed | Percentage of Patients Receiving Each Variant of Modified Lipid-lowering Therapy: Statin Dose Titration, Administration of a New Statin, Administration of a Ezetimibe in Addition to a Current Statin. | Ezetimibe added on to existing statin | 25.5 Percentage of patients |
Primary
Percentage of Relative Change of LDL-C Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups
Time frame: Visit 2 (Month 2, end of observation) and Visit 1 (Day 0, baseline)
Population: The efficacy analysis set (n=557) included all enrolled subjects, by treatment (after treatment modification), who received at least one dose of the modified lipid-lowering treatment and for whom no protocol deviations were recorded. One subject each from the Ezetimibe and New Statin groups were excluded from this analysis due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants Analyzed | Percentage of Relative Change of LDL-C Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups | 32.06 mmol/L | Standard Deviation 15.59 |
| Statin Dose Titration | Percentage of Relative Change of LDL-C Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups | 26.81 mmol/L | Standard Deviation 19.852 |
| New Statin | Percentage of Relative Change of LDL-C Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups | 28.24 mmol/L | Standard Deviation 20.787 |
Comparison: Descriptive statistics of relative (%) change in LDL-C levels by the end of the study (Visit 2) compared to Baseline (Visit 1)
Comparison: Descriptive statistics of relative (%) change in LDL-C levels by the end of the study (Visit 2) compared to Baseline (Visit 1)
Comparison: Descriptive statistics of relative (%) change in LDL-C levels by the end of the study (Visit 2) compared to Baseline (Visit 1)
Comparison: Statin Dose Titration compared to New Statinp-value: 0.75695% CI: [-6.1604, 3.2977]Games-Howell
Comparison: Statin Dose Titration compared to Ezetimibep-value: 0.02395% CI: [-9.9072, -0.591]Games-Howell
Comparison: New Statin compared to Ezetimibep-value: 0.10795% CI: [-8.2523, 0.6169]Games-Howell
Primary
Percentage of Relative Change of Total Cholesterol (TC) Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups
Time frame: Visit 2 (Month 2, end of observation) and Visit 1 (Day 0, baseline)
Population: The efficacy analysis set (n=557) included all enrolled subjects, by treatment (after treatment modification), who received at least one dose of the modified lipid-lowering treatment and for whom no protocol deviations were recorded. One subject each from the Ezetimibe and New Statin groups were excluded from this analysis due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants Analyzed | Percentage of Relative Change of Total Cholesterol (TC) Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups | 25.76 mmol/L | Standard Deviation 12.306 |
| Statin Dose Titration | Percentage of Relative Change of Total Cholesterol (TC) Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups | 20.01 mmol/L | Standard Deviation 15.662 |
| New Statin | Percentage of Relative Change of Total Cholesterol (TC) Level Measured on Visit 2 Compared With the Baseline (Visit 1) in Each of the Three Therapy Groups | 22.82 mmol/L | Standard Deviation 14.035 |
Comparison: Descriptive statistics of relative (%) change in TC levels from Baseline at Visit 2
Comparison: Descriptive statistics of relative (%) change in TC from baseline at Visit 2
Comparison: Descriptive statistics of relative (%) change in TC from baseline at Visit 2
Comparison: Statin Dose Titration compared to New Statinp-value: 0.14395% CI: [-6.307, 0.6884]Games-Howell
Comparison: Statin Dose Titration compared to Ezetimbep-value: 0.00195% CI: [-9.4298, -2.0664]Games-Howell
Comparison: New Statin compared to Ezetimibep-value: 0.08695% CI: [-6.1948, 0.3171]Games-Howell