Cardiovascular Disease
Conditions
Brief summary
The purpose of this pilot study is to provide data on the feasibility of conducting a large clinical trial on the polypill (combination of aspirin, angiotensin converting enzyme inhibitor, thiazide diuretic, and statin) for primary prevention of cardiovascular disease (CVD). We hypothesized that A polypill comprising the aforementioned four components would significantly reduce the estimated 10-year total CVD risk score with high adherence and no significant increase in adverse effects compared to the standard practice.
Detailed description
This is an open-label, parallel-group, randomized clinical trial comparing a Polypill to Standard Practice (defined as usual care administered to patients with similar conditions). Approximately 200 participants will be recruited from three sites in Sri Lanka: The National Hospital of Sri Lanka, Colombo; Teaching Hospital, Kegalle, and Teaching Hospital, Kandy. Subsequent to granting written informed consent, patients will undergo screening and baseline evaluation to confirm eligibility, followed by randomization to the Polypill or to the Standard Practice study arm. Patients receiving either intervention will return for a total of three monthly clinic visits. Physician acceptability will be evaluated through a five-question survey will be mailed to a random sample of physicians from the participating clinical sites and to the Council of General Practitioners in Sri Lanka. Patient acceptability will be measured in participants who will complete the study as well as those who will be screened but not eligible
Interventions
DRUGRed Heart Pill 2b (Polypill)
Arm A will receive the polypill (Red Heart pill 2b) which is a combination of aspirin (75 mg), simvastatin (20g), lisinopril (10mg) and hydrochlorothiazide (12.5 mg)
OTHERStandard Practice
Arm B will receive management of their CVD risk according to the usual care given to participants in similar conditions
Sponsors
World Health Organization
National Hospital of Sri Lanka
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Estimated 10-year total CVD risk score \> 20%. The total CVD risk assessment will be based on the recently developed WHO CVD risk prediction charts * No contraindication for treatment with aspirin, angiotensin converting enzyme inhibitors, low-dose diuretics, or statins * Informed consent given
Exclusion criteria
* Patients with established angina pectoris, coronary heart disease, myocardial infarction, transient ischemic attacks, stroke, peripheral vascular disease, coronary revascularization and/or carotid endarterectomy Left ventricular hypertrophy (on ECG) or hypertensive retinopathy (grade III or IV) * Patients with secondary hypertension * Patients with diabetes type 1 or 2 with overt neuropathy or other significant renal disease. * Known renal failure or impairment * Atrial fibrillation * ALT \> 1.5 times the upper limit of normal * History of liver cirrhosis or hepatitis * History of recent gastrointestinal bleeding (within the last year) * Women in child bearing period * History of life-limiting diseases or events * Unwillingness to sign informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of the Estimated 10-year Total Cardiovascular Risk Score | Six months | Estimated 10-year CVD total risk score were calculated in the field centers and in the Coordinating Center from the measures of blood pressure and total cholesterol and from the medical history data collected during each visit using the WHO CVD prediction chart. The estimated 10-year CVD total risk calculated by the Coordinating Center were used for analysis. the score is based on systolic blood pressure and total cholesterol measures as well as on medical history data (monthly). Each one of these risk factors is assigned a point in the score and then linked to a table that mention the calculated CVD risk |
Countries
Sri Lanka
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| The Polypill Group (Arm A) The Polypill Group (Arm A) received a Polypill composed of 75 mg aspirin, 20 mg simvastatin, 10 mg lisinopril and 12.5 mg hydrochlorothiazide
Red Heart Pill 2b (Polypill): Arm A will receive the polypill (Red Heart pill 2b) which is a combination of aspirin (75 mg), simvastatin (20g), lisinopril (10mg) and hydrochlorothiazide (12.5 mg) | 111 |
| Standard Practice Group (Arm B) Standard Practice
Standard Practice: Arm B received management of their CVD risk according to the usual care given to participants in similar conditions | 105 |
| Total | 216 |
Baseline characteristics
| Characteristic | The Polypill Group (Arm A) | Standard Practice Group (Arm B) | Total |
|---|---|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 7.4 | 59.0 years STANDARD_DEVIATION 6.9 | 59.1 years STANDARD_DEVIATION 7.2 |
| Sex: Female, Male Female | 77 Participants | 80 Participants | 157 Participants |
| Sex: Female, Male Male | 34 Participants | 25 Participants | 59 Participants |
| Systolic Blood Pressure | 164.7 mmHG STANDARD_DEVIATION 17.3 | 165.7 mmHG STANDARD_DEVIATION 19.2 | 165.2 mmHG STANDARD_DEVIATION 18.2 |
| Total Cholesterol | 5.7 mmol/L STANDARD_DEVIATION 1.3 | 6.1 mmol/L STANDARD_DEVIATION 1.3 | 5.9 mmol/L STANDARD_DEVIATION 1.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 99 | 12 / 104 |
| serious Total, serious adverse events | 26 / 99 | 29 / 104 |
Outcome results
Primary
Reduction of the Estimated 10-year Total Cardiovascular Risk Score
Estimated 10-year CVD total risk score were calculated in the field centers and in the Coordinating Center from the measures of blood pressure and total cholesterol and from the medical history data collected during each visit using the WHO CVD prediction chart. The estimated 10-year CVD total risk calculated by the Coordinating Center were used for analysis. the score is based on systolic blood pressure and total cholesterol measures as well as on medical history data (monthly). Each one of these risk factors is assigned a point in the score and then linked to a table that mention the calculated CVD risk
Time frame: Six months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| The Polypill Group (Arm A) | Reduction of the Estimated 10-year Total Cardiovascular Risk Score | 11.5 percent | Standard Deviation 113 |
| Standard Practice Group (Arm B) | Reduction of the Estimated 10-year Total Cardiovascular Risk Score | 11.1 percent | Standard Deviation 10 |