Phase II Study of Heart Polypill Safety and Efficacy in Primary Prevention of Cardiovascular Disease
Condition: Cardiovascular Disease; Hypertension; Hyperlipidemia; Heart Disease
MeSH terms: Cardiovascular Diseases; Heart Diseases; Hyperlipidemias
Intervention: Polypill; Placebo drug
Intervention description: Fixed dose combination therapy - aspirin 81mg, hydrochlorothiazide 12.5mg, enalapril 2.5mg and atorvastatin 20mg Once daily; Inactive tablet Once a day Identical in appearance to intervention drug
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 475.0
Sex: All
Minimum age: 50 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Cardiovascular disease; primary prevention; Polypill; efficacy; safety; ADR; Diabetes; Adherence; Compliance

Summary:

      Cardiovascular is a major cause of mortality in Iran, accounting for 45.7% of deaths. In
      Golestan (North Eastern Iran) preliminary findings from follow-up of the Golestan Cohort are
      consistent with national figures: with 45% (at least 22 of 48 deaths) of all deaths
      attributed to cardiovascular events. Cardiovascular diseases will become an increasing
      problem as the Iranian population ages.

      In 2003 Law and Wald proposed prevention of cardiovascular disease using fixed-dose
      combination therapy combining antihypertensive, lipid lowering and antiplatelet drugs in a
      single preparation. They proposed that this treatment should be offered to all persons at
      high risk of cardiovascular disease whether or not they have elevated blood pressure or
      elevated serum lipid concentrations.

      This pilot study aims to investigate the safety and efficacy of fixed-dose combination
      therapy with two antihypertensive drugs, aspirin and atorvastatin in a population who would
      not currently be considered eligible for antihypertensive treatment or for lipid lowering
      treatment.

      Methods:

      This is a double-blind randomized controlled trial. The intervention group will be assigned
      to take a tablet consisting of a single daily tablet comprising Aspirin 81mg,
      Hydrochlorothiazide 12.5mg, Enalapril 2.5mg and Atorvastatin 20mg. The control group will be
      assigned to an identical placebo.

      The population studied includes men aged 50 to 80 (inclusive) and women aged 55 to 80
      (inclusive) who are currently not eligible for or taking antihypertensive or lipid lowering
      therapy. Persons who are found at baseline to have blood pressure >160/100 mm Hg, total
      cholesterol >240mg/dL, existing cardiovascular disease or to be taking antihypertensive ore
      lipid lowering therapy are excluded.

      It is intended to randomize and follow up 500 subjects for 12 months. The primary outcome for
      the purpose of sample size calculation is change in systolic blood pressure. Additional
      outcomes include change in diastolic blood pressure, change in LDL cholesterol and occurrence
      of adverse events.
    

Eligibility criteria:

        Inclusion criteria

        All men over 50 to 80 and all women 55 to 80 who are resident in Kalaleh, Golestan, for at
        least one year.

        Exclusion criteria

          -  Existing cardiovascular disease (stroke, transient ischaemic attack, myocardial
             infarction or angina)

          -  Already taking antihypertensive drugs, aspirin or statins

          -  Already have clinical indications for treatment with antihypertensive drugs, aspirin
             or statins.

               -  Blood pressure >160/100 mm Hg

               -  Total Cholesterol > 240 mg/dL (or LDL >190 mg/dL)

          -  Probable diabetes: HbA1c >6.0

        Contraindication to a component of the Polypill

        Contraindications to aspirin

          -  Previous history of allergy to aspirin

          -  History of peptic ulcer bleeding in whole life or endoscopic evidence of peptic ulcer
             within the past 3 months

        Contraindications to statins

          -  Liver failure Contraindications to further blood pressure lowering

          -  Systolic blood pressure ≤90 mm Hg or diastolic blood pressure ≤70 mm Hg

          -  Symptomatic postural hypotension

          -  Difference between mean seated BP and standing BP greater than 20 mm Hg

        Contraindications to thiazide

          -  Uric acid >8 for men and uric acid >6 for women / gout (~10%)

          -  Creatinine >1.2 mg/dl

        Other predominant medical problem that may limit compliance with study treatment including:

          -  History of alcohol abuse: more than 60cc for women and more than 80cc for men

          -  History of drug abuse: IV drug abuser or eating or smoking more than 4 times a week

          -  Limiting psychiatric illness (eg: mania, schizophrenia, severe depression, psychosis
             or dementia)

          -  Limiting physical disability sufficient to prevent subject from walking

          -  Other life-threatening condition such as cancer