BACKGROUND AND PURPOSE:

• Yusuf et al. (NEJM, 2020) evaluated the efficacy and safety of the polypill alone (containing lipid-lowering and blood-pressure–lowering medications), aspirin alone, and the combination of polypill plus aspirin for the reduction of cardiovascular events among people at increased risk

METHODS:

• Double-blind, randomized, placebo-controlled trial
  • TIPS-3 (the International Polycap Study 3)
• Participants
  • Men ≥50 years of age or older | Women ≥55 years
  • No history of CVD
  • Elevated INTERHEART Risk Score indicating intermediate or high cardiovascular risk
• Interventions
  • Polypill: Simvastatin 40 mg | Atenolol 100 mg | Hydrochlorothiazide 25 mg | Ramipril 10 mg |
  • Aspirin: 75 mg
• Study design
  • Patients were assigned to intervention using a 2-by-2-by-2 factorial design
    • Polypill vs placebo
    • Aspirin vs placebo
    • Polypill + aspirin vs double placebo
• Primary outcome
  • For polypill alone and polypill + aspirin interventions
    • Composite of the following: Major cardiovascular events (including) death from cardiovascular causes, stroke, and myocardial infarction, plus heart failure, resuscitated cardiac arrest, and arterial revascularization
  • For aspirin alone
    • Death from cardiovascular causes | Myocardial infarction | Stroke

RESULTS:

• 5713 participants were randomized
  • Mean follow-up: 4.6 years
• LDL levels and systolic blood pressure were lower with the polypill and the combination therapy vs placebo
  • LDL cholesterol level: Lower by 19.0 mg per deciliter (0.50 mmol per liter)
  • Systolic blood pressure: Lower by 5.9 mm Hg
• There were no significant differences in the primary outcome for the following
  • Polypill vs placebo
    • Polypill: 4.4% incidence
    • Placebo: 5.5%
    • Hazard ratio (HR) 0.79 (95% CI, 0.63 to 1.00)
  • Aspirin vs placebo
    • Aspirin: 4.1%
    • Placebo: 4.7%
    • HR 0.86 (95% CI, 0.67 to 1.10)
• The primary outcome occurred in fewer patients in the combined treatment
  • Combined vs double placebo
    • Combined: 4.1%
    • Double-placebo: 5.8%
    • HR 0.69 (95% CI, 0.50 to 0.97)
• The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups

CONCLUSION:

• Use of combination therapy with polypill (statin plus three blood-pressure–lowering drugs) plus aspirin resulted in a 31% lower relative risk of cardiovascular events in a primary-prevention population at intermediate risk

Learn More – Primary Sources:

Polypill with or without Aspirin in Persons without Cardiovascular Disease

Related ObG Topics: