title: An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.
abstract: BACKGROUND
  There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability.
  
  
  METHODS
  We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up.
  
  
  RESULTS
  At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment.
  
  
  CONCLUSIONS
  This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry ACTRN12607000099426.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodgers
authors.forename: Anushka
authors.initials: A
authors.lastname: Patel
authors.forename: Otavio
authors.initials: O
authors.lastname: Berwanger
authors.forename: Michiel
authors.initials: M
authors.lastname: Bots
authors.forename: Richard
authors.initials: R
authors.lastname: Grimm
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Rod
authors.initials: R
authors.lastname: Jackson
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
authors.forename: Jim
authors.initials: J
authors.lastname: Neaton
authors.forename: Neil
authors.initials: N
authors.lastname: Poulter
authors.forename: Natasha
authors.initials: N
authors.lastname: Rafter
authors.forename: P Krishnam
authors.initials: PK
authors.lastname: Raju
authors.forename: Srinath
authors.initials: S
authors.lastname: Reddy
authors.forename: Simon
authors.initials: S
authors.lastname: Thom
authors.forename: Stephen
authors.initials: S
authors.lastname: Vander Hoorn
authors.forename: Ruth
authors.initials: R
authors.lastname: Webster
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002784:Cholesterol / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012306:Risk; D055815:Young Adult
chemical_list: D002317:Cardiovascular Agents; D004338:Drug Combinations; D010919:Placebos; D002784:Cholesterol