title: Cardiovascular disease prevention using fixed dose pharmacotherapy in Iran: updated meta-analyses and mortality estimation.
abstract: BACKGROUND
  Short term randomized trials have shown the effectiveness of a fixed dose combination therapy (known as Polypill) on reducing blood pressure and serum cholesterol but the impact of Polypill on cardiovascular disease risk or mortality has not yet been directly investigated. Previous studies combined the effects of each component assuming a multiplicative joint risk model that may have led to overestimating the combined effects. We conducted an updated meta-analysis of randomized trials of anti-hypertensives, and aspirin. We used the estimated effect sizes applying a more conservative assumption to estimate the number of ischemic heart disease (IHD) and stroke deaths that could have been averted by Polypill in Iranians aged 55 years or older in 2006.
  
  
  METHODS
  We searched Medline and reviewed previous meta-analyses to select randomized trials on Angiotensin Converting Enzyme-inhibitors, thiazides, aspirin, and statins. We used a random-effects model to pool relative risks for each component and estimated the joint relative risks using multiplicative and additive assumptions for 4 combinations of Polypill components. We used age- and cause-specific mortality, separately by gender, and estimated the number of preventable deaths from IHD and stroke.
  
  
  RESULTS
  Under the additive joint RR assumption, the standard Polypill formulation was estimated to prevent 28500 (95% CI: 21700, 34100) IHD deaths and 12700 (95% CI: 8800, 15900) stroke deaths. Removing aspirin from the combination decreased preventable IHD deaths by 15% under the additive assumption (5600 deaths) and by 21% under the multiplicative assumption (6800 deaths) and reduced preventable stroke deaths under both additive and multiplicative assumptions by 3% (300 deaths). There was no significant difference between Polypill combinations with anti-hypertensive agents in full-dose or half-dose.
  
  
  CONCLUSIONS
  Polypill can prevent a large number of IHD and stroke deaths in Iran. The cost-effectiveness, feasibility, and acceptability of this prevention strategy remain to be investigated.
authors.affiliation: Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. sadaf.g.sepanlou@gmail.com
authors.forename: Sadaf G
authors.initials: SG
authors.lastname: Sepanlou
authors.forename: Farshad
authors.initials: F
authors.lastname: Farzadfar
authors.forename: Elham
authors.initials: E
authors.lastname: Jafari
authors.forename: Goodarz
authors.initials: G
authors.lastname: Danaei
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007492:Iran; D008875:Middle Aged; D015233:Models, Statistical; D017202:Myocardial Ischemia / Q000401:mortality / Q000517:prevention & control*; D012306:Risk; D020521:Stroke / Q000401:mortality / Q000517:prevention & control*; D049971:Thiazides / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D049971:Thiazides; D001241:Aspirin