title: The combined use of aspirin, a statin, and blood pressure-lowering agents (polypill components) and the risk of vascular morbidity and mortality in patients with coronary artery disease.
abstract: OBJECTIVE
  Patients with established coronary artery disease (CAD) are likely to receive a combination of aspirin, a statin, and blood pressure (BP)-lowering agents. Combining these pharmacologic agents into a cardiovascular combination pill, such as a polypill, could be considered to reduce prescription gaps and nonadherence in high-risk patients. We aimed to evaluate the effect of the concomitant use of aspirin, a statin, and BP-lowering agent(s) in patients with CAD on vascular morbidity and mortality in current clinical practice in an observational study to provide insights in the combination pill concept related to feasibility and applicability.
  
  
  METHODS
  In total, 2,706 patients with CAD enrolled in the Second Manifestations of ARTerial disease study were followed for the occurrence of a subsequent vascular event (ie, myocardial infarction, ischemic cerebrovascular accident, vascular death) and all-cause mortality. The relationship between combination therapy and cardiovascular events and all-cause mortality was assessed using Cox proportional hazards regression models to calculate hazards ratios (HRs) with a 95% CI. Both covariate and propensity score adjusting methods were used to reduce confounding by indication.
  
  
  RESULTS
  A combination of aspirin, a statin, and ≥1 BP-lowering agent(s) was used by 67% of the patients. During a median of 5.0 years (interquartile range 2.4-10.2 years), 347 vascular events occurred and 162 patients died. Combination therapy with aspirin, statin, and ≥1 BP-lowering agent was associated with a lower risk of myocardial infarction (HR 0.68, 95% CI 0.49-0.96), ischemic cerebrovascular accident (HR 0.37, 95% CI 0.16-0.84), composite vascular end point (HR 0.66, 95% CI 0.49-0.88), vascular mortality (HR 0.53, 95% CI 0.33-0.85), and all-cause mortality (HR 0.69, 95% CI 0.49-0.96) compared with the absence of combination therapy, after adjusting for confounding covariates in a propensity score. The use of 1 or only 2 components of combination therapy was associated with a higher risk for cardiovascular events compared with the combined use of aspirin, a statin, and ≥1 BP-lowering agent(s).
  
  
  CONCLUSIONS
  Two-thirds of the patients with CAD use a combination of aspirin, a statin, and ≥1 BP-lowering agent(s), components of a cardiovascular fixed-dose combination pill. Combination therapy with these agents is associated with a lower risk of vascular events and total mortality. Although treatment effect in observational studies should be interpreted with caution, the results of this study support supposed benefits from combination therapy. However, the effect of fixed-dose combination pill on clinical outcome needs to be demonstrated in randomized clinical trials.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Melvin
authors.initials: M
authors.lastname: Lafeber
authors.forename: Wilko
authors.initials: W
authors.lastname: Spiering
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: Hendrik
authors.initials: H
authors.lastname: Nathoe
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D001241:Aspirin