title: Assessment of the Cardiovascular Risk of Olmesartan Medoxomil-Based Treatment: Meta-Analysis of Individual Patient Data.
abstract: BACKGROUND
  Results from two long-term studies (ROADMAP and ORIENT) indicated a numerical imbalance in the number of cardiovascular deaths between the olmesartan medoxomil (OM) and placebo groups.
  
  
  OBJECTIVE
  Our objective was to conduct an individual patient data meta-analysis to provide more complete information regarding OM-associated cardiovascular risks and/or benefits.
  
  
  METHODS
  We created an integrated database based on 191 clinical trials from the OM development program. Events were identified and adjudicated by an independent, blinded clinical events committee. The incidence of major cardiovascular events and total mortality for OM versus placebo/active control were evaluated, and the effect of OM on cardiovascular mortality (main endpoint of interest) and morbidity was calculated using a two-stage approach (Tian method).
  
  
  RESULTS
  A total of 46 studies (~27,000 patients) met the US FDA-specified inclusion criteria (phase II-IV randomized, double-blind, placebo- or active-controlled studies [OM-based monotherapy or combination, double-blind period ≥28 days] and adult patients). The incidence of known adjudicated endpoints in the analysis of all studies combined was low among OM (0.11-0.53 %) and placebo/active control (0.08-0.76 %) groups. For cardiovascular mortality, the estimated risk difference (OM vs. control) was 0.00070 (95 % confidence interval [CI] -0.0011 to 0.0024; p = 0.60); the risk difference for each endpoint was <1/1000, with no statistically significant difference between groups. Results were similar with and without ROADMAP and ORIENT.
  
  
  CONCLUSIONS
  The results from this meta-analysis did not show a clinically meaningful or statistically significant difference in cardiovascular risk between OM and the placebo/active control groups, and thus did not corroborate the numerical imbalance observed in ROADMAP and ORIENT.
authors: Biostatistics, Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ, 08837, USA. awang@dsi.com.
authors: Antonia C
authors: AC
authors: Wang
authors: Daiichi Sankyo Europe GmbH, Munich, Germany.
authors: Ulf
authors: U
authors: Stellmacher
authors: Statistics Collaborative, Inc., Washington, DC, USA.
authors: Jennifer
authors: J
authors: Schumi
authors: Biostatistics, Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ, 08837, USA.
authors: Nora
authors: N
authors: Tu
authors: Daiichi Sankyo Europe GmbH, Munich, Germany.
authors: Paul-Egbert
authors: PE
authors: Reimitz
mesh_terms: D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002319:Cardiovascular System / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D006801:Humans; D000068557:Olmesartan Medoxomil / Q000009:adverse effects* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D000959:Antihypertensive Agents; D000068557:Olmesartan Medoxomil