title: Blood pressure and cardiovascular outcomes in patients taking nonsteroidal antiinflammatory drugs.
abstract: BACKGROUND
  The increased thrombotic cardiovascular (CV) risk in trials of cyclo-oxygenase-2 (COX-2) inhibitors versus placebo, and the apparent similar risk with nonsteroidal antiinflammatory drugs (NSAIDs), may be related to their potential to elevate blood pressure (BP).
  
  
  OBJECTIVE
  We evaluated the relationship between baseline BP and change in BP on CV events (CVEs) in patients receiving NSAIDs or COX-2 inhibitors in the prospective randomized, double-blind, Multinational Etoricoxib and Diclofenac Arthritis Long-term Program (N = 34,701) comparing etoricoxib 60 or 90 mg or diclofenac 150 mg daily for a mean duration of 18 months. The main outcome measure was confirmed thrombotic CVEs. The Antiplatelet Trialists' Collaboration endpoint, all-cause mortality, CV/congestive heart failure (CHF) mortality, and CHF incidence were similarly evaluated.
  
  
  RESULTS
  We found that baseline systolic BP (SBP) was associated with significantly higher risk of all events (P < 0.001). Baseline diastolic BP (DBP) was inversely and significantly associated with risk of all events (P < 0.001 to P = 0.016) except CV/CHF mortality (P = 0.054). There was no significant differential effect between etoricoxib and diclofenac in relation to CVEs, except for confirmed CHF, for which the risk was significantly higher with etoricoxib (P = 0.019). Only CHF risk (P = 0.020 for both SBP and DBP change), but not thrombotic endpoints, was significantly associated with change in BP from months 0 to 4. These findings were not meaningfully altered after covariate adjustment for baseline CV risk.
  
  
  CONCLUSIONS
  Baseline BP, but not change in BP, was significantly associated with risk of thrombotic CVEs through 18 months. The CV risk of COX-2s and NSAIDs did not appear to be related to the BP-elevating effects of these agents, although such analyses, i.e., from randomized controlled trials, are unable to definitively exclude such a relationship.
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. henry.krum@monash.edu
authors: Henry
authors: H
authors: Krum
authors: Gary
authors: G
authors: Swergold
authors: Arnold
authors: A
authors: Gammaitoni
authors: Paul M
authors: PM
authors: Peloso
authors: Steven S
authors: SS
authors: Smugar
authors: Sean P
authors: SP
authors: Curtis
authors: D Craig
authors: DC
authors: Brater
authors: Hongwei
authors: H
authors: Wang
authors: Amarjot
authors: A
authors: Kaur
authors: Loren
authors: L
authors: Laine
authors: Matthew R
authors: MR
authors: Weir
authors: Christopher P
authors: CP
authors: Cannon
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight; D015897:Comorbidity; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects; D004008:Diclofenac / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D000077613:Etoricoxib; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D044469:Racial Groups; D018570:Risk Assessment; D013450:Sulfones / Q000009:adverse effects* / Q000627:therapeutic use; D013927:Thrombosis / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011725:Pyridines; D013450:Sulfones; D004008:Diclofenac; D000077613:Etoricoxib