title: Selective COX-2 inhibitors, NSAIDs and congestive heart failure: differences between new and recurrent cases.
abstract: BACKGROUND
  Pharmaco-epidemiological studies have shown that in susceptible individuals, nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors increase the risk of developing congestive heart failure (CHF). Recently published studies have found lower relative risk (RR) estimates than the initial studies published in 1998-2000. It is unclear whether the level of risk is elevated equally in first time and recurrent cases of CHF.
  
  
  CONCLUSIONS
  This study found low-level, statistically nonsignificant elevations of risk with NSAIDs and COX-2 inhibitors. There was a much higher level of recent use of NSAIDs/COX-2 inhibitors among first-time cases than among recurrent cases of CHF. * The dilution of the RR over successive studies, and the differences between first-time and recurrent cases noted here, suggest that prescribing doctors have heeded advice about the cardiovascular risks of NSAIDs and extended this practice to selective COX-2 inhibitors.
  
  
  OBJECTIVE
  To quantify the association between treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors and hospitalization due to congestive heart failure (CHF); to determine if the risk varies between first and subsequent episodes of CHF.
  
  
  METHODS
  We conducted a case-control study of the relationship between recent use of NSAIDs and COX-2 inhibitors and hospitalization with CHF. Cases (n = 530) were patients admitted to hospital with a primary diagnosis of CHF. Controls (n = 1054) were subjects without CHF who were admitted to the same hospitals as the cases. They were frequency matched to cases on the basis of age and sex. Structured interviews were used to obtain information on a number of study factors, including recent use of NSAIDs and COX-2 inhibitors. Relative risks (RRs) were estimated from exposure odds ratios, adjusted for a range of potential confounders.
  
  
  RESULTS
  Overall, NSAIDs and COX-2 inhibitors had been taken by 249 (23.6%) controls in the week before admission to hospital. Use of any NSAID/COX-2 inhibitor was recorded in 81/285 (28.4%) first-time cases compared with 38/245 (15.5%) in recurrent cases: difference 12.9% (95% confidence interval 5.9, 19.8) (P = 0.0004). The adjusted RRs for first hospital admission for CHF with different drug exposures were: NSAIDs 1.1 (0.67, 1.83), rofecoxib 1.29 (0.78, 2.13) and celecoxib 1.47 (0.85, 2.53).
  
  
  CONCLUSIONS
  We found weak and statistically nonsignificant associations between use of NSAIDs and COX-2 inhibitors and hospitalization with CHF. This low RR is consistent with the results of recently published studies, but not with early studies that found an approximate doubling of risk with use of NSAIDs. The dilution of risk and the significantly lower levels of prescribing for recurrent than for first-time cases of heart failure suggest that prescribing doctors heeded messages that NSAIDs may precipitate CHF in vulnerable individuals, and that they have applied the same message to selective COX-2 inhibitors.
authors.affiliation: Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: McGettigan
authors.forename: Pearline
authors.initials: P
authors.lastname: Han
authors.forename: Lisa
authors.initials: L
authors.lastname: Jones
authors.forename: Diana
authors.initials: D
authors.lastname: Whitaker
authors.forename: David
authors.initials: D
authors.lastname: Henry
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007783:Lactones / Q000009:adverse effects; D008297:Male; D011720:Pyrazoles / Q000009:adverse effects; D012008:Recurrence; D012307:Risk Factors; D013223:Statistics as Topic; D013449:Sulfonamides / Q000009:adverse effects; D013450:Sulfones / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D000068579:Celecoxib