Takaisin Tulosta

The use of non-steroidal anti-inflammatory drugs and heart failure

Evidence summaries
Eero Mervaala, Markku Pentikäinen, Johan Lassus and Jyri Lommi
30.10.2017

Level of evidence: A

The use of non-steroidal anti-inflammatory drugs increases the risk of worsening of heart failure and admission for congestive heart failure.

Meta-analyses «Scott PA, Kingsley GH, Scott DL. Non-steroidal ant...»1 examining the risks of developing cardiac failure in observational studies and in randomized controlled trials (RCTs) involving patients with arthritis and non-rheumatic disorders was performed. Electronic databases and published bibliographies were systematically searched (1997–2008).

Five case–control studies (4657 patients, 45,862 controls) showed a non-significant association between NSAIDs and cardiac failure in a random effect model (odds ratio (OR) 1.36; 95% CI 0.99–1.85). Two cohort studies (27,418 patient years, 55,367 control years) showed a significant risk of cardiac failure with NSAIDs (relative risk 1.97; 95% CI 1.73–2.25). Six placebo-controlled trials (naproxen, rofecoxib and celecoxib) in non-rheumatic diseases (15,750 patients) showed more cardiac failure with NSAIDs (OR 2.31; 95% CI 1.34, 4.00). Six RCTs comparing conventional NSAIDs and COXIBs in arthritis (62,653 patients) showed no difference in cardiac failure risk (OR 1.14; 95% CI 0.85–1.53).

Observational studies and RCTs all show that NSAIDs increase the risk of cardiac failure. Overall risks are relatively small and are similar with conventional NSAIDs and COXIBs. Pre-existing cardiac failure increases risk.

  • Study quality: High
  • Applicability: Good

In the population-based retrospective cohort study «Mamdani M, Juurlink DN, Lee DS ym. Cyclo-oxygenase...»2 the authors identified NSAID-naive individuals aged 66 years or older, who were started on rofecoxib (n=14,583), celecoxib (n=18,908), and non-selective NSAIDs (n=5,391), and randomly selected non-NSAID users as controls (n=100,000).

Relative to non-NSAID users, patients on rofecoxib and non-selective NSAIDS had an increased risk of admission for congestive heart failure (adjusted rate ratio 1·8, 95% CI 1·5–2·2, and 1·4, 1·0–1·9, respectively), but not celecoxib (1·0, 0·8–1·3). Compared with celecoxib users, admission was significantly more likely in users of nonselective NSAIDs (1·4, 1·0–1·9) and rofecoxib (1·8, 1·4–2·4). Risk of admission for rofecoxib users was higher than that for non-selective NSAID users (1·5, 1·1–2·1). Of patients with no admission in the past 3 years, only rofecoxib users were at increased risk of subsequent admission relative to controls (1·8, 1·4–2·3).

It was concluded that these findings suggest a higher risk of admission for congestive heart failure in users of rofecoxib and non-selective NSAIDs, but not celecoxib, relative to non-NSAID controls.

  • Study quality: Moderate
  • Applicability: Good

Ungprasert and coworkers conducted a systematic review and meta-analysis of observational studies «Ungprasert P, Srivali N, Kittanamongkolchai W. Non...»3 that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of incident HF in NSAID users vs nonusers. Pooled risk ratios (RR) and 95% confidence intervals (CI) for all NSAIDs and both subclasses (conventional NSAIDs and highly selective cyclooxygenase-2 inhibitors [COXIBs]) were calculated using a random-effect, generic inverse variance method.

Seven studies with 7 543 805 participants were identified and included in the data analysis. Use of NSAIDs was associated with a significantly higher risk of developing HF, with a pooled RR of 1.17 (95% CI: 1.01-1.36). Subgroup analysis showed a significantly elevated risk among users of conventional NSAIDs (RR: 1.35, 95% CI: 1.15-1.57) but not users of COXIBs (RR: 1.03, 95% CI: 0.92-1.16).

Conclusions: A significantly elevated risk of incident HF was observed among users of NSAIDs.

  • Study quality: High
  • Applicability: Good

Cohort study «Huerta C, Varas-Lorenzo C, Castellsague J ym. Non-...»4 with a nested case–control analysis based on the UK General Practice Research Database. Overall, 1396 cases of first hospital admission for non-fatal HF were identified (January 1997 to December 2000) and compared with a random sample of 5000 controls.

The HF incidence rate was 2.7/1000 person years. Prior clinical diagnosis of HF was the main independent risk factor triggering a first HF hospitalisation (relative risk 7.3, 95% confidence interval (CI) 6.1 to 8.8). The risk of a first hospital admission for HF associated with current use of NSAIDs was 1.3 (95% CI 1.1 to 1.6) after controlling for major confounding factors. No effects of dose and duration were found. The relative risk in current users of NSAIDs with prior HF was 8.6 (95% CI 5.3 to 13.8) compared with patients who did not use NSAIDs and without prior clinical diagnosis of HF.

Use of NSAIDs was associated with a small increase in risk of a first hospitalisation for HF. In patients with prior clinical diagnosis of HF, the use of NSAIDs may lead to worsening of pre-existing HF that triggers their hospital admission. This increased risk, although small, may result in considerable public health impact, particularly among the elderly.

  • Study quality: Moderate
  • Applicability: Good

References

  1. Scott PA, Kingsley GH, Scott DL. Non-steroidal anti-inflammatory drugs and cardiac failure: meta-analyses of observational studies and randomised controlled trials. Eur J Heart Fail 2008;10:1102-7 «PMID: 18760966»PubMed
  2. Mamdani M, Juurlink DN, Lee DS ym. Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study. Lancet 2004;363:1751-6 «PMID: 15172772»PubMed
  3. Ungprasert P, Srivali N, Kittanamongkolchai W. Non-steroidal anti-inflammatory drugs and risk of heart failure exacerbation: A systematic review and meta-analysis. Eur J Intern Med 2015;26:685-90 «PMID: 26427540»PubMed
  4. Huerta C, Varas-Lorenzo C, Castellsague J ym. Non-steroidal anti-inflammatory drugs and risk of first hospital admission for heart failure in the general population. Heart 2006;92:1610-5 «PMID: 16717069»PubMed