Effect of opioids for breathlessness in heart failure: a systematic review and meta-analysis

BackgroundFor the treatment of breathlessness in heart failure (HF), most textbooks advocate the use of opioids. Yet, meta-analyses are lacking. MethodsA systematic review was performed for randomised controlled trials (RCTs) assessing effects of opioids on breathlessness (primary outcome) in patients with HF. Key secondary outcomes were quality of life (QoL), mortality and adverse effects. Cochrane Central Register of Controlled Trials, MEDLINE and Embase were searched in July 2021. Risk of bias (RoB) and certainty of evidence were assessed by the Cochrane RoB 2 Tool and Grading of Recommendations Assessment, Development and Evaluation criteria, respectively. The random-effects model was used as primary analysis in all meta-analyses. ResultsAfter removal of duplicates, 1180 records were screened. We identified eight RCTs with 271 randomised patients. Seven RCTs could be included in the meta-analysis for the primary endpoint breathlessness with a standardised mean difference of 0.03 (95% CI -0.21 to 0.28). No study found statistically significant differences between the intervention and placebo. Several key secondary outcomes favoured placebo: risk ratio of 3.13 (95% CI 0.70 to 14.07) for nausea, 4.29 (95% CI 1.15 to 16.01) for vomiting, 4.77 (95% CI 1.98 to 11.53) for constipation and 4.42 (95% CI 0.79 to 24.87) for study withdrawal. All meta-analyses revealed low heterogeneity (I-2 in all these meta-analyses was <8%). ConclusionOpioids for treating breathlessness in HF are questionable and may only be the very last option if other options have failed or in case of an emergency. PROSPERO registration numberCRD42021252201.

Automated summary

For the treatment of breathlessness in heart failure, opioids are commonly recommended but lack strong evidence. This systematic review of randomized controlled trials suggests that opioids have limited efficacy and may cause adverse effects. Therefore, opioids should be considered as a last resort and only used when other treatments have failed or in emergencies.