Key result
Opioids did not significantly improve breathlessness compared to placebo in patients with heart failure (SMD 0.03, 95% CI -0.21 to 0.28), but significantly increased adverse events like nausea.
Why the study?
Most textbooks advocate the use of opioids for treating breathlessness in heart failure, yet meta-analyses were lacking.
Do opioids improve breathlessness in patients with heart failure?
Meta-Analysis (n=271)
Do opioids improve breathlessness in patients with heart failure?
Standardized Mean Difference: 0.03 (95% CI -0.21–0.28)
Opioids do not significantly improve breathlessness in heart failure patients but significantly increase the risk of adverse gastrointestinal effects.
Opioids confer no breathlessness relief in HF yet increase adverse events; confirms lack of efficacy and supports avoiding use in practice and trials.
Background For the treatment of breathlessness in heart failure (HF), most textbooks advocate the use of opioids. Yet, meta-analyses are lacking. Methods A 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. Results After 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%). Conclusion Opioids 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 number CRD42021252201.
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Gaertner et al. (2023) conducted a meta-analysis in Heart failure with refractory breathlessness (n=271). Opioids vs. Placebo was evaluated on Breathlessness (SMD 0.03, 95% CI -0.21 to 0.28). Opioids did not significantly improve breathlessness compared to placebo in patients with heart failure (SMD 0.03, 95% CI -0.21 to 0.28), but significantly increased adverse events like nausea.
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