Repeat Dose Opioids May Be Effective for Breathlessness in Chronic Heart Failure if Given for Long Enough

Background: The longer-term effects of opioids for breathlessness are not known in people with chronic heart failure (CHF). Objective: Our aim was to assess the longer-term effect of oral opioids on breathlessness due to CHF. Methods: We conducted a 3-month open-label extension to a crossover randomized controlled trial (RCT) comparing 4 days of morphine, oxycodone, and placebo. Thirty-five participants from a tertiary cardiology clinic completed the RCT. Thirty-three were followed for 3 months, continuing open-label opioids if they wished. Thirteen participants continued an opioid; 20 did not. Four measures of breathlessness intensity (0-10 numerical rating scale [NRS] and modified Borg score, each recording worst and average breathlessness during 24 hours) were combined using principal component analysis to give a single measure for the primary analysis. Groups were compared using analysis of covariance. Secondary measures included quality of life (SF-12 (R) Health Survey), cardiorespiratory, and global impression of change in breathlessness at 3 months. Results: At 3 months, the composite breathlessness measure improved to a greater extent in the opioid group (p = 0.017). The opioid group had an improvement in global impression of change (mean 2.62 [ opioids] versus -0.65 [nonopioids]; p = 0.0009). The SF-12 physical component improved more in the opioid group (p = 0.014). Cardiorespiratory variables were unchanged. Conclusions: Opioids given for 3 months were well tolerated and safe. Opioid-related improvement in breathlessness in people with CHF might not be seen until longer-term administration. We cannot conclude from these data that they are effective and a longer-term RCT is needed.