Key result
Ivabradine fails to reduce daily pain scores from baseline in chronic peripheral neuropathic pain.
Why the study?
Preclinical studies suggest a critical role of HCN2 ion channels in neuropathic pain and ivabradine may have analgesic potential in chronic peripheral neuropathic pain patients.
Does ivabradine reduce pain scores in patients with chronic peripheral neuropathic pain?
Does ivabradine reduce pain scores in patients with chronic peripheral neuropathic pain?
Mean Difference: -0.878 (95% CI -2.07–0.31)
Absolute Event Rate: 4.52% vs 5.39%
p-value: p=0.100
In a small proof-of-concept study, ivabradine did not significantly reduce chronic peripheral neuropathic pain overall, though exploratory analyses suggest a dose-dependent analgesic effect that warrants further investigation.
Introduction: Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels mediate repetitive action potential firing in the heart and nervous system. The HCN2 isoform is expressed in nociceptors, and preclinical studies suggest a critical role in neuropathic pain. Ivabradine is a nonselective HCN blocker currently available for prescription for cardiac indications. Mouse data suggest that ivabradine in high concentrations is equianalgesic with gabapentin. We sought to translate these findings to patients with chronic peripheral neuropathic pain. Objectives: We sought to translate these findings to patients with chronic peripheral neuropathic pain. Methods: We adopted an open-label design, administering increasing doses of ivabradine to target a heart rate of 50 to 60 BPM, up to a maximum of 7.5 mg twice daily. All participants scored their pain on an 11-point numerical rating scale (NRS). Results: Seven (7) participants received the drug and completed the study. There was no significant treatment effect on the primary endpoint, the difference between the mean score at baseline and at maximum dosing (mean reduction = 0.878, 95% CI = −2.07 to 0.31, P = 0.1). Exploratory analysis using linear mixed models, however, revealed a highly significant correlation between ivabradine dose and pain scores (χ2(1) = 74.6, P < 0.001), with a reduction of 0.12 ± 0.01 (SEM) NRS points per milligram. The 2 participants with painful diabetic neuropathy responded particularly well. Conclusion: This suggests that ivabradine may be efficacious at higher doses, particularly in patients with diabetic neuropathic pain. Importantly, participants reported no adverse effects. These data suggest that ivabradine, a peripherally restricted drug (devoid of central nervous system side effects), is well tolerated in patients with chronic neuropathic pain. Ivabradine is now off-patent, and its analgesic potential merits further investigation in clinical trials.
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Healey et al. (2021) studied Chronic peripheral neuropathic pain (n=7). Ivabradine vs. Baseline was evaluated on Change from baseline in mean daily NRS pain score after dosing (MD -0.878, 95% CI -2.07 to 0.31, p=0.100). Ivabradine did not significantly reduce mean daily pain scores compared to baseline in patients with chronic peripheral neuropathic pain (mean difference -0.878, p=0.100).
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