Spinal cord stimulation for the treatment of painful diabetic neuropathy and risk of major adverse cardiovascular events, mortality, amputation, infection and suicide: a retrospective cohort study.

Background: Spinal cord stimulation (SCS) has recently been approved by the US Food and Drug Administration (FDA) for the treatment of refractory painful diabetic neuropathy (PDN), although the current evidence for efficacy is limited by small sample sizes and short follow-up. We aimed to assess the benefits of SCS, compared to combination pharmacotherapy (gabapentinoid plus duloxetine), in a large population of PDN patients using real-world evidence. Methods: We performed a real-world cohort study of electronic medical records using the TriNetX network, a global federated database (9th September 2024). The treatment arm was patients with PDN (defined as diabetes plus neuropathic pain treatment) treated with SCS (refractory to pharmacotherapy), compared against a reference arm of patients treated with gabapentinoid and duloxetine combination therapy. We propensity score matched (1:1) for confounders with 3 years of follow-up. The primary outcome was time-to incident major adverse cardiovascular event (MACE, that is, a composite outcome of non-fatal ischaemic heart disease, cerebrovascular accident or heart failure, or sudden cardiac death) and secondary outcomes included time-to all-cause mortality, below-knee amputation (BKA), suicide (suicidal ideation and/or attempt), staphylococcus aureus infection, major adverse kidney events (end stage renal failure and/or dialysis), diabetes-related ophthalmic disease (retinopathy and/or maculopathy), hospitalisation and SCS explantation. All outcomes were assessed using ICD-10/CPT codes. Stratified analyses assessed the impact of sex, ethnicity, age, geographic location (USA) and discontinuation of analgesia post SCS implantation on these outcomes. Findings: We identified 145,380 patients, with 3212 treated with SCS and 142,168 treated with dual pharmacotherapy alone. After PSM, 3105 patients were included in each arm. Treatment with SCS significantly reduced the risk of MACE (hazard ratio 0.57 [95% CI 0.49, 0.67]), all-cause mortality (0.49 [0.39, 0.62]), BKA amputation (0.19 [0.08, 0.46]), suicide (0.36 [0.22, 0.59]), staphylococcus aureus infection (0.67 [0.51, 0.90]), MAKE (0.46 [0.27, 0.79]), diabetes-related ophthalmic disease (0.33 [0.23, 0.48]) and hospitalisation (0.59 [0.53, 0.66]), compared with combination pharmacotherapy. 11.1% of SCS patients underwent explant. Female and older patients had greater reductions in BKA and infection with SCS, whilst the associated reduced risk of suicide was most prominent in younger adults. Interpretation: Our results suggest that SCS treatment of PDN is associated with a reduced risk of MACE, all-cause mortality, major amputation, suicide, and staphylococcus aureus infection. The findings provide evidence for the putative benefits of SCS as treatment for PDN. Prospective sham controlled RCTs with pain endpoint whilst incorporating longer term follow-up of CV/mortality outcomes are needed to confirm the benefits and explore cost-effectiveness of SCS. Funding: None.