Clinical trials in neuromodulatory treatment of drug-resistant hypertension and the need for spinal cord stimulation trials: a PRISMA systematic review

Drug-resistant hypertension affects approximately 9-18% of the United States hypertensive population. Recognized as hypertension that is resistant to three or more medications, drug-resistant hypertension can lead to fatal sequelae, such as heart failure, aortic dissection, and other vast systemic disease. The disruption of the homeostatic mechanisms that stabilize blood pressure can be treated procedurally when medication fails. These procedures include carotid body stimulation, renal denervation, sympathectomies, dorsal root ganglia stimulation, and more recently spinal cord stimulation and have all been utilized in the treatment of drug-resistant hypertension. To identify the clinical trials of neuromodulation in drug-resistant hypertension, a PubMed search was performed that included all original clinical trials of neuromodulation treating drug-resistant hypertension. The 838 articles found were sorted using Covidence to find 33 unique primary clinical trials. There were no methods used to assess risk of bias as a meta-analysis was not feasible due to heterogeneity. Renal denervation and carotid body stimulation have both shown promising results with multiple clinical trials, while sympathectomies have mostly been retired due to the irreversible adverse effects caused. Dorsal root ganglion stimulation showed varying success rates. Spinal cord stimulation is a novel treatment of drug-resistant hypertension that shows promising initial results but requires further investigation and prospective studies of the treatment to provide guidelines for future DRH treatment. The limitations of the review are reporting bias and absence of a meta-analysis that compares the treatment modality due to the heterogeneity of reported outcomes. Innovation in neuromodulation is necessary to provide alternative avenues of treatment in the face of contraindications for standard treatment. Treatment of drug-resistant hypertension is essential to delay dangerous sequelae. This review's objective is to summarize the clinical trials for treatment of drug-resistant hypertension following PRISMA guidelines and suggests future directions in the treatment of drug-resistant hypertension.