Efficacy of Spinal Cord Stimulation in Patients With Refractory Angina Pectoris

Summary

There are a growing number of patients with refractory angina pectoris (RAP). RAP is defined as a 'chronic condition (\> three months) characterized by diffuse coronary artery disease in the presence of proven ischemia, which is not amendable to a combination of medical therapy, angioplasty or coronary bypass surgery'. These patients are severely restricted in performing daily activities due to debilitating angina complaints, leading to a decreased quality of life.

Spinal cord stimulation (SCS) is a last resort treatment option for patients with RAP. SCS is a device with a lead located in the thoracic epidural space and an Implantable Pulse Generator (IPG) in the abdomen or buttock that provides neurostimulation. Four possible mechanisms explaining the beneficial effects of SCS on RAP have been described: reduction of pain perception, decreased sympathetic tone, reduced myocardial oxygen demand, and improved coronary microcirculatory blood flow.

Research into the effect of SCS on RAP up to date have mainly been observational studies, with only four placebo-controlled randomized controlled trials. All studies confirm that treatment with SCS leads to a reduction in the number of angina pectoris attacks. What is currently not clear, is whether there is a placebo effect as results vary between the studies. One study looked at the effect of SCS in patients with RAP on the reduction of ischemia (using MIBI-SPECT) with no control arm. After 12 months myocardial ischemia was reduced, but not after three months of treatment. Leading to the conclusion that the reduction is myocardial ischemia was not a direct effect of SCS, but rather due to better coronary collateralization.

The 2020 ESC guideline 'chronic coronary syndromes' mentions non-existing to promising levels of evidence with regard to treatment options in patients with RAP and concludes that SCS may be considered (Class IIB; level of evidence B). It concludes that 'larger RCTs are required to define the role of each treatment modality for specific subgroups, to decrease non-responder rates and ascertain benefit beyond potential placebo effects'.

The aim of the current randomized controlled trial (double-blind, cross-over, placebo-controlled, single center) is to determine if high density spinal cord stimulation, a paresthesia free form of stimulation, leads to a significant reduction in myocardial ischemia (using PET with Rubidium-82 as tracer) in patients with refractory angina pectoris.

All patients included in this study will receive an implanted spinal cord stimulator after a positive TENS treadmill outcome and proven ischemia using the imaging modality PET with Rubidium-82 as tracer. Using a cross-over design all patients will have a 6 month period with high density stimulation and 6 month period of no stimulation. Randomization will determine in which order the patient receives these treatments. Both the patient and the treating physicians are blinded for this randomization process. At baseline a 6-minute walking test, the Seattle Angina Questionnaire, the RAND-36 questionnaire, the NRS scale and the CCS class will be performed/filled out.

Cross-over takes place at 6 months (switch from high density stimulation to no stimulation or vice versa) prior to which the PET scan is repeated, as well as the 6-minute walking test, the Seattle Angina Questionnaire, the RAND-36 questionnaire, the NRS-scale and the CCS-class.

At the end of the study period (12 months) the PET scan is repeated, as well as the 6-minute walking test, the Seattle Angina Questionnaire, the RAND-36 questionnaire, the NRS-scale and the CCS-class.

Conditions

• Refractory Angina Pectoris
• Spinal Cord Stimulation

Interventions

DEVICE

Spinal Cord Stimulator

All patients will receive an implanted spinal cord stimulator.

Sponsors & Collaborators

• Catharina Ziekenhuis Eindhoven

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-12-21

Primary Completion

2024-06-30

Completion

2025-06-30

Countries

• Netherlands

Study Locations