Electrical stimulation of the lower oesophageal sphincter for treating gastro-oesophageal reflux disease

A case series of 44 patients with gastro‑oesophageal reflux disease (GORD) treated by electrostimulation of the lower oesophageal sphincter (LOS) reported median (interquartile range; IQR) percentages of days with heartburn of 86% (64 to 100%, n=35) before the procedure and 17% (0 to 93%, n=34) at 6 months (p<0.0001). Median (IQR) percentages of nights with heartburn were 64% (43 to 86%, n=35) before the procedure and 0% (0 to 8%, n=34) at 6 months (p<0.0001). The evaluations used a symptom diary kept by the patients. A case series of 25 patients with GORD treated by electrostimulation of the LOS, with a 2‑year follow‑up, reported median percentages of days and nights with heartburn at 'baseline off proton pump inhibitors (PPIs)' (defined as 10 days after the patients had started electrostimulation and had stopped taking PPIs) and at follow‑up. Median percentages of days with heartburn were 92% at 'baseline off PPIs', 14% at 6 months, 13% at 12 months and 7% at 24 months (p<0.001 for all times versus 'baseline off PPIs'). Median percentages of nights with heartburn were 71% at 'baseline off PPIs', and 0% at 6, 12 and 24 months (p<0.001 for all times versus 'baseline off PPIs').

The case series of 44 patients reported median (IQR) percentages of days with regurgitation of 79% (54 to 100%, n=35) before the procedure and 0% (0 to 21%, n=34) at 6 months (p<0.0001). Median (IQR) percentages of nights with regurgitation were 50% (15 to 79%, n=35) before the procedure and 0% (0 to 7%, n=34) at 6 months (p<0.0001). The case series of 25 patients reported median percentages of days with symptoms of regurgitation of 66% at 'baseline off PPIs', and 0% at 6, 12 and 24 months (p<0.001 for all times versus 'baseline off PPIs'). Median percentages of nights with regurgitation were 31% at 'baseline off PPIs', and 0% at 6, 12 and 24 months (p<0.01 for all times versus 'baseline off PPIs').

The case series of 25 patients reported dysphagia caused by GORD in 38% (9/24) of patients at 'baseline on PPIs' and in 71% (17/24) at 'baseline off PPIs'. Dysphagia was reported in 13% (n=23) of patients at 12‑month follow‑up, and in 5% (1/21) at 24‑month follow‑up (level of significance not stated).

The case series of 44 patients reported median gastro‑oesophageal reflux disease health‑related quality of life (GORD‑HRQL) scores (IQR) at baseline of 16.5 (9.0 to 22.8) when patients (n=42) were still taking PPIs and of 31.0 (26.2 to 36.8) when patients (n=42) had stopped taking PPIs. The scores improved significantly to 5.0 (3.0 to 9.0) at 6 months, (n=41, p<0.0001 for the comparison against 'baseline on PPI' and 'baseline off PPI' scores). The case series of 25 patients reported median GORD‑HRQL scores (IQR) at baseline of 9.0 (6.0 to 10.0) when patients (n=24) were still taking PPIs, and of 23.5 (21.0 to 25.8) when patients (n=24) had stopped taking PPIs. The scores improved significantly to 2.0 at 12 months (IQR and number of patients not given) and to 0 (0 to 3.0) at 24 months (n=21; p≤0.002 versus 'baseline on PPI' and 'baseline off PPI' scores at 12- and 24‑month follow‑up respectively). A publication reporting on 15 patients from the case series of 25 patients with GORD treated by electrostimulation of the LOS after 3 years of follow‑up, reported median GORD‑HRQL scores (IQR) at baseline of 9.0 (6.0 to 10.0) when patients were still taking PPIs and of 23.5 (21.0 to 25.0) when patients had stopped taking PPIs. The scores improved significantly to 1.0 (0.0 to 2.0) at 3 years (p<0.001).

In the case series of 44 patients, 74% (31/42) of patients reported dissatisfaction with GORD control at 'baseline on PPIs' and 21% (8/39) reported it 6 months after the procedure. In the case series of 25 patients, 71% (17/24) of patients reported dissatisfaction with GORD control at 'baseline on PPIs' and 92% (22/24) reported dissatisfaction at 'baseline off PPIs'. At 24‑month follow‑up, dissatisfaction was reported in none (0/21) of the patients (p<0.001 for both groups of patients).

The case series of 25 patients reported that GORD had an impact on their sleep in 71% (17/24) of patients at 'baseline on PPIs' and in 96% (23/24) of patients at 'baseline off PPIs'. At 12‑month follow‑up, GORD was reported to have an impact on their sleep by 17% of patients (n=23, absolute numbers not given) and, at 24‑month follow‑up, by 10% (2/21) of patients.

The case series of 44 patients reported that the median (IQR) percentages of the 24‑hour period for which there was a distal oesophageal pH of less than 4 was 10% (8 to 13%, n=42) before the procedure compared against 4% (2 to 7%, n=40) after 6 months (p<0.0001). The case series of 25 patients reported that the median percentage of the 24‑hour period for which there was a distal oesophageal pH of less than 4 was 10% (IQR 8 to 13%) at baseline (n=24; defined for this measure as at least 5 days after the patients had started electrostimulation and had stopped taking PPIs) compared against 5% (3 to 7%) at 24 months (n=18; p=0.001 versus baseline). At baseline, 96% (23/24) of patients had an abnormal distal oesophageal pH (less than 4 for more than 4% of a 24‑hour recording) and, at 24 months, 61% (11/18) had an abnormal pH. The publication reporting on 15 patients from the case series of 25 patients with a 3‑year follow‑up reported that the median (IQR) percentages of the 24‑hour period for which there was a distal oesophageal pH of less than 4 was 10% (8 to 12%) at baseline compared against 3% (2 to 5%) at 3 years (p<0.001 for the comparison against baseline scores).

In the case series of 44 patients, 90% (37/41) of patients were completely off PPI, 5% (2/41) reported intermittent use of PPIs and 7% (3/41) reported regular use of PPIs at 6 months (p<0.001). In the case series of 25 patients, all patients still included in the study (24/24) were taking PPIs for GORD after implantation. At 24 months, 76% (16/21) of patients were not taking any PPIs, 14% (3/21) reported occasional PPI use and 10% (2/21) reported regular PPI use. The publication reporting on 15 patients from the case series of 25 patients with a 3‑year follow‑up reported that 73% of patients were free from PPI dependence (defined as 50% or more diary days with PPI use) at 3 years.

The case series of 44 patients reported that, at baseline, 41% (16/39) of patients had no oesophagitis, 31% (12/39) had Los Angeles classification (LA) grade A oesophagitis (grades A to D range from less severe to more severe oesophagitis assessed by endoscopy), 23% (9/39) had LA grade B oesophagitis and 5% (2/39) had LA grade C oesophagitis. At 6 months, 51% (20/39) of patients had no oesophagitis, 31% (12/39) had LA grade A, 18% (7/39) had LA grade B and none (0/39) had LA grade C oesophagitis (p=0.02 for the improvement in oesophagitis grade at 6 months). A publication about the case series of 25 patients with GORD treated by electrostimulation of the LOS after only 1 year of follow‑up reported that, at baseline (within 6 months before enrolment), 67% (16/24) of patients had LA grade A oesophagitis, 25% (6/24) had LA grade B and 8% (2/24) had LA grade C oesophagitis. At 12 months, 31% (7/23) of patients had no oesophagitis, 52% (12/23) had LA grade A, 13% (3/23) had LA grade B and 4% (1/23) had LA grade C oesophagitis (p=0.01). Oesophagitis had improved by at least 1 grade in 58% (14/24) of patients at 3 months and in 57% (13/23) of patients at 12 months compared against baseline. The publication reporting on 15 patients from the case series of 25 patients with a 3‑year follow‑up reported that 50% (6/12) of the patients who had an endoscopy at 3 years showed an improvement in their oesophagitis by more than 1 grade.

The specialist advisers listed the following key efficacy outcomes: reduction in symptoms of acid reflux, elimination (remission) of pre‑operative GORD‑related symptoms assessed by GORD‑HRQL questionnaire, subjective and objective maintenance of remission, healing of any pre‑operatively noted oesophagitis (assessed according to LA grading), improved 24‑hour ambulatory pH studies, and lack of side effects such as dysphagia, bloating, fullness, increased wind and abdominal pain.