Does the presence of a hiatal hernia affects the efficacy of the reflux inhibitor baclofen?
H. Beaumont1, G.E.E. Boeckxstaens1,2
Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands 1;
Department of Gastroenterology, University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium 2
Reflux inhibitors like the GABAB receptor agonist baclofen, block transient lower esophageal
sphincter relaxations (TLESRs) and are proposed as add-on therapy in patients with PPI
resistant symptoms. However, as other mechanisms of gastroesophageal reflux become more
important in the presence of a hiatal hernia (HH), the efficacy of reflux inhibitors to reduce
acid and non-acid reflux may be hampered. Therefore, we compared the effect of baclofen on
gastroesophageal reflux during PPI treatment in patients with no HH and those with a large
HH. 27 GERD patients on PPI were included in the study (15M, median age 54) of which 16
had no HH (–HH, 8M, median age 54) and 11 had a large HH  3 cm (+HH, 7M, median age
58). During PPI treatment, the effect of baclofen (3x20mg) on acid and non-acid reflux was
evaluated in a randomized, double-blind, placebo controlled cross-over study. Reflux was
measured during 24 hrs using combined esophageal impedance and pH metry, with the pH
electrode 5cm above the proximal margin of the LES. HH size measured 3.6±0.3cm in +HH
patients. After placebo, a total of 694 and 1157 reflux episodes were recorded in –HH and
+HH patients, respectively. Baclofen significantly reduced the total amount of reflux episodes
with 32% in –HH patients (from 56 (43-66)/patient to 40 (27-50)/patient, p<0.01) and with
43% in +HH patients (from 95 (87-141)/patient to 69 (32-74)/patient, p=0.003). This decrease
was mainly due to reduction of non-acid reflux episodes in both –HH patients (from 45 (1759)/patient to 29 (22-35)/patient, p<0.03) and +HH patients (from 79 (54-121)/patient to 38
(39-61)/patient, p=0.003). Furthermore, baclofen significantly reduced the rate of reflux
episodes extending into the proximal esophagus in both –HH (placebo: 182 (9 (6-16)/patient);
baclofen: 119 (6 (2-12)/patient), p<0.05) and +HH patients (placebo: 246 (21 (5-40)/patient);
baclofen: 116 (15 (2-19)/patient), p=0.005). Acid exposure time was in the normal range in
both groups during placebo and was not significantly changed by baclofen. Somnolence was
most commonly reported as side effect after baclofen. All side effects were of mild to
moderate intensity. This study demonstrates that baclofen is also effective in reducing PPI
resistant reflux, particularly non-acid reflux, in GERD patients with a large HH. These
findings further strengthen the therapeutic potential for reflux inhibitors as add-on therapy in
GERD patients with incomplete response to acid suppression.