2018 Section 6 - Laryngology, Voice Disorders, and Bronchoesophalogy

Long-term safety of PPI therapy

Table 2 | Number of patients (%) with the most commonly reported serious adverse events (SAEs) in patients treated with omeprazole or open anti-re fl ux surgery (open ARS) in the SOPRAN study (cut-off ≥ 3 SAEs in any of the groups). The SAEs are presented by preferred term and in order from most to least common among patients receiving omeprazole

Table 3 | Number of patients (%) with the most commonly reported serious adverse events (SAEs) in patients treated with esomeprazole or laparoscopic anti-re fl ux surgery (LARS) in the LOTUS study (cut-off ≥ 3 SAEs in any of the groups). The SAEs are presented in order from most to least common among patients receiving esomeprazole

SAE (preferred term) Number of patients

Open ARS Omeprazole

SAE (preferred term) Number of patients

LARS

Esomeprazole

n = 144

n = 154

n = 248

n = 266

Total number of person-years

1324

1518

Total number of patient-years

1046

1067

Myocardial infarction

2 (1.4) 6 (4.2) 3 (2.1) 3 (2.1) 3 (2.1) 0 (0.0) 8 (5.6) 5 (3.5) 4 (2.1) 4 (2.8) 3 (2.1) 2 (1.4) 0 (0.0) 0 (0.0) 3 (2.1) 9 (6.2) 5 (3.5) 3 (2.1) 3 (2.1) 14 (9.7) 5 (3.5)

10 (6.5) 7 (4.5) 7 (4.5) 6 (3.9) 6 (3.9) 5 (3.2) 4 (2.6) 4 (2.6) 4 (2.6) 3 (2.0) 3 (2.0) 3 (2.0) 3 (2.0) 3 (2.0) 2 (1.3) 1 (0.6) 1 (0.6) 1 (0.6) 1 (0.6) 0 (0.0) 0 (0.0) 0 (0.0)

Myocardial infarction* Noncardiac chest pain

5 (2.0) 3 (1.2) 1 (0.4) 1 (0.4) 1 (0.4) 1 (0.4) 4 (1.6) 4 (1.6) 3 (1.2) 3 (1.2) 3 (1.2) 0

5 (1.9) 5 (1.9) 4 (1.5) 4 (1.5) 3 (1.1) 3 (1.1) 3 (1.1) 2 (0.8)

Angina pectoris

Chest pain

Musculoskeletal chest pain

Injury

Pancreatic carcinoma

Osteoarthritis

Angina pectoris Gastroenteritis

Cerebral infarction Abdominal pain

Pneumonia

Inguinal hernia Cardiac failure*

Osteoarthritis

Post-procedural complication

0 0 0 0

Pneumonia

Cholelithiasis

Transient ischaemic attack

Incisional hernia Procedural pain

Cholelithiasis Appendicitis

* Including three myocardial infarctions which were found in the surgical group during speci fi c follow-up of patients.

Syncope

Gastrointestinal haemorrhage

Postoperative infection

Intervertebral disc herniation

Hernia NOS Pancreatitis

study than in the LOTUS study, probably owing to dif- ferences in the assay procedures used. Vitamin D (LOTUS study only) remained constant and similar between treatment groups. Scatterplots for individual patients from baseline to last value (SOPRAN study) or 5 years (LOTUS study), shown in Figure 3 for ALP lev- els and in Figure 4 for calcium levels, revealed no extreme values. Creatinine levels did not change over time (data not shown). Haematological and nutrient markers No clinically relevant changes were noted in haematolog- ical variables over the study periods, either within each treatment group or between treatment groups. Individual abnormal values were found for most haematological variables (data not shown), but none were considered by the investigators to be clinically important. Haemoglobin, ferritin and vitamin B 12 levels remained constant (Table 1), as did levels of iron and homocysteine (mea- sured only in the LOTUS study). Folate levels in the SOPRAN study were quite constant in both groups (Table 1; folate data from the LOTUS study had a simi- lar pattern to that from the SOPRAN study but are not presented owing to issues regarding the compatibility of the data reporting). There was a similar, marginal

Postoperative hernia

Anaemia

Gastric ulcer

3 (2.1)

NOS, not otherwise speci fi ed. *Including one case of cardiac failure which was found in the surgical group during speci fi c follow-up of patients.

dural complication SAEs in the LOTUS laparoscopic ARS group.

Bone fractures and biomarkers for bone turnover There was one femur fracture reported in each treatment arm (PPI and ARS therapy) in both the SOPRAN study and the LOTUS study (four in total). One patient reported a concurrent pelvic fracture. In total across both studies, there were four additional reported fractures (skull, radius, distal foot and patella) distributed evenly across the PPI and ARS treatment arms. Ionised calcium levels remained constant over 5 years in both studies, with no difference between treatment groups (Table 1). Similarly, ALP levels remained con- stant and similar between treatment groups, although absolute levels were higher in patients in the SOPRAN

Aliment Pharmacol Ther 2015; 41: 1162 – 1174 ª 2015 John Wiley & Sons Ltd

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