ONLINE EDITION Does Ivabradine Benefit patients with or without diabetes. At When PPI Therapy Cures Diabetic Patients with Stable baseline, the resting heart rate was Chronic Diarrhea, Suspect greater in those with diabetes, but Angina? both groups experienced a similar ZES heart rate reduction with ivabradine The novel antianginal drug ivabra- treatment. Additionally, the anti- Zollinger-Ellison syndrome (ZES), a dine, which was approved for use in anginal and anti-ischemic efficacy of rare condition caused by a gastrin Europe in 2005 but has not been FDA ivabradine was proportionately simi- secreting tumor of duodenopancre- approved to date, lowers the heart lar in both groups, indicating that dia- atic origin, is notoriously hard to rate through selective inhibition of betes does not have a negative effect. diagnose. But clinicians should sus- the heart’s If current. Previous studies Ivabradine treatment also reduced pect this syndrome, say physicians demonstrated the drug’s efficacy and angina attack frequency similarly from Saarland University Hospital, safety in managing stable coronary (by more than half) in both groups, Hamburg, Germany, when chronic, artery disease (CAD) to be compa- despite the fact that participants with unexplained diarrhea is alleviated by rable to that of the beta-blocker ateno- diabetes had a slightly lower fre- proton pump inhibitor (PPI) therapy. lol and the calcium channel blocker quency at baseline. They report the case of a patient amlodipine. But does this hold true Since the numbers of patients who who presented for evaluation after specifically for patients with diabetes? received the comparator drugs were three years of chronic, painless diar- To find out, researchers from State much smaller than the number of rhea. During that time, he had passed University of New York Downstate those who received ivabradine, the three to five watery stools a day, result- Medical Center, Brooklyn, NY and researchers point out, the statisti- ing in a weight loss of 3 kg. A colonos- Université de Montréal, Montréal, cal estimates of differences between copy had been performed at the onset Canada analyzed data from eight the patients with and without DM of his symptoms, which revealed no multicenter, randomized, double- were less precise for those drugs. pathology. Thus, he was presumed to blind, controlled trials. Six of the trials Nevertheless, the efficacy results for have irritable bowel syndrome. At the enrolled patients with chronic stable atenolol and amlodipine were com- current evaluation, he reported taking angina pectoris and documented CAD, parable to those found for ivabradine. no regular medications and having one enrolled patients who had docu- The researchers noted no special no family history of endocrinopathy mented CAD and had been treated safety concerns for patients with or cancer. for congestive heart failure, and one diabetes taking ivabradine. These Results of physical examination, enrolled patients with documented patients, for instance, did not have lower gastrointestinal endoscopy, and CAD with or without angina. Three higher rates of sinus bradycardia or serial biopsies were unremarkable. studies compared ivabradine to pla- visual disturbances—both of which Upper gastrointestinal endoscopy cebo, three compared the drug to are known to be related to the action revealed low-grade esophagitis, dif- atenolol, one compared it to amlodi- of ivabradine. Neither was ivabra- fuse gastritis, and multiple superfi- pine, and one compared two ivabradine dine associated with adverse effects cial postbulbar ulcers. The gastric pH doses to one another. Collectively, the on glucose metabolism. Given that was lower than 2. Histology indicated trials involved 3,079 patients without beta-blocker therapy can reduce both Helicobacter pylori–negative hyper- diabetes (2,372 who received ivabra- insulin secretion and sensitivity to plastic gastritis. Duodenal biopsies, dine, 352 who received atenolol, and insulin and may raise blood glu- however, revealed villous atrophy and 355 who received amlodipine) and cose and hemoglobin A1c levels, the crypt hyperplasia. His fasting gastrin 667 with diabetes (535 who received researchers conclude that “ivabradine level was 217 pg/mL (reference value, ivabradine, 83 who received atenolol, represents an attractive alternative to less than 150 pg/mL). and 49 who received amlodipine). beta-blockers in patients with stable After the patient started PPI ther- The researchers found no obvious angina and DM.” apy at double the standard dose, his differences in the absorption, metabo- Source: Am J Cardiol. 2010;105(1):29–35. diarrhea ceased completely for the lism, and excretion of ivabradine in doi:10.1016/j.amjcard.2009.08.642. first time in three years. This out- FEDERAL PRACTITIONER • FEBRUARY 2010 E2 DRUG MONITOR ONLINE EDITION come, in conjunction with the endo- coduodenectomy and liver metastasis PPIs may delay early diagnosis by scopic findings, supported a clinical resection. After radical surgical resec- controlling symptoms and by physi- diagnosis of ZES despite ambiguous tion, he remained tumor free during a ologically increasing gastrin levels. gastrin levels. six-year follow-up. Conversely, however, “clinicians After the PPI was withdrawn, Clinical diagnosis of ZES is dif- should appreciate that any unex- another two serum gastrin measure- ficult, the authors say, because it pre- plained chronic diarrhea disappearing ments yielded normal results (124 sents through signs and symptoms under PPI therapy is strongly sugges- and 147 pg/mL), and subsequent of the most prevalent gastrointestinal tive for ZES and that an appropriate secretin simulation tests failed to find disorders, such as gastroesophageal diagnostic evaluation is warranted in excessive gastrin production. Results reflux and chronic diarrhea. The latter such situations,” say researchers. ● of endoscopic ultrasound were sug- is often the most prominent symptom, Source: Am J Med. 2009;122(11):e9–e10. gestive of a duodenal wall gastrinoma as excessive gastric acid causes high doi:10.1016/j.amjmed.2009.06.018. and showed an isolated liver metasta- intestinal volume loads and mucosal sis. The patient underwent pancreati- injury. FEDERAL PRACTITIONER • FEBRUARY 2010 E3.