Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Ursodiol was safe and improved lithotripsy success and recurrence rates

ACP J Club. 1991 May-June;114:78. doi:10.7326/ACPJC-1991-114-3-078


Source Citation

Schoenfield LJ, Berci G, Carnovale RL, et al. The effect of ursodiol on the efficacy and safety of extracorporeal shock-wave lithotripsy of gallstones. The Dornier National Biliary Lithotripsy Study. N Engl J Med. 1990;323:1239-45.


Abstract

Objective

To determine the efficacy and safety of lithotripsy alone compared with lithotripsy plus ursodiol treatment for symptomatic patients with gallstones.

Design

Randomized controlled trial of 6 months' duration.

Setting

10 centers in the United States.

Patients

Patients were included if they had biliary pain; were in American Society of Anesthesiologists Class I, II, or III; had ≤ 3 radiolucent stones 5 to 30 mm in diameter; had a nidus of calcification < 3 mm; had had oral cholecystography for visualization of the gallbladder and could receive shock waves that would avoid lungs, bone, aneurysms, or cysts. Patients were excluded if they were pregnant or were in American Society of Anesthesiologists Class IV or V or had a pacemaker; arrhythmia; allergy to contrast medium; coagulopathy; a ductal stone or obstruction; acute cholecystitis, cholangitis, or pancreatitis; a pigment stone; hemolysis; or cirrhosis. Of the 600 patients who were randomly assigned, 511 (85%) completed the study.

Intervention

All patients received extracorporeal shock-wave lithotripsy. In addition, patients were randomized in a double-blind fashion to receive ursodiol (10 to 12 mg/kg of body weight daily; n = 296) or placebo (n = 304), starting 1 week before lithotripsy.

Main outcome measures

Complete disappearance of gallstones and the development of severe biliary pain, acute cholecystitis, or acute pancreatitis.

Main results

At 6 months, among all 600 patients, 61 of the 296 patients (21%) receiving ursodiol were stone free compared with 28 of the 304 patients (9%) receiving placebo (P < 0.001). {This absolute risk improvement of 12% means that 9 patients would need to be treated with lithotripsy plus ursodiol (rather than lithotripsy plus placebo) in order for 1 additional patient to remain free of stones 95%CI 6 to 17; the relative risk improvement was 124%, CI 48% to 240%}.* Lithotripsy plus ursodiol was more successful than lithotripsy alone for both single and multiple stones (P < 0.001). Patients with single stones or smaller stones were more likely to be stone free at 6 months (P < 0.001). The most frequent nonbiliary adverse events were tender abdominal wall (46% of all patients), nausea (36%), and diarrhea (29%), with only diarrhea occurring more frequently in the ursodiol group 33% vs 25% (P < 0.04). Severe biliary pain occurred in 2% of all patients.

Conclusion

Extracorporeal shock-wave lithotripsy with ursodiol was more effective than, and as safe as, lithotripsy alone in eliminating gallstones in symptomatic patients followed for 6 months.

Sources of funding: Dr. Falk Pharmaceutical Company (ursodiol and placebo tablets) and Dornier Medical Systems (technical and logistical support).

Address for article reprint: Dr. L.J. Schoenfield, Division of Gastroenterology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 7511, Los Angeles, CA 90048, USA.

*Numbers calculated from data in article.


Commentary

This large multicenter study provides valuable information not only about the role of bile salts in the treatment of gallstones by extracorporeal shock-wave lithotripsy, but also about the efficacy of lithotripsy in the United States. The data show that lithotripsy plus ursodiol is more effective than, and as safe as, lithotripsy alone for treatment of symptomatic patients with gallstones. However, the rates of complete gallstone dissolution are low when compared with the 63% rate of complete dissolution at 6 months that was reported in Germany, where the technology was developed (1). The dissolution rates may have been lower because the lithotripsy treatments used lower voltage levels and fewer shock waves or because a combination of urso- and chenodeoxycholate was not used.

The rates also may have been lower because the analysis was done conservatively, on an intention-to-treat basis. Other investigators have also reported lower dissolution rates than those reported in Germany.

The study has several limitations. Fewer than 25% of patients with gallstones meet the eligibility criteria used in this study (2), and the study did not address the risk for gallstone recurrence or the costs associated with prolonged treatment and follow-up. Because of these limitations and the low efficacy, lithotripsy is likely to be valuable for only a small subset of patients with gallstones, especially as laparoscopic cholecystectomy emerges as an alternative treatment.

Eric B. Bass, MD, MPH
Johns Hopkins UniversityBaltimore, Maryland, USA


References

1. Barkun AN, Ponchon T. Extracorporeal biliary lithotripsy: review of experimental studies and a clinical update. Ann Intern Med. 1990;112:126-37.

2. Magnuson TH, Lillemoe KD, Pitt HA. How many Americans will be eligible for biliary lithotripsy? Arch Surg. 1989;124:1195-200.