Upper GI bleed: isosorbide mononitrate reduced rebleeds and death during sclerotherapy to eradicate varices

Clinical bottom line (level 1b)

  1. Patients with a recent bleed from oesophageal varices who took isosorbide mononitrate during sclerotherapy to eradiacate varices were less likely to rebleed than patients on placebo (NNT = 4 at 10 weeks)
  2. Patients on isosorbide mononitrate had a lower mortality rate (NNT = 6 at 10 weeks)
  3. There was no clear increase in the number of patients with headaches.
Bertoni et al: Scandinavian Journal of Gastroenterology 1994; 29: 363-370
Expires October 2002

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 5 acute hospitals, Italy

76 patients (aged 18 to 81, mean 62, 70% male) with cirrhosis and a current or recent variceal bleed

Excluded if
  • previous sclerotherapy
  • intractable ascites
  • imminent hepatic transplantation
  • uncontrolled haemorrhage
  • prolonged severe encephalopathy
  • presumed poor compliance with treatment protocol
  • advanced hepatic or extrahepatic malignant tumour
  • resumption of beta-blocker therapy

Note:
  • All patients had endoscopy within 24 hours of admission. The initial haemorrhage was treated with emergency sclerotherapy and somotastatin or terlipressin. Balloon tamponade was used (for 12 -36 hours) if sclerotherapy failed to control bleeding.
  • Patients were randomised within 10 days of admission, when they were haemodynamically stable and had restarted oral intake.
  • Patients underwent sclerotherapy weekly until varices were eradicated.

Control Group: (n = 39, 39 analysed): placebo
Experimental Group: (n = 37, 37 analysed): isosorbide mononitrate slow-release 50 mg po daily until varices were eradicated.
All patients received ranitidine, antacids and vitamin K until variceal eradication, and blood transfusions, diuretics, lactulose and non-absorbable antibiotics as required.
100% followed for 10 weeks range 3 weeks to 25 weeks

The evidence

Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
rebleeding 10 weeks 15
(38.46%)		 4
(10.81%)		 72%
(23% to 90%)		 27.65%
(9.40% to 45.91%)		 4
(2 to 11)
death 10 weeks 9
(23.08%)		 2
(5.41%)		 77%
(-1% to 95%)		 17.67%
(2.57% to 32.77%)		 6
(3 to 39)
headache weeks 5
(12.8%)		 7
(18.9%)		 -48%
(-324% to 49%)		 -6.10%
(-22.5% to 10.3%)		 -16
(NNT = 10 to infinity;
NNH = 4 to infinity)

Comments

  1. There was no significant difference between the 2 groups in the number of sessions required to eradicate varices (mean of 4; range 2 to 10).
  2. In clinical practice, one begins with beta blockers. If a reduction of portal pressure gradient (hepatic vein pressure gradient or HVPG) >20% or below 12 mmHg is not achieved, isosorbide mononitrate may be added.

Citation

  1. Bertoni G, Sassatelli R, Fornaciari G, et al: Oral isosorbide-5-mononitrate reduces the rebleeding rate during the course of injection sclerotherapy for esophageal varices. Scandinavian Journal of Gastroenterology 1994; 29: 363-370
Contributor: Chris Ball and Musab Hayatli, October 1999
Reviewer: Horand Meier

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Outcome