Upper GI bleed: no clear benefit from adding isosorbide mononitrate to nadolol to patients with oesophageal varices and cirrhosis.

Clinical bottom line (level 2b-)

Patients with cirrhosis and oesophageal varices who took isosorbide mononitrate and nadolol compared with nadolol alone were not clearly less likely to have a variceal bleed.

Merkel et al: The Lancet 1996; 348: 1677-1681

Expires November 2002

The study

Single-blinded ?concealed randomised trial with intention-to-treat
Setting: 9 acute hospitals, Italy

146 patients (aged mean 58, 62% male) with cirrhosis (diagnosed on histology or previous admissions) and oesophageal varices, but no previous variceal bleeding

Excluded if

previous treatment for portal hypertension
Child-Pugh score > 10
any malignancy
unable to attend follow-up
contraindications to beta-blockers (AV block more severe than first-degree heart block, sinus bradycardia with a heart rate < 50 beast/min, arterial hypotension with a systolic pressure < 85 mmHg, heart failure, asthma, peripheral vascular disease or diabetes needing insulin)
long-acting nitrates
concomitant or recent therapy with interferon for hepatitis B or C
aged < 18, > 70

Control Group: (n = 74, 43 analysed): nadolol 40 mg once daily titred to achieve a 20-25% decrease in resting heart rate: maximum dose 160 mg daily, and placebo
Experimental Group: (n = 72, 51 analysed): nadolol 40 mg once daily titred as above, and isosorbide mononitrate 10 mg twice daily, increased to 20 mg twice daily unless hypotension or severe headache occurred.

64% followed for 40 months

The evidence

Outcome	Time to outcome	CER	EER	RRR (95% CI)	ARR (95% CI)	NNT (95% CI)
variceal bleeding	40 months	11 (14.86%)	4 (5.56%)	63% (-12% to 88%)	9.31% (-0.37% to 19.0%)	11 (NNT = 5 to infinity; NNH = 270 to infinity)

Comments

The study is too small to show any difference between the two groups.
Titration of dose of nadolol to beta-blockade may not relate to reduced venous portal pressure

Citation

Merkel C, Marin R, Enzo E, et al: Randomised trial of nadolol alone or with isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. The Lancet 1996; 348: 1677-1681

Search Terms: ?
Contributor: Chris Ball and Musab Hayatli, November 1999
Reviewer: Lawrence Friedman

_{Clinical Question.}

_Patient	_{varices, cirrhosis}
_{Intervention or Exposure}	_{isosorbide mononitrate and beta-blocker}
_Comparison	_beta-blocker
_Outcome	_{death, bleeding}