title: Early identification of haemodynamic response to pharmacotherapy is essential for primary prophylaxis of variceal bleeding in patients with 'high-risk' varices.
abstract: BACKGROUND
  A beta-blocker is recommended for primary prophylaxis of variceal bleeding; however, only one-third have hepatic venous pressure gradient (HVPG) response. The role of addition of isosorbide-5-mononitrate (ISMN) to beta-blocker and benefits of HVPG-guided 'a la carte' approach remain unclear.
  
  
  OBJECTIVE
  To determine the benefits of HVPG-guided pharmacotherapy in primary prophylaxis of variceal bleeding using beta-blocker and ISMN.
  
  
  METHODS
  Consecutive patients of cirrhosis, with high-risk varices, with no previous variceal bleeding were included. After baseline HVPG, patients received incremental propranolol to achieve HR of 55/min. After one-month, HVPG was repeated to determine response (<12 mmHg or >or=20% reduction). ISMN was added in nonresponders and HVPG repeated. Patients were followed up for 24 months.
  
  
  RESULTS
  Of 56 patients (age 47 +/- 13, males 79%) from 89 eligible patients, 21 (38%) responded to beta-blocker alone. Six additional patients responded to combination. Thus, overall 48% (27/56) patients responded. Variceal bleeding occurred in seven of 56 (13%) patients [one of 27 (4%) responder, five of 23 (22%) nonresponders and one of six (17%) with unknown response; P = N.S.]. The actuarial probability of variceal bleeding at median 24 months was 4% in responders and 22% in nonresponders (P < 0.05). Ten (18%) patients developed adverse effects to propranolol and six of 35 (17%) to nitrates requiring dose reduction. Risk factors of variceal bleed were grade IV varices and haemodynamic nonresponse.
  
  
  CONCLUSIONS
  For primary prophylaxis, a beta-blocker is effective in 38% and addition of ISMN raises the response rate to about half of patients. The HVPG-guided 'a la carte' approach may be considered for these patients.
authors.affiliation: Department of Gastroenterology, GB Pant Hospital, New Delhi, India.
authors.forename: P
authors.initials: P
authors.lastname: Sharma
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: B C
authors.initials: BC
authors.lastname: Sharma
authors.forename: S K
authors.initials: SK
authors.lastname: Sarin
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004932:Esophageal and Gastric Varices / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000008:administration & dosage; D012307:Risk Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D014665:Vasodilator Agents; D011433:Propranolol; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate