Early identification of haemodynamic response to pharmacotherapy is essential for primary prophylaxis of variceal bleeding in patients with ‘high‐risk’ varices

Abstract

SUMMARY BackgroundA 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 betablocker and benefits of HVPG-guided 'a la carte' approach remain unclear.

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“…Isosorbide mononitrate in combination with nonselective beta blockers has been shown to have a greater portal pressurereducing effect. 15 However, isosorbide mononitrate should be used cautiously in patients with renal impairment and cirrhosis, specially those with ascites. 16 Martin et al 17 showed that NOS inhibition in cirrhotic rats with ascites by L-NAME for 1 week improved renal sodium and free water excretion by improvement in hemodynamics.…”

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“…Various nitrovasodilators have been tried to cause a therapeutic intrahepatic vasodilation, namely, NCX‐1000; nitroflurbiprofen, an NO‐releasing cyclooxygenase inhibitor; atorvastatin, an high mobility group (HMG) CoA inhibitor causing inhibition of hepatic RhoA/Rho‐kinase signaling and activating eNOS in cirrhotic rats. Isosorbide mononitrate in combination with nonselective beta blockers has been shown to have a greater portal pressure‐reducing effect . However, isosorbide mononitrate should be used cautiously in patients with renal impairment and cirrhosis, specially those with ascites .…”

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“…Further difficulties include non-compliance or inadequate dosing. The identification of non-responders by performing baseline and repeat HVPG measurements after 1–3 months of NSBB reatment is an attractive approach, although there is conflicting evidence regarding the efficacy of alternative treatments in non-responders to NSBBs 24 31. The addition of nitrates has been shown to increase the HVPG response to NSBBs, but this only translates to clinical efficacy in preventing rebleeding, not primary prophylaxis 32 33…”