The meta-analysis of propranolol compared with endoscopic variceal ligation for primary prophylaxis of variceal bleeding by Imperiale and Chalasani 1 favors pharmacotherapy despite the fact that "none of the trials measured the hemodynamic response to propranolol." "Blind beta blockade" is the administration of beta adrenergic blocking drugs for prevention of variceal hemorrhage to the surrogate end points of pulse and blood pressure. 2 These surrogate end points should be abandoned because they achieve the desired protective hemodynamic response in only one third of patients. [3][4][5] Consequently only one third of patients receiving propranolol were in fact "treated patients." In contrast all banded patients received the intended therapy. Failure to achieve a protective hemodynamic response in two thirds of the patients treated with propranolol produces a significant negative bias that minimizes the reported advantage of propranolol over banding.
A reduction in portal-hepatic pressure gradient of 20% is required to confer protection from variceal bleeding. 3-5 A portal-hepatic gradient less than 12 mm Hg yields nearly complete protection from recurrent bleeding. [3][4][5] The gradient as measured by hepatic vein catheterization is a minimum risk ambulatory technique requiring only local anesthesia.
Beyond propranolol or other beta blocking drugs, many other drugs are effective in lowering portal pressure. Adding isosorbide-5-mononitrate to beta block for prevention of variceal rebleeding increases the desired hemodynamic response to 53% of patients. 6,7 Albillos et al. showed that combined alpha and beta blockade further increases the response rate to 85%. 8 An improved hemodynamic response gives the anticipated reduction in bleeding. [3][4][5][6][7][8] A nonselective beta-blocker with anti-adrenergic activity is another option. 9 Presumably adding a diuretic would further improve the effectiveness of pharmacotherapy because the portal pressure set point responds independently to changes in blood volume or blood flow. [10][11][12] A strategy of hemodynamic monitoring and adding pharmacotherapy as necessary would tilt a comparison of pharmacotherapy versus banding even more strongly in favor of pharmacotherapy. Blind beta blockade omits the documented individual variation in response of cirrhotic patients with portal hypertension to drug therapy. [13][14][15] Separating prophylactic from therapeutic therapy of variceal hemorrhage in high-risk patients may have heuristic virtue, but it is clinically dubious when the risk of bleeding is 30% with a mortality of 10% to 15%. The need for hemodynamic monitoring of pharmacotherapy should not be ignored and must be considered in future investigations and meta-analyses. "When you cannot measure it, when you cannot express it in numbers, you have scarcely, in your thoughts advanced to the stage of Science,