Nonselective beta-blockers, a standard therapy for preventing esophageal variceal bleeding in patients with portal hypertension, may also reduce mortality in those with gastric varices.
Gastric varices, a complication of portal hypertension, are less common than esophageal varices but are associated with higher rates of severe bleeding and mortality. Gastric variceal hemorrhage carries a particularly poor prognosis, with mortality rates approaching 45% within 3 years and rebleeding rates as high as 35% to 90% despite intervention.
Unlike esophageal varices, standardized treatment guidelines for gastric varices remain sparse. Existing approaches including endoscopic band ligation, cyanoacrylate injection, balloon-occluded retrograde transvenous obliteration, and portosystemic shunting are often limited by recurrent bleeding and procedure-related risks, according to Rebecca H. Moon, MD, of the Department of Gastroenterology, Kaiser Permanente Los Angeles Medical Center, and colleagues.
Nonselective beta-blockers (NSBBs) reduce portal hypertension through combined beta-1 and beta-2 blockade, lowering cardiac output and inducing splanchnic vasoconstriction, which decreases portal venous inflow by up to 35%. Additional protective effects, such as reducing bacterial translocation and lowering the incidence of spontaneous bacterial peritonitis, have also been noted. Three primary NSBBs are used clinically: propranolol, nadolol, and carvedilol. While carvedilol exerts a stronger effect by adding alpha-1 blockade, it carries higher risks of hypotension and renal dysfunction in patients with advanced cirrhosis.
Dr. Moon and fellow investigators analyzed data from Kaiser Permanente Southern California, identifying adults aged 18–75 years who were newly diagnosed with gastric varices between 2015 and 2021. Patients with prior splenectomy, transjugular intrahepatic portosystemic shunt (TIPS) procedures, multiple NSBB exposures, or insufficient follow-up were excluded. Participants were followed through February 2022.
The primary outcomes included gastric variceal hemorrhage, esophageal variceal hemorrhage, TIPS placement, liver transplantation, and overall mortality.
The study included 1,276 patients (63% male; mean age, 58.4 years). Nearly half (48%) were Hispanic and 39% White. According to the Sarin Classification, the most common variceal types were GOV1 (29.8%), GOV2 (26.3%), and IGV1 (36.8%).
Comorbidities were frequent, including hypertension (65.9%), obesity (48.5%), and type 2 diabetes (44.7%). More than half of patients had esophageal varices, and 38% had ascites. Major etiologies of liver disease included alcohol use disorder (33%), hepatitis C (21%), and hepatitis B (3%).
During a median follow-up of 1.1 years, 7.1% developed gastric variceal hemorrhage, 21.7% experienced esophageal variceal hemorrhage, 4% required TIPS, 5.3% underwent liver transplantation, and overall mortality was 40%.
Of the 1,276 patients, 767 (62.5%) received NSBB therapy. After adjusting for demographics and comorbidities, NSBB use was significantly associated with lower mortality compared with nonuse (39.2% vs 50.9%; odds ratio [OR] = 0.62; 95% confidence interval [CI] = 0.46–0.84).
No significant differences were observed in rates of gastric variceal hemorrhage, esophageal variceal hemorrhage, TIPS placement, or liver transplantation between users and nonusers. Nadolol was most strongly associated with survival benefit (OR = 0.55), followed by propranolol (OR = 0.71). Outcomes for carvedilol could not be assessed due to small sample size. Median survival from NSBB initiation was 1.4 years.
The authors suggested that the survival benefit of NSBBs in gastric varices may not be mediated solely through bleeding reduction but could also reflect broader protective effects, similar to results seen in the PREDESCI trial, where NSBBs prevented cirrhosis decompensation rather than directly reducing variceal hemorrhage.
The study found higher rates of variceal hemorrhage among Hispanic patients, raising questions about genetic predisposition, metabolic syndrome prevalence, or socioeconomic factors as potential contributors. The authors emphasized the need for further research to explore these disparities.
As a retrospective cohort study, causality cannot be confirmed. Uneven subgroup distribution, underrepresentation of carvedilol, and modest follow-up duration also limit definitive conclusions.
Further prospective studies are needed to clarify the effects of NSBBs on gastric varices and to refine treatment strategies for this high-risk population. Given the high mortality associated with gastric variceal hemorrhage, ongoing investigation into pharmacologic and interventional approaches remains critical to improving patient outcomes, the investigators concluded.
They reported having no conflicts of interest.
Source: Gastro Hep Advances
