“Early Use of TIPS in Patients with Cirrhosis and Variceal Bleeding”
N Engl J Med. 2010 Jun 24;362(25):2370-9. [free full text]
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Variceal bleeding is a major cause of morbidity and mortality in decompensated cirrhosis. The standard of care for an acute variceal bleed includes a combination of vasoactive drugs, prophylactic antibiotics, and endoscopic techniques (e.g. banding). Transjugular intrahepatic portosystemic shunt (TIPS) can be used to treat refractory bleeding. This 2010 trial sought to determine the utility of early TIPS during the initial bleed in high-risk patients, when compared to standard therapy.
Population: cirrhotic patients with acute esophageal variceal bleeding, either Child-Pugh class C with score 10-13 or class B (score 7-9) with active bleeding at diagnostic endoscopy
Notable exclusion criteria: Child-Pugh score > 13, age > 75, HCC that did not meet transplantation criteria, bleeding gastric varices, total portal vein thrombosis, prior TIPS
All patients received endoscopic band ligation (EBL) or endoscopic injection sclerotherapy (EIS) at the time of diagnostic endoscopy. All patients also received vasoactive drugs (terlipressin, somatostatin, or octreotide).
Intervention: TIPS performed within 72 hours after diagnostic endoscopy
Comparison: 1) treatment with vasoactive drugs with transition to nonselective beta blocker when patients free of bleeding followed by 2) addition of isosorbide mononitrate to maximum tolerated dose, and 3) a second session of EBL at 7-14 days after the initial session (repeated q10-14 days until variceal eradication was achieved)
Outcome:
Primary – composite of failure to control acute bleeding or failure to prevent “clinically significant” variceal bleeding (requiring hospital admission or transfusion) at 1 year after enrollment
Secondary, selected
- mortality at 1 year
- failure to control acute bleeding
- early rebleeding (at 5 days and 6 weeks)
- rate of development of hepatic encephalopathy (HE)
- ICU days, time in hospital
Results:
359 patients were screened for inclusion, but ultimately only 63 were randomized. Baseline characteristics were similar among the two groups except that the early TIPS group had a higher rate of patients with previous hepatic encephalopathy. Among early TIPS patients, the mean portal pressure dropped from 20.2±7 mmHg to 6.2±3 mmHg.
The primary composite endpoint of failure to control acute bleeding or rebleeding within 1 year occurred in 14 of 31 (45%) patients in the pharmacotherapy-EBL group and in only 1 of 32 (3%) of the early TIPS group (p = 0.001). The 1-year actuarial probability of remaining free of the primary outcome was 97% in the early TIPS group vs. 50% in the pharmacotherapy-EBL group (ARR 47 percentage points, 95% CI 25-69 percentage points, NNT 2.1).
Regarding mortality, at one year, 12 of 31 (39%) patients in the pharmacotherapy-EBL group had died, while only 4 of 32 (13%) in the early TIPS group had died (p = 0.001, NNT = 4.0).
Regarding HE: the 1-year actuarial probability of HE was 28% in the early TIPS group vs. 40% in the pharmacotherapy-EBL group (p = 0.13). Most of the episodes of HE occurred during the index bleed. Following discharge from index hospitalization, the 1-year risk of additional HE episodes was 10% in the pharmacotherapy-EBL group and 19% in the early TIPS group (p = 0.80).
There were no group differences in 1-year actuarial probability of new or worsening ascites.
There were no group differences in length of ICU stay or hospitalization duration.
Implication/Discussion:
Early TIPS in acute esophageal variceal bleeding, when compared to standard pharmacotherapy and endoscopic band ligation, improved control of index bleeding, reduced recurrent variceal bleeding at 1 year, and reduced all-cause mortality.
Prior studies had demonstrated that TIPS reduced the rebleeding rate but increased the rate of hepatic encephalopathy without improving survival. As such, TIPS had only been recommended as a rescue therapy. Obviously, this study presents compelling data that challenges these paradigms.
The authors note that in “patients with Child-Pugh class C or in class B with active variceal bleeding, failure to initially control the bleeding or early rebleeding contributes to further deterioration in liver function, which in turn worsens the prognosis and may preclude the use of rescue TIPS.”
Authors at UpToDate note that, given the totality of evidence to date, the benefit of early TIPS in preventing rebleeding “is offset by its failure to consistently improve survival and increasing morbidity due to the development of liver failure and encephalopathy.” Today, TIPS remains primarily a salvage therapy for use in cases of recurrent bleeding despite standard pharmacotherapy and EBL. There may be a subset of patients in whom early TIPS is the ideal strategy, but further trials will be required to identify this subset.
Further Reading/References:
1. Wiki Journal Club
2. 2 Minute Medicine
3. UpToDate, “Prevention of recurrent variceal hemorrhage in patients with cirrhosis”
Summary by Duncan F. Moore, MD