Prevent the first cirrhotic decompensation: why prefer carvedilol

A vast retrospective study confirms the superiority of carvedilol over other non-cardio-selective beta to prevent. Therefore, cirrhosis decompensations. Similarly, New combined strategies are opening up to patients.

Cirrhosis represents a major global health burden, causing 4 % of all deaths worldwide in 2023 (1). Moreover, The latest Baveno VII conference (2) has taken stock of the use of non-cardio-selective beta (BBNCS) in this pathology. Moreover, These drugs are indicated in patients with clinically significant portal hypertension (HTPCS) in order to prevent the first decompensation.

HTPCS is defined by: a Porto-Cave gradient ≥ 10 mmHg. Therefore, or an ascite only radiological, or eeso-gastric varicose veins (independently of their size, child score, red signs or port-systic derivations), or hepatic elasticity ≥ 25 kpa. Therefore,

The anticipate study suggested that the BBNCs could be prescribed more widely without systematic recourse to endoscopy. Furthermore, based on elastometric criteria and prevent first cirrhotic decompensation: why a low -level platelet rate to establish a high probability of HTPCS. However, this approach includes a risk of surprisingness of up to 40 %. For example, Regarding the choice between the different beta-blockers molecules. Furthermore, no major study has made it possible to decide since the Predesci study (3). Moreover, The latter. Therefore, which included a high proportion of viral hepatitis, had demonstrated the superiority of the carvedilol (33 patients) over propranolol (67 patients) to prevent decompensation, mainly ascitic. Therefore,

A major retrospective study

A new study (4) assessed the effect of carvedilol compared to propranolol/Nadolol on the occurrence. In addition, of liver decompensations in patients with offset cirrhosis. Therefore, This retrospective analysis used Trinetx, a national database bringing together anonymized electronic medical records of more than 110 million patients. The study included adults (≥ 21 years) with compensated cirrhosis having received at least a prescription from Carvedilol. Nadolol prevent first cirrhotic decompensation: why or Propranolol after their diagnosis of cirrhosis, between January 2000 and June 2019. Patients with history of liver decompensation prior to the initiation of BBNCS were excluded. A pairing by propensity score on 35 covariables (demographic data. physical measures, biological values, treatments and comorbidities) made it possible to build groups of 7,795 patients. A target test emulation was carried out with liver decompensation as a main evaluation criterion.

The use of carvedilol has been associated with a significant reduction in the risk of liver decompensation (risk ratio [HR] 0.64) Compared to Propranolol/Nadolol. The most important reductions were observed for: Varicose bleeding (HR 0.27), hepatic encephalopathy (HR 0.62), ascites (HR 0.62). Additionally, The superiority of the carvedilol was confirmed both in the face of Nadolol (HR 0.60) and propranolol (HR 0.68). These results have proven to be coherents according to sex. ethnic groups (with the exception of Asian patients), as well prevent first cirrhotic decompensation: why as between the different etiologies of cirrhosis: viral hepatitis B and C, hepatic diseases linked to alcohol, masld and other causes.

Like any retrospective cohort study. this analysis has inherent limits: risk of residual confusion despite the matching on 35 covariables, use of diagnostic coding, and absence of detailed clinical data (dosage, port-cave gradient, other antihypertensive).

Concordance with previous hemodynamic studies

These results agree with those of Fortaa et al. (5) and remain consistent in the analysis of the subgroups. These authors also brought in a better hemodynamic response with carvedilol than with other BBNCs for a median follow. -up of 36.3 months, although their study is limited by a sample of 256 patients. In the study of Fortaa et al.. The effectiveness of carvedilol in women did not reach statistical significance despite a favorable HR, probably due to the small size of the female sample (n = 86).

This broader cohort prevent first cirrhotic decompensation: why in real conditions (6. 188 women) confirms a comparable and significant efficiency between the sexes thanks to its widest representation.

A recent network meta-analysis (6) has confirmed the superiority of the carvedilol in terms of mortality all causes in. patients with eso-gastric varices (RR: 0.32 [IC à 95 % : 0,17-0,57]), ahead of Nadolol (RR: 0.48) and Propranolol (RR: 0.77). Similar results have been observed for mortality linked to the liver. Carvedilol has also classified as the safest BBNCS in terms of undesirable effects.

In practice: initiate. monitor treatment

An electrocardiogram and cardiological opinion must systematically be requested before the initiation of Carvedilol, which is also better tolerated when cirrhosis is offset.

The initial dosages are:

• Carvedilol: ½ tablet of 6.25 mg morning. evening (maximum dose: 25 mg/d);
• Propranolol: 40 mg morning and evening (maximum dose: 160 mg lp/d);
• Nadolol: Use outside AMM in France.

The doses are gradually increased over a period of 3 prevent first cirrhotic decompensation: why weeks depending on clinical tolerance.

The optimal hemodynamic objective is a decrease of at least 10 % of the initial port-cave gradient or obtaining a gradient ≤ 12 mmHg. In clinical practice. the objectives are: reduction in heart rate by 25 % or obtaining a pulse close to 55 beats/min, maintenance of a systolic blood pressure ≥ 90 mmHg.

BBNC dosage should be reduced in patients with ascites. The treatment should be interrupted if the systolic blood pressure is less than 90 mmHg, the average blood pressure <65 mmHg, and/or in the event of hepato-renal syndrome.

In decompensated patients (ascites and/or hemorrhage). Furthermore, the establishment of a transjugular port-system shunt (TIPS) and the indication of liver transplantation should be discussed.

Two promising associations for patients at high risk hemorrhagic

Carvedilol has an anti-α1-Adrenergic activity which makes it more effective. than other BBNCs to reduce portal pressure. However, 35 to 45 % of prevent first cirrhotic decompensation: why patients still have an insufficient hemodynamic response. In 82 patients with severe portal hypertension. sub-optimal response to propranolol, the Carvedilol + Simvastatin association (7) significantly improves the reduction in portal pressure, endothelial dysfunction and pro-inflammatory cytokines compared to monotherapy.

For primary prophylaxis in 330 CHILD BC patients with high -risk varicose veins. the Carvedilol + Endoscopic ligature association is superior to isolated treatments to prevent varicose bleeding (8).

In conclusion, this vast study confirms the superiority of the carvedilol over propranolol and nadolol in the offset cirrhosis. Therapeutic associations (Carvedilol + Simvastatin or + Endoscopic ligature) are opening up new perspectives for high -risk hemorrhagic patients. Future studies including detailed hemodynamic data (Porto-Cave gradient, tensioning targets) remain necessary to optimize therapeutic strategies.