Bleeding Disorder, A Newly Recognized Adverse Event Following Sacubitril/Valsartan Therapy

Sacubitril/valsartan (Entresto) is the only currently approved angiotensin receptor-neprilysin inhibitor (ARNI) drug. It demonstrates important therapeutic outcomes in heart failure patients by reducing hospitalizations and deaths. ARNI is generally safe but concerns about adverse drug reactions (ADRs) exist. This report documents a potential bleeding disorder, evidenced by elevated prothrombin time (PT) and international normalized ratio (INR), as a newly identified ADR.

Despite not receiving anticoagulant medication, three male heart failure patients had elevated PT/INR values within 14 days to four months of initiating Entresto 50 mg twice daily. Temporary discontinuation (dechallenging) of Entresto resulted in a decline in PT/INR, while it increased upon re-challenge in at least one patient. Laboratory findings showed varying degrees of anaemia, occasional renal and hepatic abnormalities, with normal platelet counts. Naranjo scores (6-8) support a probable causal relationship between Entresto and the bleeding tendency, warranting careful coagulation monitoring during treatment.

This case series explicitly identified a probable causal relationship between Entresto (ARNI) and a potential bleeding risk as evaluated by the Naranjo ADR probability scale. By highlighting this previously unidentified ADR, this report attempts to raise awareness among healthcare practitioners regarding the need for vigilant monitoring of coagulation parameters in high-risk patients, even without concomitant anticoagulant treatment.

To our knowledge, this case series is the first report in the medical literature to specifically recognize a probable causal relationship between angiotensin receptor-neprilysin inhibitor treatment and a potential bleeding risk as evaluated by the Naranjo adverse drug reaction probability scale.Healthcare practitioners are urged to vigilantly monitor coagulation parameters in high-risk patients, even in the absence of concomitant anticoagulant treatment.