Early ARNI treatment initiation after acute decompensated HF well tolerated in HFrEF patients with CKD

Initiation of sacubitril/valsartan in patients with renal impairment early after acute decompensated heart failure in the TRANSITION study

Presented at the ESC HF 2021 by Ewa Straburzynska-Migaj (Poznan, Poland)

Introduction and methods

Many patients with HF also have CKD. These patients have a higher risk of adverse outcomes during the vulnerable phase after acute decompensated HF episodes and up-titration of HF treatment can be challenging.

The TRANSITION study was an open-label, randomized study that compared early initiation and up-titration of sacubitril/valsartan treatment with post-discharge initiation of sacubitril/valsartan after acute decompensated HF in stabilized patients with HFrEF. This post hoc analysis of TRANSITION assessed the up-titration success and tolerability of early initiation of sacubitril/valsartan in patients with HFrEF with or without CKD (CKD group n=476; non-CKD group n=483). The primary endpoint was achieving target dose of sacubitril/valsartan (97/103 mg) twice daily at 10 weeks post-randomization. CKD was defined as eGFR of ≥30 to <60 mL/min/1.73m².

Results

• Early initiation and up-titration of sacubitril/valsartan to the 97/103 mg target dose was achieved in 42% of patients with CKD and in 54% of patients without CKD (P<0.001).

• 58% Of patients with CKD achieved and maintained a sacubitril/valsartan dose of 49/51mg and or 97/103 mg for at least 2 weeks leading to week 10 vs. 73% of patients without CKD (P<0.001).

• The majority of patients achieved and maintained sacubitril/valsartan treatment at any dose for at least 2 weeks leading to week 10 (84% with CKD vs. 92% without CKD, P<0.001).

• There was a smaller reduction in NT-proBNP and hs-TnT levels in patients with CKD compared to those without CKD (P<0.001 for both biomarkers).

• Also, all-cause or first HF related re-hospitalization events after 182 days were higher in the CKD group than in the non-CKD group (all-cause re-hospitalization P=0.0026; HF hospitalization P=0.0019).

• 9.1% Of patients in the CKD group discontinued sacubitril/valsartan therapy due to adverse events compared to 2.5% in the non-CKD group (P<0.001). The CKD group experienced more hyperkalemia (P<0.001), cardiac failure (P=0.029), and renal impairment (P=0.002).

Conclusion

This post hoc analysis of the TRANSITION study showed that early initiation and up-titration of sacubitril/valsartan after decompensated HF was well tolerated in patients with CKD. However, patients with CKD were more susceptible to hyperkalemia and renal impairment and may require slower up-titration during the vulnerable post-discharge phase.

–Our coverage of ESC HF 2021 is based on the information provided during the congress –