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

ESC HF 2021 This post hoc analysis of the TRANSITION study demonstrated that early initiation and up-titration of sacubitril/valsartan after acute decompensated HF was well tolerated in HFrEF patients with CKD.

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 –