No Increased Risk of Hyperkalemia for Patients Treated With Sacubitril/Valsartan

Results of previous studies have shown that sacubitril/valsartan, a new class of angiotensin receptor neprilysin inhibitor, is beneficial for patients with heart failure via blocking the degradation of natriuretic peptides and inhibition of activation of the renin-angiotensin-aldosterone system (RAAS). Those effects also relate to the pathophysiologic mechanisms of chronic kidney disease (CKD); however, according to Wei Zhou, MD, and Xinyue Yang, MD, and colleagues, the effects on CKD are unclear.

The researchers performed a systematic review and meta-analysis to examine the efficacy and safety of sacubitril/valsartan for patients with CKD. Results were reported online in International Urology and Nephrology [doi.org/10.1007/s11255-023-03599-w].

The search included Embase, PubMed, and the Cochrane Library. Studies of interest were randomized controlled trials comparing sacubitril/valsartan with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBS) in patients with CKD with estimated glomerular filtration rates (eGFR) below 60 mL/min/1.73 m². Effect size was estimated using the odds ratio (OR) with 95% CI.

The meta-analysis included six trials with a total of 6217 patients with CKD. Sacubitril/valsartan attenuated the risk of cardiovascular death or hospitalization for heart failure (OR, 0.68; 95% CI, 0.61-0.76; P<.00001), and prevented the incidence of serum creatinine elevation in patients with CKD (OR, 0.79; 95% CI, 0.67-0.95; P=.01).

Results of subgroup analysis of eGFR demonstrated that with long follow-up, sacubitril/valsartan significantly decreased the number of patients with more than 50% reduction in eGFR compared with ACEi/ARBs (OR, 0.52; 95% CI, 0.32-0.84; P=.008). In patients with CKD, sacubitril/valsartan reduced the incidence of end-stage renal disease (OR, 0.59; 95% CI, 0.29-1.20; P=.14).

In analyses of safety, there was an association between sacubitril/valsartan and the occurrence of hypotension (OR, 1.71; 95% CI, 1.15-2.56; P=.008). There was no trend toward increasing the risk of hyperkalemia in patients in the sacubitril/valsartan group (OR, 1.09; 95% CI, 0.75-1.60; P=.64).

In conclusion, the authors said, “This meta-analysis indicated that sacubitril/valsartan improved renal function and conferred effective cardiovascular benefits in patients with CKD, without serious safety issues being observed. Thus, sacubitril/valsartan may be a promising option for patients with CKD. Certainly, further large-scale randomized controlled trials are needed to confirm these conclusions.”