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Entresto in HF Tied to Less Kidney Decline

— Meta-analysis shows trend favoring drug over ACE inhibitor or ARB alone

MedpageToday

In heart failure patients, combination sacubitril/valsartan (Entresto) appeared to be more protective of kidney functioning versus either an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) alone, a new study found.

The systematic review and meta-analysis of four randomized controlled trials showed a trend toward less renal impairment for patients on sacubitril/valsartan compared to those on enalapril or valsartan alone (risk ratio [RR] 0.75, 95% CI 0.55-1.02, I2= 53%, P=0.06), reported Eloisa Trina Generoso, MD, of St. Luke's Medical Center in the Philippines.

Heart failure patients on sacubitril/valsartan did see a significantly lower risk for a rise in serum potassium level versus those on enalapril or valsartan alone (RR 0.90, 95% CI 0.84-0.96, I2= 66%, P=0.001). This is of note, as ACE inhibitors in patients with chronic kidney disease may cause hyperkalemia.

And treatment with sacubitril/valsartan was also tied to a reduced risk for a rise in serum creatine level than enalapril or valsartan alone (RR 0.86, 95% CI 0.78-0.95, I2= 72%, P=0.002), according to the presented at the National Kidney Foundation's virtual Spring Clinical Meeting.

"Sacubitril-valsartan may be an attractive and safe therapy for patients who are suffering from chronic kidney disease alongside heart failure," Generoso told 鶹ý.

She continued, stating that she was rather surprised to see these findings, explaining that despite the efficacy of ACE inhibitors or ARBs for patients with heart failure and chronic kidney disease, they've been linked to some renal risk.

"We did not expect to find that 'two wrongs' would actually make a 'right' -- in this case, reduction of risks for impairment of kidney function," she said. "Previous studies have shown that use of RAS [renin-angiotensin-system] agents in heart failure can harm the kidneys, while neprilysin inhibitors had their share of safety concerns."

But since sacubitril/valsartan became "one of the 'wonder drugs of this decade' -- being tested for almost every heart failure patient," Generoso said her group was particularly interested to determine its effects on the kidneys, as heart failure commonly involves impairment of other organs.

Among the four sacubitril/valsartan trials, which included roughly 14,300 participants in total, two studies included the ACE inhibitor enalapril (PARADIGM-HF, PIONEER-HF) and two used the ARB valsartan (, PARAGON-HF) as comparators.

Currently, suggests patients with severe renal impairment should start this treatment taking only half the recommended starting dosage.

Generoso suggested that additional randomized controlled trials, with larger sample sizes and longer-term follow-up, looking at sacubitril-valsartan's effect on kidney function are warranted.

  • author['full_name']

    Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

Study authors reported no relevant disclosures.

Primary Source

National Kidney Foundation

Generoso ETC, et al "Renal outcomes of sacubitril-valsartan versus ACE inhibitors and angiotensin receptor blockers in heart failure: A systematic review and meta-analysis" NKF 2020; Abstract 198.