The study found that being prescribed an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) at hospital discharge was associated with a “significant modest” 14% reduction in death from any cause over about 8 years in older patients with systolic HF and CKD.
“The benefits of ACE inhibitors and ARBs in patients with systolic HF are well established,” first author Dr. Ali Ahmed from the University of Alabama at Birmingham told Reuters Health by email. “However, concerns remained about the safety and benefit of these drugs in older HF patients and in HF patients with CKD. The vast majority of HF patients are older adults and also have CKD. Findings from our study suggest ACE inhibitors or ARBs may improve outcomes in older systolic HF patients with mild to moderate CKD,” Dr. Ahmed said.
The study, published online February 9 in the American Journal of Medicine, included 1,665 patients with systolic HF (ejection fraction < 45%) and CKD (eGFR < 60 mL/min); 1,046 (63%) were prescribed an ACE inhibitor (n=866) or ARB (n=180) upon hospital discharge. Seventeen patients received both drugs.
The study team used propensity score matching to assemble a cohort of 444 pairs of patients receiving and not receiving this therapy who were well balanced on 56 baseline characteristics. Of the 888 matched patients, 591 had CKD stage 3B or greater.
During more than 8 years of follow-up, death from any cause occurred in 75% and 79% of matched patients with CKD on therapy and not on therapy, respectively (hazard ratio [HR] 0.86; p=0.045), the authors report. A similar reduction in all-cause mortality was observed in a subgroup of matched patients with eGFR <45 mL/min (HR 0.83; p=0.046)
The apparent protective effect seemed stronger among those patients receiving these drugs at or above target doses, the authors say.
However, Dr. Ahmed told Reuters Health, “It also appears that the effect of these drugs on outcomes in those with CKD may be less robust than in those without CKD.” Among 171 pairs of propensity-matched patients without CKD, renin-angiotensin inhibition was associated with a significant 28% reduction in all-cause mortality (HR 0.72; p=0.015) and heart failure hospitalization (HR 0.71; p=0.023).
In a telephone interview with Reuters Health, Dr. Robert A. Phillips, of the University of Massachusetts in Worcester, who was not involved in the study, called it “important.”
“Specialists as well as primary care physicians are very wary about using renin-angiotensin system blockers, either ACE inhibitors or angiotensin receptor blockers, when there is a decrease in GFR,” he explained. “But it is those patients in particular who benefit. We showed that in the African American study of kidney disease and hypertension (Arch Intern Med. 2009;169:1587-1594) and in that study there was very little hyperkalemia.”
Dr. Ahmed and colleagues say several factors distinguish their study from prior studies including “its larger sample size, longer follow-up, use of a more rigorous methodology, inclusion of both ACE inhibitors and ARBs, and use of contemporary therapy for systolic HF.”
Nonetheless, Dr. Phillips noted, “It wasn’t a randomized study so there could be some confounding by bias. Also, they didn’t follow intermediate end points so they don’t know about the incidence of hyperkalemia or adverse events, but for the hard end point of mortality it looks like treatment was beneficial in patients with heart failure and reduced ejection fraction and an eGFR that was pretty low. You still have to be careful about monitoring these patients when you put them on renin-angiotensin system blockade, but that doesn’t mean they should be denied this therapy,” he added.
Dr. Ahmed added: “As in all HF patients, these drugs should not be prescribed to those with a history of prior allergic reaction or adverse effect and need to use with caution in those with low systolic blood pressure, high serum potassium levels, and renal failure.”