RAS Inhibitors 'Underused' in Renal Patients After an MI, Says New Research

Deborah Brauser

August 12, 2015

MINNEAPOLIS, MN – Prescribers giving too much importance to estimated glomerular filtration rate (eGFR) may be leading to the underuse of renin-angiotensin-system inhibitors (RASIs) after patients with kidney dysfunction have experienced an acute MI, new research suggests[1].

A cohort study of more than 4000 participants from the TRIUMPH registry[2] showed that having a lower eGFR significantly decreased the rate of RASI prescriptions at discharge, regardless of ejection-fraction (EF) status.

Both severe and moderate chronic kidney disease (CKD) were also linked to less use of RASIs when there was no acute kidney injury (AKI); and mild, moderate, and severe CKD was linked to less use when AKI was present.

The investigators note that these medications have been shown to benefit patients with kidney disease, but "in contrast to this clinical logic, we found that RAS-inhibitor use decreased significantly as CKD stage worsened."

Lead author Dr James B Wetmore (Hennepin County Medical Center, Minneapolis, MN) told heartwire from Medscape that renal function "was accorded disproportionate weight" over EF status when it came to therapy decisions. "And it may be deterring some providers from administering RAS inhibitors when they may otherwise be beneficial," he said.

The findings were published online July 24, 2015 in the American Heart Journal.

"Substantial Clinical Relevance"

Although RASIs after an MI are recommended by the American College of Cardiology/American Heart Association guidelines, clinicians in other specialties may worry that the medications will lead to more severe renal dysfunction or to an emergence of hyperkalemia, note the researchers.

"This is of substantial clinical relevance, since worsening renal function . . . correlates with adverse CV outcomes in patients admitted with AMI," they write. Therefore, they wanted to provide "more insight into current practice patterns."

"The main question we were really interested in was: when both indication for the drug and a relative contraindication for the drug exists, which one appears to be the dominant decision-making factor?" said Wetmore. "We had equipoise and could have seen it turning out either way."

In the analysis, records for 4223 US participants from TRIUMPH (67% men; mean age 59 years) were evaluated. All were placed into subgroups signifying the presence and severity of CKD and/or AKI, as measured by eGFR from admission-level creatinine.

The severe-CKD group had an eGFR <30 mL/min/1.73m2 (3.5%), the moderate group had an eGFR of 30 to 59 (19%), the mild group had an eGFR of 60 to 89 (46.5%), and the "no-CKD" group had an eGFR >90 (29%). The remaining patients had end-stage renal disease (ESRD) and were on dialysis (2%).

AKI was defined as having an increase in creatinine level of at least 0.3 mg/dL or 50% between baseline and end of hospital stay (12.4% of all study participants). The researchers also examined data on whether or not patients had an LVEF of less than 40% at discharge, signifying moderate to severe systolic HF (18.6%).

Among all the patients, 75.2% received a RASI prescription at discharge. As eGFR level decreased, so did RASI prescriptions; 89.3% of those with eGFR >90 mL/min/1.732 (no CKD) received prescriptions vs 52.4% of those with eGFR <30 (severe CKD) (P for trend <0.001).

In addition, significantly more of the group with no CKD and EF >40% received prescriptions (76.1%) than the group with severe CKD and EF >40% (49%, P for trend <0.001).

"Absolute prescribing rates were higher for participants with EF <40%, regardless of eGFR," report the investigators. In fact, these patients who were also in the "no-CKD" group received 13.2% more prescriptions than those without CKD and with EF >40%. The difference was 3.4% when comparing the severe-CKD groups with and without EF <40%.

"However, formal interaction testing revealed that the difference by EF across categories of renal dysfunction was not significant (P=0.40)."

Preferential Weight

Not surprisingly, AKI at discharge was also linked to fewer RASI prescriptions at discharge. Although the "formal test of interaction" of eGFR and AKI status for RASI prescribing was significant (P<0.01), the interaction of AKI and EF level was not.

Among the participants without AKI, the relative risk (RR) for less RASI use was 0.67 (95% CI 0.58–0.78) for severe CKD vs no CKD, and 0.94 (95% CI 0.90–0.99) for moderate vs no CKD. The RRs for less use were 0.84, 0.78, and 0.50 for mild, moderate, and severe CKD, respectively, with AKI.

The RRs for less RASI use were 0.75 for dialysis patients (95% CI 0.67–0.83) and 1.11 for EF <40% (95% CI 1.03–1.18).

"Our study suggests that prescribers may be preferentially weighing renal function, as opposed to EF, in their decision-making process," write the investigators.

However, they note it's important to keep in mind the study's various limitations, including the possible presence of unmeasured confounding and the use of admission creatinine to estimate eGFR for the presence of CKD, "since an impaired eGFR at time of admission may be a result of the AMI itself." Also, there were few data on postdischarge office visits and prescribing patterns.

Still, Wetmore notes that it's worth looking further into whether these drugs are being underutilized and if these patients are being overscrutinized.

"The cardiology and nephrology communities should actively work together to study the appropriate use of RAS inhibitors after [AMI]; and nephrologists, cardiologists, and hospitalists should be cognizant of the fact that it might not be appropriate for renal dysfunction to be conceived of as the barrier that it traditionally was," he said.

"In other words, practitioners should be open to the possibility that patients with decreased renal function might be good candidates for the drug and perhaps the level of ejection fraction after the AMI should be considered more heavily."

The TRIUMPH study was funded by a grant from the National Institutes of Health. Wetmore reports having served on an advisory board for Alexion and currently receives research funding from Amgen. Disclosures for the coauthors are listed in the article.

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