AKI post-AMI tied to more serious kidney outcomes

Patients who develop acute kidney injury (AKI) following an acute myocardial infarction (AMI) have an elevated risk of more serious kidney outcomes including persistent reductions in estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or renal death, according to results of the PARADISE-MI trial.

The double-blind, event-driven PARADISE-MI trial involved 5,661 patients who experienced an AMI (0.5–7 days with left ventricular ejection fraction ≤40 percent and/or pulmonary congestion) and who had ≥1 risk factor for heart failure (HF) or death*. They were randomized 1:1 to receive sacubitril/valsartan at a target dose of 97/103 mg BID or ramipril at a target dose of 5 mg BID. Patients with clinical instability, baseline eGFR <30 mL/min/1.73 m², or a history of HF were excluded. The median follow-up period was 1.8 years.

AKI, defined as an increase in serum creatinine by ≥0.3 mg/dL from baseline to day 7, occurred in 5.3 percent of the 5,207 patients with available data (n=275). [ASN Kidney Week 2021, abstract P02545]

At baseline, compared with patients without AKI, those with AKI were older (mean age 67 vs 63 years; p<0.001), had higher systolic blood pressure levels (124 vs 121 mm Hg; p<0.001), and were more like to have diabetes (50 percent vs 42 percent; p=0.01), hypertension (73 percent vs 64 percent; p=0.005), atrial fibrillation or flutter (19 percent vs 14 percent; p=0.01), pulmonary congestion (62 percent vs 54 percent; p=0.01), a history of stroke (8 percent vs 4 percent; p=0.01), and Killip class ≥II (68 percent vs 58 percent; p=0.001).

Those with AKI were also more likely to have lower eGFR levels than those without AKI (66 vs 72 mL/min/1.73 m²), and a greater proportion were on diuretics (65 percent vs 43 percent) or mineralocorticoid receptor antagonists (55 percent vs 41 percent; p<0.001 for all).

AKI occurred more frequently in the sacubitril/valsartan compared with the ramipril arm (6.0 percent vs 4.6 percent; odds ratio, 1.32, 95 percent confidence interval [CI], 1.03–1.68).

The kidney composite outcome was defined as a persistent ≥50 percent reduction in eGFR from baseline, ESRD, or renal death. This was a rare event, occurring in 0.7 percent (n=37) of the study population, and did not differ between those who received sacubitril/valsartan or ramipril (p=0.25). However, those with AKI were at greater risk at developing the kidney composite outcome than those without AKI (4.0 percent vs 0.5 percent; adjusted hazard ratio [adjHR], 8.4, 95 percent CI, 3.9–17.9). Treatment arm did not appear to modify the effect (p_interaction=0.71).

The cardiovascular (CV) composite outcome of CV death, first hospitalization for HF, or outpatient HF occurred in 11.2 percent of patients (n=585). While numerically higher in patients with vs without AKI (17.8 percent vs 10.9 percent), AKI was not significantly associated with the CV outcome (adjHR, 1.2, 95 percent CI, 0.9–1.7).

“AKI is a potent predictor of future development of the composite renal outcome. Although there were more AKI events within the first week in the sacubitril/valsartan arm, the frequency of longer-term renal composite events was not different according to randomized treatment,” said the authors. In addition, adjusted analysis showed that AKI was not associated with the composite CV outcome.

It remains to be seen if “strategies aimed at mitigating short-term AKI risk post-MI translate into longer term kidney protection,” they added.