NAC and/or Sodium Bicarbonate Fail to Add Protection Against Acute Kidney Damage in STEMI

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N-acetylcysteine (NAC) and sodium bicarbonate, singularly or in combination, do not add any protection over standard hydration alone against contrast-induced nephropathy (CIN) after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, according to a study published online April 8, 2014, ahead of print in Circulation: Cardiovascular Interventions, the combination treatment may reduce the risk of renal dysfunction at 30 days.

For the CINSTEMI (Contrast-induced Nephropathy in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention) trial, researchers led by Per Thayssen, MD, DMSci, of Odense University Hospital (Odense, Denmark), randomized 720 STEMI patients undergoing primary PCI to receive standard hydration therapy alone (n = 181; 0.9% sodium chloride intravenously ≥ 60 mL/h for at least 6 hours) or with:

• NAC 1,200 mg orally before PCI, followed by 1,200 mg daily for 48 hours (n = 176)
• Sodium bicarbonate 167 mmol/L intravenously as 500 mL in the first hour, followed by infusion of 100 mL/hour in the next 5 hours (n = 181)
• Combination therapy of NAC plus sodium bicarbonate (n = 177)

Patients were treated from May 2010 to March 2012 at 3 Danish hospitals.

At 3 days postprocedure, the overall incidence of CIN (rise in serum creatinine [SCr] ≥ 25% from baseline; primary endpoint) was 21.9%. There were no differences between the NAC, sodium bicarbonate, combined, and standard treatment groups (table 1). Additionally, the primary endpoint did not differ among patients with or without reduced creatinine clearance at baseline (22.4% vs 17.5%; P = 0.360).

However, for the secondary endpoint of increase in SCr concentration of at least 25% between admission and day 30, there was a trend toward a lower rate in patients treated with combined therapy. Moreover, only combined treatment reduced the risk of renal dysfunction at 30 days compared with standard therapy (P = 0.005).

Table 1. Primary and Secondary Endpoints

In patients who developed CIN, persistent renal damage occurred in almost half (48.2%) with no differences between the treatment groups (P = 0.150). No patients had renal failure requiring dialysis.

Clinical outcomes were low and balanced among the groups at both 3 and 30 days postprocedure. Overall MACE (cardiac death, MI, TVR) at 30 days was 1.8%, with no major differences among the NAC (0.0%), sodium bicarbonate (3.6%), combined (1.7%), or standard treatment (2.2%) cohorts (P = 0.127).

Combination Therapy Could be ‘Potent’

“The reason for contrast-induced renal impairment still remains unclear, but vasoconstriction because of tubular damage and oxidative stress, which together with increased interstitial renal pressure, lead to medullary hypoperfusion, and lowered glomerular filtration may contribute significantly,” Dr. Thayssen and colleagues write. “These changes occur because of cytotoxity and increased viscosity of the contrast media…. But the matter of which type of contrast media [is] most kidney-friendly is still under debate.”

They suggest that, “From a theoretical point of view, the combination of NAC and [sodium bicarbonate] might be the superior strategy because these drugs in combination may exert a potent antioxidative effect and by this, reduce the harmful consequence of contrast media.”

Working the Kinks Out of Hydration

In a telephone interview, Somjot S. Brar, MD, MPH, of Kaiser Permanente (Los Angeles, CA), told TCTMD that the CINSTEMI trial was notable because of its patient population. “What wasn’t really known before was the utility of possibly using this in patients with STEMI,” he noted. “It’s informative to know that the results in the STEMI population are similar to the results in other ACS populations.”

Although hydration in general has been shown to effectively prevent CIN, “the challenge,” Dr. Brar said, “is that nobody really knows how to hydrate.” How long hydration should last and the rate at which a patient is hydrated have yet to be fully established, he explained, adding, “It’s not really clear how [the study authors] decided on [their hydration] metrics.”

Also, since CIN affected about 1 in 5 study patients in CINSTEMI, comparable to real-world practice, he suggested that the rationale behind this study was “to identify adjunctive therapies that could bring that rate down even further.”

Lastly, Dr. Brar noted that the patient population did not have a high rate of chronic kidney disease, “yet the incidence of contrast nephropathy was pretty high…. Whether that’s because patients with STEMI are at particularly high risk of acute kidney injury, or whether that’s a reflection of a definition of contrast nephropathy that is too sensitive, isn’t really known from what is reported here.”

 

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Source:
Thayssen P, Lassen JF, Jensen SE, et al. Prevention of contrast-induced nephropathy with N-acetylcysteine or sodium bicarbonate in patients with ST-segment myocardial infarction: a prospective, randomized, open-labeled trial. Circ Cardiovasc Interv. 2014;Epub ahead of print.

 

 

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