ACT

Published

ACT Investigators. "Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Angiography". Circulation. 2011. 124:1250-1259.
PubMed • Full text • PDF

Clinical Question

Among patients undergoing coronary and peripheral vascular angiography, does acetylcysteine reduce the risk of contrast-induced acute kidney injury?

Bottom Line

Acetylcysteine does not prevent contrast-induced acute kidney injury in patients undergoing angiography.

Major Points

Acetylcysteine reduces oxidative stress and may improve renal perfusion. Numerous small or otherwise low-quality trials have been published investigating whether acetylcysteine reduced the incidence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing angiography.

Published in 2011, the multi-centered Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT) was aimed to address these deficiencies in previous studies. The study was triple-blinded with proper allocation concealment, and enrolled a total of 2,308 patients with one risk factor for CI-AKI to acetylcysteine 1200mg orally every 12 hours for two doses before and after angiography. The primary endpoint of CI-AKI, defined as 25% elevation of serum creatinine above baseline at 48-96 post-angiography, did not differ between groups.

This publication provided a meta-analyses of high-quality data, which found no benefit in prevention of CI-AKI when acetylcysteine was given with IV contrast (RR 1.05; 95% CI 0.73-1.53). (Including low-quality data found benefit, however.) Similarly, a 2013 NICE evidence summary deemed that overall there is low- to very-low quality evidence for benefit of NAC in prevention of CI-AKI. The corresponding guidelines do not make recommendations on the use of NAC for prevention of CI-AKI.

Guidelines

ACCF/AHA/SCAI PCI (2011, adapted)

• Patients should be assessed for risk of CI-AKI before PCI (class I, level of evidence C)
• Adequately hydrate patients before they undergo cardiac catheterization with contrast (class I, level of evidence C)
• Minimize the volume of contrast media if CKD (CrCl <60 mL/min) (class I, level of evidence B)
• Acetylcysteine is not useful in the prevention of CI-AKI (class III, level of evidence A)

Design

• Multicenter, randomized, triple-blinded, randomized control trial
• N=2308
  • Acetylcysteine (n=1172)
  • Placebo (n=1136)
• Setting: 46 sites in Brazil
• Enrollment: 2008-2010
• Follow-up: 30 days (up to 96 hours for the primary outcome)
• Analysis: Intention-to-treat
• Primary outcome: Contrast-induced acute kidney injury 48-96h post-angiography

Population

Inclusion Criteria

• Undergoing coronary or peripheral arterial diagnostic intravascular angiography or PCI
• ≥1 risk factor for CI-AKI:
  • Age >70 years
  • CKD, defined by creatinine >132.6 umol/L (1.5 mg/dL)
  • DM
  • Clinical evidence of HF or LVEF <45%
  • Hypotension (not further defined)

Exclusion Criteria

• Patients on dialysis
• STEMI undergoing PCI (could not receive hydration procedure 6h pre-procedure)
• Women who were pregnant, breastfeeding, <45 years without use of contraception

Baseline Characteristics

From the acetylcysteine group

• Demographics: Age 68y, 38% female
• Vitals: Weight 73 kg
• Laboratory results: Creatinine 1.2 mg/dL
• Diagnosis: ACS 36%, HTN 86%
• Medications: NSAIDs 5%, ACE-inhibitor 60%, diuretics 38%, metformin 31%
• Inclusion Criteria:
  • Serum Cr > 1.5mg/dL: 15%
  • Diabetes mellitus: 61%
  • Known heart failure: 10%
  • Hypotension: <1%
  • Age > 70y: 51%
• Estimated GFR: 69 ml/min/1.73 m²
  • <30: 5%
  • 30-60: 36%
  • >60: 58%
• Procedure Type: Peripheral vascular angiography 3%, coronary diagnostic angiography 66%, percutaneous coronary intervention 30%, none because of cancellation 1%
• Hydration Before Procedure
  • NaCl 0.9%, any scheme: 93%
  • NaCl 0.9%, 1mL/kg/h for 6h: 47%
  • Bicarbonate 0.9%: 5%
• Hydration After Procedure
  • NaCl 0.9%, any scheme: 98%
  • NaCl 0.9%, 1mL/kg/h for 6h: 69%
  • Bicarbonate 0.9%: 6%
• Contrast Type: High osmolarity 22%, low osmolarity 75%, iso-osmolarity 3%
• Contrast Volume: 100mL

Interventions

• All groups received hydration 6-12 hours pre and post angiography
  • 0.9% saline at 1 mL/kg/h was recommended but could be substituted
• Acetylcysteine arm received:
  • 1200mg acetylcysteine q12h for 2 doses before and after the procedure
• Placebo arm received:
  • powder that had the same appearance, taste, and smell as acetylcysteine powder

Outcomes

Presented as acetylcysteine vs. placebo.

Primary Outcome

Contrast Induced Acute Kidney Injury

Defined as a rise in creatinine ≥25% above baseline at 48-96h.

12.7% vs. 12.7% (RR 1.00; 95% CI 0.81-1.25; P=0.97)

Secondary Outcomes

Doubling in serum creatinine at 48-96 hours

1.1% vs. 1.5% (RR 0.74; 95% CI 0.36-1.52; P=0.41)

Elevation in creatinine at 48-96 hours

≥0.5 mg/dL (≥44.2 umol/L): 3.9% vs. 3.8% (RR 1.04; 95% CI 0.69-1.57; P=0.85)

≥0.3 mg/dL (≥13.3 umol/L): 12.1% vs. 11.0% (RR 1.10; 95% CI 0.88-1.39; P=0.39)

All-cause mortality at 30 days

2.0% vs. 2.1% (HR 0.97; 95% CI 0.54-1.73; P=0.92)

Or need for HD: 2.2% vs. 2.3% (HR 0.97; 95% CI 0.56-1.69; P=0.92)

Or doubling of creatinine: 3.2% vs. 3.6% (HR 0.90; 95% CI 0.58-1.39; P=0.63)

Need for HD

0.3% vs. 0.3% (HR 0.87; 95% CI 0.17-4.35; P=0.86)

CV mortality

1.5% vs. 1.6% (HR 0.99; 95% CI 0.51-1.90; P=0.97)

Subgroup Analysis

There was no difference in the primary outcome for age, sex, baseline creatinine, diabetes, volume of contrast agent, ACS, type of contrast, timing of post-angiography serum creatinine, eGFR level, or CKD with diabetes.

Adverse Events

Serious

1.3% vs. 2.2% (P=0.09)

Vomiting

0.3% vs. 1.2% (P=0.02)

No other adverse events reached statistical significance.

Criticisms

• Lower proportion of the primary outcome than expected
• The average volume of contrast used was low (100mL) and may have prevented CI-AKI
• Relatively short duration of acetylcysteine use

Funding

• Brazilian Ministry of Health