- 1 Clinical Question
- 2 Bottom Line
- 3 Major Points
- 4 Guidelines
- 5 Design
- 6 Population
- 7 Interventions
- 8 Outcomes
- 9 Criticisms
- 10 Funding
- 11 Further Reading
Among patients undergoing coronary and peripheral vascular angiography, does acetylcysteine reduce the risk of contrast-induced acute kidney injury?
Acetylcysteine does not prevent contrast-induced acute kidney injury in patients undergoing angiography.
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.
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)
- Multicenter, randomized, triple-blinded, randomized control trial
- 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
- 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)
- Clinical evidence of HF or LVEF <45%
- Hypotension (not further defined)
- 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
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
- 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
Presented as acetylcysteine vs. placebo.
- 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)
- 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)
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.
- 1.3% vs. 2.2% (P=0.09)
- 0.3% vs. 1.2% (P=0.02)
No other adverse events reached statistical significance.
- 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
- Brazilian Ministry of Health
- Drager LF, et al. "Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury." Nephrol Dial Transplant. 2004;19(7):1803-1807.
- Lopez BL, et al. "N-acetylcysteine enhances endothelium-dependent vasorelaxation in the isolated rat mesenteric artery." Annals of Emergency Medicine. 1998;32(4):405-410.
- NICE authors. "Acute Kidney Injury: Prevention, detection, and management up to the point of renal replacement therapy." NICE Clinical Guidelines. 2013;No. 169.
- Levine GN, et al. "2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention." Circulation. 2011;124:e574-e651.
- McCullough PA, et al. "Minimizing the renal toxicity of iodinated contrast." Circulation. 2011;124(11):1210-1211.