ACTOVMC LANDMARK TRIALS SERIES

 "Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Angiography". Circulation. 2011.

124:1250-1259.

Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)

BACKGROUND

SOME FACTS: Acetylcysteine reduces oxidative stress

and may improve renal hemodynamics However, it remains uncertain whether

Acetylcysteine can prevent contrast induced AKI

PRIOR TO THIS TRIAL: Many studies prior to the ACT trial have

shown conflicting results on the role of acetylcysteine and the benefits

CLINICAL QUESTION

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

DESIGN

Analysis: Intention-to-treat Multicenter, randomized, triple-blinded, randomized control trial N=2308

Acetylcysteine (n=1172) Placebo (n=1136)

Setting: Brazil, 46 sites Enrollment: 2008-2010 Follow-up: 30 days (up to 96 hours for the primary outcome) 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 > 1.5 mg/dL Diabetes 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

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 powd

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

BOTTOM LINE

Acetylcysteine DOES NOT prevent contrast-induced acute kidney injury in patients undergoing

angiography

DISCUSSION QUESTIONS

What type of patients were excluded in the ACT study?

What question did the ACT address? For a patient undergoing PCI (who dose not

have a STEMI), should he/she receive acetylcysteine to protect against contrast induced nephropathy?

DISCUSSION QUESTIONS/ANSWERS

What type of patients were excluded in the ACT study? ANSWER: Patient undergoing dialysis, STEMI patients (unable to get fluid hydration

prior to PCI), pregnant/breastfeeding What question did the ACT address?

ANSWER: For patients undergoing angiography, should acetylcysteine be given to prevent contrast nephropathy

For a patient undergoing PCI (who dose not have a STEMI), should he/she receive acetylcysteine to protect against contrast induced nephropathy? ANSWER: According to ACT, no because data does not show benefit

BOARD-LIKE QUESTION

81yo M, hospitalized for NSTEMI and scheduled for PCI in AM. Patient has a history of HTN, HLD, DM2, and CKD. Medications include Lisinopril, Atorvastatin, Insulin, Aspirin.On PE, HR 78, BP 148/82. JVP 6. CV showed RRR. Lungs clear. LE with 1+ pitting edema.Labs: Creatinine 2.7 (baseline)GFR 31UA showed 2+ protein

(QUESTION ADAPTED from MKSAP 17)

QUESTIONWhat would help prevent kidney injury in this patient?A. Start IV fluidsB. Give oral N-acetylcysteineC. Discontinue AspirinD. Discontinue Lisinopril

BOARD-LIKE QUESTIONEducational Objective: Recognition and Management of patients who are at risk for contrast-induced nephropathy (CIN)

Key Point:- Risk factors for CIN include: >75yo, DM2,

CKD, decreased renal perfusion, concurrent use of nephrotoxic drugs

- IV NS be started prior to contrast exposure (but also be vigilant of rate of fluids in patients with heart failure)

- N-acetylcysteine in patients at risk for CIN remains inconsistent and are not recommended

ANSWERWhat would help prevent kidney injury in this patient?A. Start IV fluidsB. Give oral N-acetylcysteineC. Discontinue AspirinD. Discontinue Lisinopril