Unstable angina: refractory: n-acetylcysteine reduced MI, but caused more symptomatic hypotension.

Clinical bottom line (level 2b)

  1. In patients with unstable angina uncontrolled by conventional therapy and admitted to CCU, adding n-acetylcysteine reduced MI (NNT = 3 at 24 hours) , but more patients had symptomatic hypotension and other side effects (NNH = 3 at 24 hours) .
  2. There was no clear effect on the incidence of chest pain or need to increase nitrate doses.
Horowitz et al: Circulation 1988; 77 (4): 787-794
Expires July 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: coronary care unit, university hospital, USA

46 patients (aged range 40 to 68 years, 70% male) unstable angina (typical chest pain at rest, associated with transient ST depression), which persisted despite medical management (verapamil, or a beta-blocker and cutaneous or slow-release transdermal nitrate- not given <6 hours before trial entry)

Excluded if
  • >75 years
  • Q-wave MI in last three months
  • non Q-wave MI in preceding seven days
  • severe hypotension (mean blood pressure <70 mmHg) before admission of nitrate or n-acetylcysteine
  • previous adverse reaction to nitrate or n-acetylcysteine
  • on medication known to affect study drugs
  • Killip class III or IV (severe left ventricular function)
  • clinically significant valvular heart disease
  • severe renal/hepatic disease


    • Note:
  • Patients were stratified according to age and prior Q-wave infarct before randomisation.


    • Control Group: (n = 22, 22 analysed): iv nitroglycerin (initially at 5 µ m/min) and placebo for 24 hours
    Experimental Group: (n = 24, 24 analysed): iv nitroglycerin (initially at 5 µ g/min) and 15 minutes later n-acetylcysteine 5 mg in 200 ml 5% dextrose iv for 24 hours
    Nitroglycerin dose adjusted if continued severe episodes of chest pain and/or systolic blood pressure >140 mmHg, or symptomatic hypotension.
    100% followed for 24 hours
    Outcome notes:
    • side effects : hypotension, headache, nausea, dizziness

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    chest pain 24 hours 20
    (90.9%)    		 19
    (79.2%)    		 13%
    (-11% to 32%)    		 11.7%
    (-8.46% to 32.0%)    		 9
    (NNT = 12 to infinity;
    NNH = 3 to infinity)
    increase in nitrate required 24 hours 11
    (50.0%)    		 8
    (33.3%)    		 33%
    (-35% to 67%)    		 16.7%
    (-11.5% to 44.8%)    		 6
    (NNT = 9 to infinity;
    NNH = 2 to infinity)
    MI 24 hours 10
    (45.6%)    		 3
    (12.5%)    		 73%
    (13% to 91%)    		 33.0%
    (8.30% to 57.6%)    		 3
    (2 to 12)
    side effects 24 hours 2
    (9.09%)    		 11
    (45.8%)    		 -404%
    (-1927% to -25%)    		 -36.7%
    (-60.0% to -13.5%)    		 -3
    (-7 to -2)

  • No patients received aspirin.

    • Comments

    1. Very short follow-up- unclear whether benefits persist.

    Citation

    1. Horowitz JD, Henry CA, Syrjanen Ml, et al: Combined use of nitroglycerin and N-acetylcysteine in the management of unstable angina pectoris. Circulation 1988; 77 (4): 787-794
    Contributor: Nick Shenker and Chris Ball, July 2000
    Reviewer:

    Clinical Question.
    Patient refractory angina
    Intervention or Exposure n-acetylcysteine
    Outcome pain, death, side effects