Unstable angina: intravenous nitrates reduced angina attacks.

Clinical bottom line (level 1b)

  1. Patients with unstable angina who were on iv nitroglycerin, had fewer angina attacks (NNT = 6 at 48 hours) and require fewer sublingual nitroglycerin tablets (NNT = 7 at 48 hours) .
  2. Side effects like headache and hypotension forced a number of patients to stop the infusion (NNH = 10 at 48 hours) .
Karlberg et al: Journal of Internal Medicine 1998; 243: 25-31
Expires July 2003

The study

Double-blinded concealed randomised trial without intention-to-treat
Setting: coronary care unit, university hospital, Sweden

143 patients (aged range 41 to 84 years; mean 66, 71% male) unstable angina, defined as recent onset chest pain suggestive of myocardial ischaemia or worsening of previously stable angina (pain occurred at rest or with minimal effort at the last attack within 24 hours) and clinical evidence of underlying coronary artery disease- one of:
  • new ST depression or T wave inversion in two contiguous leads
  • positive exercise stress test
  • history of previous acute MI


Excluded if
  • ST elevation suggestive of acute MI
  • systolic blood pressure <100 mmHg
  • heart rate >100 bpm
  • serious arrhythmia
  • aortic stenosis
  • CK-MB fraction >0.8
  • proven non-ischaemia cause of chest pain


    • Note:
  • Patients were stratified for NSAID use before randomisation.


    • Control Group: (n = 70, 70 analysed): placebo
    Experimental Group: (n = 73, 73 analysed): iv nitroglycerin 1 mg/min, titrated from 1.5 ml/hr to 12 ml/hr. If 20% reduction in blood pressure or 10% decrease in heart rate, or headache, titration stopped at that level. Infusion continued until: end of 48 hour study period; patient developed chest pain >20 minutes despite three sublingual nitroglycerin tablets; patient wanted to discontinue
    During first two hours, patients had morphine for chest pain. After two hours, patients had nitroglycerin for chest pain, and received aspirin and a beta-blocker if not contraindicated.
    100% followed for 48 hours
    Outcome notes:
    • ongoing myocardial ischaemia : two or more angina attacks responding to 1-3 sublingual nitroglycerin tablets and lasting <20 minutes; one angina attack lasting >20 minutes despite three sublingual nitroglycerin tablets
    • sublingual nitroglycerin use : more than two tablets
    • intolerable side effects : causing discontinuation of infusion

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    ongoing myocardial ischaemia 48 hours 25
    (35.7%)    		 13
    (17.8%)    		 50%
    (11% to 72%)    		 17.9%
    (3.66% to 32.2%)    		 6
    (3 to 27)
    sublingual nitroglycerin use 48 hours 22
    (31.4%)    		 12
    (16.4%)    		 48%
    (3% to 72%)    		 15.0%
    (1.19% to 28.8%)    		 7
    (3 to 84)
    intolerable side effects 48 hours 0
    (0.00%)    		 7
    (9.59%)    		 100%
    (% to %)    		 -9.59%
    (-16.3% to -2.83%)    		 -10
    (-35 to -6)

    Comments

    1. Short follow-up- what effect might iv nitrates have on mortality and time in hospital? Do nitrates just delay problems?
    2. Yusuf et al showed that iv nitrates reduce mortality in patients with acute MI.

    Citation

    1. Karlberg KK, Saldeen T, Wallin R, et al: Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study. Journal of Internal Medicine 1998; 243: 25-31
    Search Terms: angin* and (nitroglyc* or nitrat* or trinitr*)
    Contributor: Chris Ball and Clare Wotton, July 2000
    Reviewer: William Rhoton

    Clinical Question.
    Patient unstable angina
    Intervention or Exposure iv nitrates
    Outcome pain, side effects