Chest pain: patients with non-specific recurrent chest pain benefited from imipramine.

Clinical bottom line (level 1b)

  1. Patients with normal coronary arteries and chest pain may be found to have multiple potential causes on exhaustive testing.
  2. Patients given imipramine had 50% fewer episodes of chest pain after three weeks compared with those on placebo.
  3. Whether drug side-effects are a problem was unclear.
Cannon et al: New England Journal of Medicine 1994; 330 (20): 1411-1417
Expires Unknown Month 2001

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: quaternary referral centre, USA

60 patients (aged range 29 to 72 years; mean 50, 67% female) referred with recurrent non-specific chest pain and;
  • normal coronary angiogram with no epicardial artery spasm after ergonovine 0.15 mg iv
  • normal left ventricular function at rest
  • no evidence of left ventricular hypertrophy or valvular heart disease
  • blood pressure 160/100 mmHg or less without medication
  • no musculoskeletal discomfort

Control Group: (n = 20, 20 analysed): placebo
Experimental Group: (n = 20, 20 analysed): clonidine 0.05 twice daily for one week, then 0.1 mg twice daily for two weeks
Experimental Group: (n = 20, 20 analysed): imipramine 25 mg nocte for one week and placebo, then 50 mg nocte and placebo for two weeks
All patients discontinued all medication possible one week before study. Patients underwent internal pacing, oesophageal motility testing and psychiatric assessment. Patients were placed on placebo for five weeks before being randomised.
100% followed for 3 weeks

The evidence

Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
clonidine side effects 3 weeks 11
(55.0%)		 14
(70.0%)		 -27%
(-108% to 22%)		 -15.0%
(-44.6% to 14.6%)		 -7
(NNT = 7 to infinity;
NNH = 2 to infinity)
imipramine side effects 3 weeks 11
(55.0%)		 15
(75.0%)		 -36%
(-118% to 15%)		 -20.0%
(-48.9% to 8.91%)		 -5
(NNT = 11 to infinity;
NNH = 2 to infinity)

Outcome Control Group
(SD)		 Experimental Group
(SD)		 Mean Difference
(95% CI)
placebo vs. clonidine: % reduction in frequency of episodes of chest pain (SD) 1
(86) 		39
(51) 		38
(-7 to 83)
placebo vs imipramine: % reduction in frequency of episodes of chest pain (SD) 1
(86) 		52
(25) 		51
(10 to 91)

  • chest pain reproduced by:
    • right ventricular stimulation or infracoronary adenosine: 52/60: 87% (95% CI: 78% to 95%)
    • abnormal oesophageal motility: 38/60: 63% (95% CI: 51% to 76%)
    • psychiatric disorder: 22/54: 40% (95% CI: 28% to 54%)
    • exercise leading to ischaemic ECG: 13/60: 22% (95% CI: 11% to 32%)

    • Comments

    1. The study was not large enough to demonstrate an increase in side effects.

    Citation

    1. Cannon RO, Quyyumi AA, Mincemoyer R, et al: Imipramine in patients with chest pain despite normal coronary angiograms. New England Journal of Medicine 1994; 330 (20): 1411-1417
    Search Terms: chest pain in Cochrane
    Contributor: Chris Ball and Clare Wotton, Unknown Month 2000
    Reviewer:

    Clinical Question.
    Patient chest pain
    Intervention or Exposure imipramine
    Comparison placebo
    Outcome episodes of chest pain, side effects