Angioplasty: probucol reduced subsequent deaths, MI or revascularisation.

Clinical bottom line (level 1b)

  1. Probucol reduced the number of MI, deaths and repeat revascularisations following angioplasty (NNT = 7 at 6 months) .
  2. However, diarrhoea was common (NNH = 7 at 6 months) .
  3. Multivitamins had no effect on cardiovascular events, but caused diarrhoea and yellow skin.
Tardif et al: New England Journal of Medicine 1997; 337 (6): 365-372
Expires July 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: university hospital, Canada

317 patients (aged mean 59 years, 77% male) scheduled to have standard ballon angioplasty for 50% stenosis or more of at least one coronary artery

Excluded if
  • unable to take treatment or be followed-up
  • MI in past seven days
  • scheduled for stenting or artherectomy
  • PTCA less than 6 months age or restenostic lesion
  • angioplasty of a bypass graft
  • on angiopalsty, coronary segment could not be dilated, if successful angioplasty followed by persistent sudden closure, Q-wave infarct in territory of dilated artery; emergency angioplasty required, stent inserted


    • Control Group: (n = 79, 79 analysed): placebo
    Experimental Group: (n = 80, 80 analysed): probucol 500 mg twice daily po and placebo
    Experimental Group: (n = 78, 78 analysed): multivitamins (30000 IU beta-carotene, 500 mg vitamin C and 700 IU vitamin E) twice daily po and placebo
    Experimental Group: (n = 80, 80 analysed): probucol and multivitamins
    Medication was started one month before angioplasty (injection given just before angioplasty) and continued for six months afterwards. All patients had 325 mg aspirin po daily for the study duration. Patients were specifically told not to take any other vitamin tablets.
    100% followed for 6 months

    The evidence

    placebo vs multivitamins
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death, MI, CABG or repeat angioplasty 6 months 24
    (30.4%)    		 25
    (32.1%)    		 -6%
    (-68% to 34%)    		 -1.67%
    (-16.2% to 12.8%)    		 -60
    (NNT = 6 to infinity;
    NNH = 8 to infinity)
    side effects 6 months 1
    (1.27%)    		 6
    (7.69%)    		 -508%
    (-4832% to 25%)    		 -6.43%
    (-12.8% to -0.02%)    		 -16
    (-5100 to -8)

    placebo vs probucol
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death, MI, CABG, repeat angioplasty 6 months 24
    (30.4%)    		 13
    (16.3%)    		 47%
    (3% to 71%)    		 14.1%
    (1.16% to 27.1%)    		 7
    (4 to 86)
    side effects 6 months 1
    (1.27%)    		 12
    (15.0%)    		 -1085%
    (-8799% to -58%)    		 -13.7%
    (-21.9% to -5.53%)    		 -7
    (-18 to -5)

    probucol vs probucol and multivitamins
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death, MI, CABG, repeat angioplasty 6 months 13
    (16.3%)    		 17
    (21.3%)    		 -31%
    (-151% to 32%)    		 -5.00%
    (-17.1% to 7.07%)    		 -20
    (NNT = 6 to infinity;
    NNH = 14 to infinity)
    side effects 6 months 12
    (15.0%)    		 26
    (32.5%)    		 -117%
    (-299% to -18%)    		 -17.5%
    (-30.4% to -4.59%)    		 -6
    (-22 to -3)

  • 56% of patients on multivitamins had yellow skin pigmentation.

    • Comments

    1. Probucol is a lipid-lowering agent and also has antioxidant properties. It is unclear whether these effects are due to the lipid effect or antioxidants.
    2. Note the exclusion of patients with stents may limit the usefulness of this study.

    Citation

    1. Tardif J-C, Cote G, Lesperance J, et al: Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. New England Journal of Medicine 1997; 337 (6): 365-372
    Contributor: Nick Shenker and Chris Ball, July 2000
    Reviewer: Robert McKelvie

    Clinical Question.
    Patient having angioplasty
    Intervention or Exposure probucol and multivitamins
    Comparison placebo
    Outcome MI, death, repeat revascularisation