Unstable angina: ticlopidine decreased nonfatal MI but not cardiovascular mortality.

Clinical bottom line (level 1b)

  1. Patients who were given ticlopidine were less likely to have a nonfatal MI, than those given conventional therapy alone (NNT = 24 at 6 months) .
  2. Patients with unstable angina who were given ticlopidine as well as conventional therapy had no clear difference in fatal MI and vascular disease, than those given conventional therapy alone.
Balsano et al: Circulation 1990; 82 (1): 17-26
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: multicentre (coronary care units), Italy

624 patients (aged mean 60 years, 72% male) presented with symptoms suggesting unstable angina (defined as new onset or sudden worsening of effort angina without increased physical activity during the last month; new onset or worsening, less than a month earlier, of angina at rest, still present in the week before admission, with at least one episode lasting >15 minutes; angina attacks at rest, at least one of which lasted >15 minutes in the 12 hours before admission)

Excluded if
  • acute MI in progress or in the previous 6 weeks
  • lack of defined ECG criteria
  • no evidence of ischaemic heart disease or unstable angina
  • previous aortocoronary bypass or scheduled within the next 3 months
  • antiplatelet agents, anticoagulants or fibrinolytic agents still given during the previous 4 days
  • peptic ulcer symptoms
  • probable low compliance
  • variant angina
  • age >75 years
  • tachyarrhythmia
  • congestive heart failure
  • valvular heart disease
  • uncontrolled severe hypertension (diastolic blood pressure >115 mmHg)
  • hepatic or renal failure
  • bleeding conditions or at haemorrhagic risk
  • hypotension (systolic blood pressure <90 mmHg)
  • severe respiratory failure
  • concomitant illness that might affect 1 year survival
  • previous or concomitant haematologic disorders
  • thyrotoxicosis
  • fever ( = 39 ° C)
  • known intolerance or allergy to ticlopidine
  • pregnancy
  • high dose oral contraceptive


    • Control Group: (n = 338, 338 analysed): continued conventional therapy alone
    Experimental Group: (n = 314, 314 analysed): ticlopidine , 250 mg, plus conventional therapy
    All patients were given conventional treatment.
    82.5% followed for 24 weeks

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    fatal MI or vascular death 6 months 16
    (4.73%)    		 8
    (2.55%)    		 46.0%
    (-24.0% to 77.0%)    		 2.19%
    (-0.67% to 5.04%)    		 46
    (NNT = 20 to infinity;
    NNH = 149 to infinity)
    nonfatal MI 6 months 30
    (8.88%)    		 15
    (4.78%)    		 46.0%
    (2.00% to 70.0%)    		 4.10%
    (0.26% to 7.94%)    		 24
    (13 to 389)

  • 15 adverse gastrointestinal reactions to ticlopidine occurred (10 requiring discontinuation). There were also 6 skin reactions (5 requiring discontinuation), and 4 minor bleeding disorders. In the control group, 13 central and peripheral nervous system disorders were seen (7 requiring therapy change), 3 gastrointestinal disorders (1 needing change) and 11 peripheral oedema ( 6 therapy changes).

    • Comments

    1. Lack of control for other antiplatelet agents reflects the state of knowledge at the time, but probably does not alter the underlying conclusions

    Citation

    1. Balsano F, Rizzon P, Violi F, et al: Antiplatelet treatment with ticlopidine in unstable angina: A controlled multicenter clinical trial. Circulation 1990; 82 (1): 17-26
    Contributor: Clare Wotton and Bob Phillips, January 2000
    Reviewer: Andreas Michaelides

    Clinical Question.
    Patient unstable angina
    Intervention or Exposure ticlopidine
    Comparison conventional therapy alone
    Outcome vascular death and nonfatal MI