Angioplasty: stenting: clopidogrel led to fewer complications than ticlopidine

Clinical bottom line (level 1b)

  1. Patients following coronary artery stenting who received clopidogrel and aspirin compared with ticlopidine and aspirin were less likely to have a complication (NNT = 22 at 4 weeks) .
  2. Patients who received a loading dose of clopidogrel compared with no loading dose were less likely to have complications (NNT = 30 at 4 weeks) .
  3. There was no clear difference in cardiac adverse events between any of the groups.
Bertrand et al: Circulation 2000; 102 : 624-629
Expires March 2004

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 48 acute hospitals, 8 countries in Europe

1020 patients (aged mean 60, 77% male) undergone successful coronary artery stenting

Excluded if
  • > 1 vessel stented or > 2 stents used
  • PTCA or CABG within previous 2 months
  • thrombolytics within 2 weeks
  • known allergy or intolerance to study medication
  • > 10% residual stenosis
  • creatine kinase levels > twice normal before or after procedure
  • unable to start study drug within 6 hours
  • stenting involved left main coronary artery or a major bifurcation, or vein grafts
  • primary angioplasty for myocardial infarction
  • persistent objective ischaemia post-procedure
  • oral anticoagulants or antiplatelet agents (except aspirin) given in previous month, or need following procedure

Control Group: (n = 340, 340 analysed): ticlopidine 250 mg twice daily and aspirin 325 mg daily for 28 days
Experimental Group: (n = 335, 335 analysed): clopidogrel 75 mg daily and aspirin 325 mg daily for 28 days
Experimental Group: (n = 345, 345 analysed): clopidogrel loading dose 300 mg, followed by 75 mg daily, and aspirin 75 mg daily
Heparin was stopped at the end of the procedure and 4 hours before sheath removal.
100% followed for 4 weeks
Outcome notes:
  • complications : major peripheral or bleeding complications, neutropenia, thrombocytopenia, or early discontinuation of study drug due to noncardiac advers event
  • cardiac adverse events : cardiac death, myocardial infarction, target lesion revascularisation

The evidence

ticlopidine v. clopidogrel
Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
complications 4 weeks 31
(9.12%)		 31
(4.56%)		 50%
(16% to 69%)		 4.56%
(1.12% to 8.00%)		 22
(13 to 89)
cardiac adverse events 4 weeks 3
(0.88%)		 9
(1.32%)		 -50%
(-450% to 59%)		 -0.44%
(-1.75% to 0.87%)		 -230
(NNT = 120 to infinity;
NNH = 57 to infinity)

clopidogrel loading dose v. clopidogrel fixed dose
Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
complications 4 weeks 21
(6.27%)		 10
(2.90%)		 54%
(3% to 78%)		 3.37%
(0.23% to 6.51%)		 30
(51 to 440)
cardiac adverse events 4 weeks 5
(1.49%)		 4
(1.16%)		 22%
(-190% to 79%)		 0.33%
(-1.39% to 2.05%)		 300
(NNT = 49 to infinity;
NNH = 72 to infinity)

Comments

  1. The study was too small to show any difference between the two drugs for cardiac adverse events.

Citation

  1. Bertrand ME, Rupprecht H-J, Urban P, et al: double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation 2000; 102 : 624-629
Search Terms: from ACP Journal Club other articles noted
Contributor: Chris Ball, March 2002
Reviewer:

Clinical Question.
Patient coronary artery stenting
Intervention or Exposure clopidogrel and aspirin
Comparison ticlopidine and aspirin
Outcome bleeding, thrombocytopenia, neutropenia, cardiac complications