Source: Eur Urol  |  Posted 5 years ago

By Chris Berrie

BRUSSELS, BELGIUM -- May 19, 2006 -- The thienopyridine agent ticlopidine, used in combination with aspirin in patients with previous ischaemic stroke or transient ischaemic attack (TIA), results in a favourable outcome trend and acceptable risk, according to a randomised, multicentre, double-blind, parallel-group trial.

Principal investigator Carmine Marini, MD, professor of neurology, University of L'Aquila, L'Aquila, Italy, presented these results here on May 17[^]th[] on behalf of the Ticlopidine and Aspirin Combination for Stroke (TACS) study group at the 15[^]th[] European Stroke Conference (ESC).

"I think that there is widespread agreement on the hypothesis that the combination of aspirin and thienopyridines might lead to additive effects in the prevention of vascular events," Dr. Marini said. Indeed, recent trials of aspirin and clopidogrel combinations have given indications of benefit over either agent alone for patients at high risk or with previous stroke or TIA.

The inclusion criteria for Dr. Marini's study were either ischaemic stroke (including retinal and lacunar infarctions) with focal neurological deficit likely to be atherothrombotic, within 1 week and 3 months of randomisation, or TIA of acute onset with focal neurological signs that showed recovery after 30 minutes to 24 hours, within 6 months of randomisation. Exclusion criteria related primarily to age and patient survival potential, along with contraindications to aspirin or ticlopidine.

The 218 patients enrolled underwent a centralised randomisation with stratification by TIA/stroke and clinical center. Treatment regimens consisted of aspirin 100 mg/day with either placebo (n = 109) or ticlopidine 500 mg/day (n = 109), with mandatory computed tomography scans for patients with new strokes. The primary endpoint was a combined outcome event of any stroke (ischaemic, haemorrhagic, or unknown), myocardial infarction (MI), or vascular death (including any fatal haemorrhage).

The combined baseline characteristics showed a mean age of 69.9 years, 59.6% male, with 21.1% diagnosed as TIA and 78.9% as stroke. The average follow-up was 20.1 months (range, 12-60 months).

The trial of ORG 10172 in acute stroke treatment (TOAST) classification of the index event showed no significant differences between the 2 treatment groups. There were no significant differences in the risk factor distribution by treatment, although the aspirin alone group saw a trend for less atrial fibrillation (3.8%, vs 8.3% for aspirin plus ticlopidine; []P[] =.15) and diabetes mellitus (23.4% vs 32.1%; []P[] =.20).

The other factors included (respectively): smoking (20.2% vs 21.3%); alcohol consumption (33.6% vs 33.9%); arterial hypertension (78.5% vs 76.2%); hypercholesterolaemia (3.3% vs 30.1%); hypertriglyceridaemia (37.0% vs 37.9%); coronary heart disease (23.4% vs 24.8%); peripheral artery disease (3.7% vs 4.7%); and carotid stenosis (16.5% vs 18.3%).

The intention-to-treat analysis for the combined outcome showed a beneficial trend for the aspirin plus ticlopidine over aspirin alone group (risk ratio, 0.65; 95% confidence interval, 0.32-1.32). This beneficial effect of the addition of ticlopidine to aspirin was seen as a trend when the cohort was broken into subgroups (ischaemic stroke, all strokes, MI, vascular death, and all deaths), except for an inverse trend seen for haemorrhagic stroke.

Adverse events according to treatment showed no significant differences between treatment groups, although there were adverse trends for ticlopidine relating to ecchymosis (1.8% vs 5.5% with ticlopidine; []P[] =.31); haematuria (0.9% vs 2.8%; []P[] =.36); epistaxis (2.8% vs 3.7%; []P[] =.51); any haemorrhage (11.9% vs 16.5%; []P[] =.44); skin rash (0.9% vs 5.5%; []P[] =.15); diarrhoea (2.8% vs. 4.6%; P =.26); leukopenia (0.0% vs 1.8%); and liver enzyme elevation (17.4% vs 31.2%; []P[] =.06).

Conversely, a trend in favor of the combination arm was seen for incidence of glottis oedema (0.9% vs 0.0%; []P[] =.32); neutropenia (3.7% vs 1.8%; []P[] =.54); thrombocytopenia (3.7% vs 1.8%; []P[] =.41); and hyperbilirubinaemia (9.2% vs 4.6%).

No differences were seen between the arms for gastrointestinal haemorrhage, epigastralgia and anaemia, as was the case for the full range of serious adverse events followed.

Dr. Marini concluded that the combination of ticlopidine and aspirin in patients with previous TIA or stroke showed an acceptable risk with a favourable trend for the primary endpoint of a combined outcome event of stroke, MI, or vascular death. "This indicates that large clinical trials for the combination of thienopyridines and aspirin should be performed in patients with TIA and stroke," he said.

The study drugs were supplied by Vecchi & C Piam, Genova, Italy.

[[]Presentation title: Safety and Efficacy of Ticlopidine and Aspirin Combination Versus Aspirin Alone in the Secondary Prevention of Stroke. Abstract 7[]]