JOURNAL OF THE
NEUROLOGICAL
ELSEVIER Journal of the Neurological Sciences 151 (1997) S61
10. Conclusions
ESPS 2 was a multicentre, double-blind, placebo-
controlled trial, in which 6602 patients were investi-
gated for secondary prevention of stroke, death and
stroke and/or death by low-dose ASA and/or modi-
fied release DP. Therapy with ASA alone and DP
alone were significantly effective in preventing stroke
(risk reductions 18.1% and 16.3%, respectively). Com-
bined treatment with DP-ASA was more effective
than treatment with either drug alone (risk reduction
= 37.0%). Factorial design analysis showed that ASA
and DP act additively on stroke prevention. While the
results seen in ESPS 2 with this low dose of ASA
confirm those reported in the literature at higher
dose, the statistically significant effect of DP alone is
a new element in the field of secondary stroke preven-
tion, since dipyridamole 400 mg daily is shown here to
be as effective as ASA when given alone. Thus, DP is
an effective alternative in patients who are intolerant
of ASA. Secondly, the combination of DP and ASA is
more effective than either drug alone, thus raising the
standard for effective stroke prevention.
ASA and/or DP did not reduce significantly death
from any cause. In this respect, ESPS 2 is also in
accordance with previously published studies, apart
from ESPS 1, which did report a mortality benefit in
patients treated with DP-ASA.
ESPS 2 is the first stroke prevention trial in which
antiplatelet treatment has been shown to be effective
in preventing TIA, considered as an individual out-
come, in a very similar way as in preventing stroke. As
with stroke, both ASA and DP were effective when
SCIENCES
given alone, and the combination effect of both drugs,
when given together, was additive. ASA and/or DP
showed evidence of effect in preventing deep venous
thrombosis and peripheral arterial occlusion, events
which were recorded together as other vascular events.
Systematic enquiring at each patient follow-up visit
demonstrated that headache and gastro-intestinal
complaints were more common in the DP groups
leading to 7% more treatment cessations early in the
study, while bleeding was more commonly reported in
both ASA groups. While efficacy of the DP-ASA
combination was superior to that of ASA alone or DP
alone, the overall incidence and severity of side ef-
fects were not increased in the DP-ASA group. In this
respect, the DP-ASA efficacy/safety profile provides
an advantage over that of either drug alone.
In conclusion, ESPS 2 is characterized by successful
patient recruitment, a balance between treatment
groups, a relatively high proportion of major strokes
as qualifying event, and a very clear result in terms of
stroke and TIA prevention. TIA is in addition a risk
factor for future stroke. Consequently, the conclu-
sions of ESPS 2 as to the value of low-dose ASA, DP
and their co-administration in the secondary preven-
tion of stroke and TIA provides a new standard in
clinical management. Optimal secondary preventive
treatment for stroke and/or TIA therefore appears to
be the combination treatment of ASA + DP (Asasan-
tin@ Retard) with the fallback position of using one of
the two in case of intolerance of the other.