Secondary Stroke Prevention with ASA plus Dipyridamole - Good for the Brain, but Bad for the Heart?
In contrast to ASA plus clopidogrel being indicated and often prescribed for treatment of coronary heart disease, intravenous dipyridamole is used in cardiology to induce myocardial ischaemia in stress tests.
Data from clinical studies of stroke patients don't suggest an increased risk for myocardial ischaemia or other cardiovascular incidents because of orally administration of dipyridamole. However, these data are derived from subgroup analysis of stroke studies, especially from the ESPS 2 study, but not from studies of primary cardiac patients.
Reference:
Darius H. Cardiovasc 2004; 9: 29-32.
Because atherosclerosis isn't organ-specific but a ubiquitary disease, patients who suffered a first atherothrombotic incidence have a significant higher risk to suffer a second one in another part of their vasculature. The epidemiological getABI-study showed a high cross-incidence of CVD, peripheral occlusive arterial disease and CHD.
But neurological secondary prevention-studies like CATS, TASS and ESPS-II showed that the most frequent incidence after a first stroke is a second one, MI follows only in the second instance. Patients of the secondary prevention study CAPRIE, who had suffered a stroke or TIA, suffered a second neurological occurrence in 10% of all cases. Only 1.5% of all these patients suffered a MI as secondary occurence.
Reference:
Darius H. Cardiovasc 2004; 9: 29-32.
Guidelines of the German Association for Neurology (Deutsche Gesellschaft für Neurologie) for the treatment of patients with known CHD who suffered a stroke, recommend ASA or clopidogrel or a combination of 25 mg ASA plus 200mg dipyridamole two times daily.
Reference:
http://www.dgn.org/127.0.html
BACKGROUND & DESIGN
The second European Stroke Prevention Study investigated the prevention of stroke and/or death in 6602 patients with transient ischaemic attack or stroke with aspirin (25 mg b.d.), extended-release dipyridamole (200 mg b.d.), the combination of aspirin and dipyridamole or placebo. This post hoc analysis investigated cardiac events in patients with coronary heart disease or myocardial infarction (MI) at entry. ESPS-2 had a 2 x 2 factorial design. For this analysis all patients who received dipyridamole were compared to those who did not receive dipyridamole. Similarly, all patients who were treated with aspirin wer compared with those who were not treated with aspirin.
Reference:
Diener et al. Int J Clin Pract 2001; 55 (3): 162-163.
 |
|
|
|
|
|
|
| |
Treatment groups |
| |
Aspirin/DP |
DP |
Aspirin |
Placebo |
| CHD |
573 (34.7%) |
598 (36.2%) |
571 (34.6%) |
577 (35.0%) |
| Prior MI |
237 (14.4%) |
214 (12.9%) |
221 (13.4%) |
219 (13.3%) |
| Total |
1650 |
1654 |
1649 |
1649 |
|
|
|
|
|
|
|
|
| |
Treatment groups in the factorial analysis |
| |
DP |
No DP |
Aspirin |
No Aspirin |
Placebo |
| CHD |
1171 (35.4%) |
1148 (34.8%) |
1144 (34.7%) |
1175 (35.6%) |
2319 (35.1%) |
| Prior MI |
458 (13.9%) |
433 (13.1%) |
451 (13.7%) |
440 (13.3%) |
891 (13.5%) |
| Total |
3304 |
3298 |
3299 |
3303 |
6602 |
CHD = coronary heart disease; MI = myocardial infarction; DP = dipyridamole;
aspirin = acetylsalicylic acid
Patients with CHD or prior MI were evenly distributed across the treatment arms. Between 34.7% and 36.2% of the patients suffered from CHD and between 12.9% and 14.4% had had an MI at entry into the trial
Reference:
Diener et al. Int J Clin Pract 2001; 55 (3): 162-163.
|
|
|
|
|
|
|
|
|
| Mi |
Dipyridamole |
No Dipyridamole |
Total |
Aspirin |
No Aspirin |
Total |
| Yes |
83 (2.5%) |
84 (2.5%) |
167 |
74 (2.2%) |
93 (2.8%) |
167 |
| No |
3221 (97.5%) |
3214 (97.5%) |
6435 |
3225 (97.8%) |
3210 (97.2%) |
6435 |
| Total |
3304 |
3298 |
6602 |
3299 |
3303 |
6602 |
| chi² test: p = 0.928 |
chi² test: p = 0.139 |
In the two-year observation period 167 new Mis occurred: 83 in patients on dipyridamole and 84 in patients not on dipyridamole. There was a trend for fewer Mis in patients who were on aspirin than in those who were not on aspirin (74 vs 93, respectively). Numbers were to small to achieve significance in statistical testing.
Reference:
Diener et al. Int J Clin Pract 2001; 55 (3): 162-163.
|
|
|
|
|
|
|
|
|
| Mortality |
Di-
pyridamole |
No Di-
pyridamole |
Total |
Aspirin |
No Aspirin |
Total |
| Yes |
83(2.5%) |
84(2.5%) |
167 |
74 (2.2%) |
93 (2.8%) |
167 |
| No |
3221 (97.5%) |
3214 (97.5%) |
6435 |
3225 (97.8%) |
3210 (7.2%) |
6435 |
| Total |
3304 |
3298 |
6602 |
3299 |
3303 |
6602 |
| chi² test: p = 0.652 |
chi² test: p = 0.344 |
Altogether 761 patients died during the two-year observation period. There was no difference in all-cause mortality in patients who received dipyridamole (375) compared with those who did not (386). The same was true for patients on aspirin (386) or not (393). Mortality was identical in patients with CHD or prior MI irrespective of wether they took dipyridamole (213) or not (208) or aspirin (209) or not (212).
CONCLUSION
Dipyridamole did not result in a higher number of cardiac events, e.g. angina pectoris, MI, or death from all causes. The combination of aspirin plus dipyridamole was superior to either drug alone in the prevention of stroke.
PubMed Abstract
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References:
Diener et al. Int J Clin Pract 2001; 55 (3): 162-163. |
