PRoFESS®
- is one of the world’s largest trials in prevention of recurrent stroke with 20,332 patients enroled
- is the first head-to-head comparison of antiplatelet treatment for recurrent stroke prevention (ER-dipyridamole + ASA or clopidogrel)
- compares telmisartan vs. placebo on top of antiplatelet therapy
- uses a 2 x 2 factorial trial design that allows assessment of the contribution of each treatment tested
- is a multinational trial with substantial representation of all continents and races
- succeeded to enrol more than 2/3 of patients within 30 days of stroke onset
- has enroled a wide spectrum of patients with different ischaemic stroke subtypes (small vessel as well as large artery disease) and stroke severity (modified Rankin Scale 0–5)
- nearly 1/3 of patients were diabetic and more than 2/3 were hypertensive
- patients receive state of the art cardiovascular treatment (statin use in 47% of patients, BP well controlled at baseline with a mean BP of 144/84 mmHg)
PRoFESS®
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| Study design: |
- Randomised, double-blind, placebo-controlled multicentre study
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| Population: |
- 20,332 stroke patients
- 695 stroke units in 35 countries
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| Treatment: |
- Aggrenox® vs. clopidogrel
- The second study arm tested telmisartan versus placebo in addition to Aggrenox® or clopidogrel
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| Early treatment with Aggrenox®: |
- 40 % within the first 10 days
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| Treatment period: |
- 1.5 up to 4-4 years (median:2.5 years)
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| Primary outcome: |
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| Secondary outcome: |
- Stroke, myocardial infarction or vascular death
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PRoFESS®: A global study that gives global insights into a representative patient population (20,332 patients)
PRoFESS® directly compares Aggrenox® and clopidogrel in secondary stroke prevention
PubMed Abstract
Reference:
Diener, Sacco, Yusuf. Cerebrovasc Dis 2007; 23: 368–380
Primary outcomeFirst recurrence of stroke was confirmed in 1814 patients.
In 916 recipients (9.0%) treated with aspirin plus extended-release dipyridamole
and 898 recipients (8.8%) treated with clopidogrel, a first recurrent stroke occurred
(hazard ratio, 1.01; 95% CI, 0.92 to 1.11).
The results for the primary outcome had a hazard ratio very close to 1.00
(representing equivalence). However, the upper limit of the confidence
interval extended beyond the non-inferiority margin of 1.075.
Aggrenox® did not meet the predefined statistical non-inferiority. The data suggest, that
Aggrenox® shows comparable rates in recurrent stroke prevention as clopidogrel.
PubMed Abstract
Reference:
Sacco RL, Diener HC, Yusuf S et al. N Engl J Med 2008; 359.
Aggrenox® did not meet the predefined statistical non-inferiority versus clopidogrel. The composite endpoint is not part of the current label of Aggrenox® / Asasantin®.
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ER-DP +ASA |
Clopidogrel |
HR (ER-DP+ASA) |
95% CI |
| Number of randomised patients |
10,181 |
10,151 |
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| MI |
178 (1.7%) |
197 (1.9%) |
0.90 |
0.73, 1.10 |
| New/worsening CHF |
144 (1.4%) |
182 (1.8%) |
0.78 |
0.62, 0.96 |
| Death |
739 (7.3%) |
756 (7.4%) |
0.97 |
0.87, 1.07 |
| Other designated vascular events |
533 (5.2%) |
517 (5.1%) |
1.03 |
0.91, 1.16 |
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| Sacco RL, Diener HC, Yusuf S et al. N Engl J Med 2008; 359. |
Secondary and Tertiary outcomes
- The occurrence of the secondary outcome (stroke, myocardial infarction,
or death from vascular causes) was with 1333 patients (13.1%) (hazard
ratio for extended-release dipyridamole plus aspirin vs. clopidogrel, 0.99;
95% CI, 0.92 to 1.07) identical for extended-release dipyridamole plus
aspirin and clopidogrel.
- The rates of most tertiary (efficacy) outcomes were similar in the two
groups.
- A significantly lower incidence of new or worsening congestive heart
failure was found in patients treated with extended-release dipyridamole
plus aspirin (144 patients [1.4%]) than in patients receiving clopidogrel
(182 patients [1.8%]; hazard ratio, 0.78; 95% CI, 0.62 to 0.96).
- The occurrence of recurrent stroke or major haemorrhagic events did not differ significantly in patients receiving extended-release
dipyridamole plus aspirin (1194 [11.7%]) or clopidogrel (1156 [11.4%];
hazard ratio, 1.03; 95% CI, 0.95 to 1.11).
Recurrent ischaemic strokes (the most common event after stroke) were
numerically less frequent in the Aggrenox® group (7.7 % vs. 7.9 %, statistically not
significant), while haemorrhagic strokes were more common (0.9 % vs. 0.5 %, p<0.01).
- No differences in regard of secondary outcome or major haemorrhage
were found between the extended release dipyridamole plus aspirin
group and the clopidogrel group in post hoc analysis: 1572 patients
[15.4%] events for the extended release dipyridamole plus
aspirin and 1563 patients [15.4%] for the clopidogrel group; hazard ratio,
1.00; 95% CI, 0.93 to 1.07).
PubMed Abstract
Reference:
Sacco RL, Diener HC, Yusuf S et al. N Engl J Med 2008; 359.
- PRoFESS® was not able to meet the pre-specified non-inferiority criteria for ER-DP + ASA vs. clopidogrel
- ER-DP + ASA and clopidogrel had similar rates of recurrent stroke and major vascular events
- The composite outcome of stroke, MI or vascular death rates were identical in the two groups
- The major haemorrhagic complication rates were not significantly different between ER-DP + ASA and clopidogrel.
Recurrent ischaemic strokes (the most common event after stroke) were
numerically less frequent in the Aggrenox® group (7.7 % vs. 7.9 %, statistically not
significant), while haemorrhagic strokes were more common (0.9 % vs. 0.5 %, p<0.01).
- There was no significant difference in the risk of fatal or disabling
stroke
- Net benefit/ risks were similar in the 2 agents defined as the combination of recurrent stroke and major haemorrhage
If you would like to learn more about PRoFESS® and the results of this study or Aggrenox® in general please follow the link to the new Aggrenox® Slide Kit or the link to the homepage of the New England Journal of Medicine for the online publication & the editorial: (Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke)
PubMed Abstract
Reference:
Sacco RL, Diener HC, Yusuf S et al. N Engl J Med 2008; 359.
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