45 research outputs found
Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
Background
Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared
the efficacy and safety of two antiplatelet regimens â aspirin plus extendedrelease
dipyridamole (ASAâERDP) versus clopidogrel.
Methods
In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive
25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive
75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke.
The secondary outcome was a composite of stroke, myocardial infarction, or death
from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075),
followed by superiority testing, was planned.
Results
A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke
occurred in 916 patients (9.0%) receiving ASAâERDP and in 898 patients (8.8%) receiving
clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The
secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for
ASAâERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events
among ASAâERDP recipients (419 [4.1%]) than among clopidogrel recipients (365
[3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage
(hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major
hemorrhagic event was similar in the two groups (1194 ASAâERDP recipients [11.7%],
vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).
Conclusions
The trial did not meet the predefined criteria for noninferiority but showed similar rates
of recurrent stroke with ASAâERDP and with clopidogrel. There is no evidence that either
of the two treatments was superior to the other in the prevention of recurrent
stroke. (ClinicalTrials.gov number, NCT00153062.
Validity constraints for data analysis workflows
\ua9 2024Porting a scientific data analysis workflow (DAW) to a cluster infrastructure, a new software stack, or even only a new dataset with some notably different properties is often challenging. Despite the structured definition of the steps (tasks) and their interdependencies during a complex data analysis in the DAW specification, relevant assumptions may remain unspecified and implicit. Such hidden assumptions often lead to crashing tasks without a reasonable error message, poor performance in general, non-terminating executions, or silent wrong results of the DAW, to name only a few possible consequences. Searching for the causes of such errors and drawbacks in a distributed compute cluster managed by a complex infrastructure stack, where DAWs for large datasets typically are executed, can be tedious and time-consuming. We propose validity constraints (VCs) as a new concept for DAW languages to alleviate this situation. A VC is a constraint specifying logical conditions that must be fulfilled at certain times for DAW executions to be valid. When defined together with a DAW, VCs help to improve the portability, adaptability, and reusability of DAWs by making implicit assumptions explicit. Once specified, VCs can be controlled automatically by the DAW infrastructure, and violations can lead to meaningful error messages and graceful behavior (e.g., termination or invocation of repair mechanisms). We provide a broad list of possible VCs, classify them along multiple dimensions, and compare them to similar concepts one can find in related fields. We also provide a proof-of-concept implementation for the workflow system Nextflow
Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
Background
Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared
the efficacy and safety of two antiplatelet regimens â aspirin plus extendedrelease
dipyridamole (ASAâERDP) versus clopidogrel.
Methods
In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive
25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive
75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke.
The secondary outcome was a composite of stroke, myocardial infarction, or death
from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075),
followed by superiority testing, was planned.
Results
A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke
occurred in 916 patients (9.0%) receiving ASAâERDP and in 898 patients (8.8%) receiving
clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The
secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for
ASAâERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events
among ASAâERDP recipients (419 [4.1%]) than among clopidogrel recipients (365
[3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage
(hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major
hemorrhagic event was similar in the two groups (1194 ASAâERDP recipients [11.7%],
vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).
Conclusions
The trial did not meet the predefined criteria for noninferiority but showed similar rates
of recurrent stroke with ASAâERDP and with clopidogrel. There is no evidence that either
of the two treatments was superior to the other in the prevention of recurrent
stroke. (ClinicalTrials.gov number, NCT00153062.
Telmisartan to prevent recurrent stroke and cardiovascular events
Background
Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent
stroke. In addition, inhibition of the reninâangiotensin system in high-risk patients
reduces the rate of subsequent cardiovascular events, including stroke. However, the
effect of lowering of blood pressure with a reninâangiotensin system inhibitor soon
after a stroke has not been clearly established. We evaluated the effects of therapy
with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.
Methods
In a multicenter trial involving 20,332 patients who recently had an ischemic stroke,
we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive
placebo. The primary outcome was recurrent stroke. Secondary outcomes were
major cardiovascular events (death from cardiovascular causes, recurrent stroke,
myocardial infarction, or new or worsening heart failure) and new-onset diabetes.
Results
The median interval from stroke to randomization was 15 days. During a mean followup
of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan
group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group
and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in
the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P = 0.23). Major
cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and
1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01;
P = 0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the
placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P = 0.10).
Conclusions
Therapy with telmisartan initiated soon after an ischemic stroke and continued for
2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular
events, or diabetes. (ClinicalTrials.gov number, NCT00153062.