MD Conference Express ISC 2012 - (Page 20)
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C L I N I C A L
T R I A L
H I G H L I G H T S
Probability of Death
2 x 2 factorial design to antiplatelet therapy—325 mg aspirin daily plus 75 mg clopidogrel daily versus 325 mg aspirin daily plus placebo—and to one of two levels of open-label blood pressure targets—intensive (130 mm Hg) versus usual (130 to 149 mm Hg). Exclusion criteria included cortical stroke, cardioembolic disease, or carotid stenosis. SPS3 was a superiority trial that was powered to detect a clinically significant difference in outcomes. The primary outcome was time to recurrent stroke (ischemic or hemorrhagic), analyzed separately for each intervention. The secondary outcomes were rates of cognitive decline and major vascular events. Mean time from index event to randomization was 76 days. Mean follow-up was 3.5 years. Loss to follow-up was 2%. The primary and secondary outcomes were centrally, blindly adjudicated. Baseline characteristics of patients were similar in both groups, with a mean Mini Mental State Exam score of 28± 2.3. In the aspirin group (n=1503), 66% had a Rankin score of 0 to 1; the figure in the aspirin+clopidogrel group (n=1517) was 67%. The race/ethnicity of participants was 52% white, 31% Hispanic, and 17% black. Baseline medical characteristics, clinical syndromes, and percentage from each region (North America, Latin America, and Spain) were all similar. The probability of the primary event over time showed no difference between the two groups: aspirin=138 (2.7%/ patient-year) compared with aspirin+clopidogrel (n=126; 2.5%/patient-year; HR, 0.92; 0.73 to 1.2; p=0.52). The incidence of ischemic stroke was also nonsignificant: aspirin group (n=125; 2.4%/patient-year) compared with aspirin+clopidogrel (n=105; 2.1%/patient-year; HR, 0.85; 0.66 to 1.1; p=0.21). Major vascular events (stroke, myocardial infarction, or vascular death) were also not significantly different. Differences in all-cause mortality were significantly different: aspirin (n=77; 1.4%/patient-year) and aspirin +clopidogrel (n=113; 2.1%/patient-year; HR, 1.5; 1.1 to 2.0p=0.005; Figure 1). Differences in probable vascular events (p=0.012), all hemorrhages (p<0.001), and non-CNS hemorrhages were also significant (p<0.001; Table 1). The antiplatelet intervention was stopped prematurely in July 2011 for reasons of safety and futility. The authors concluded that dual antiplatelet therapy was not more efficacious than aspirin alone. Major bleeds and total mortality were increased. The results do not support the use of combination therapy for stroke prevention in patients with lacunar strokes.
Figure 1. All-Cause Mortality.
0.5 Aspirin=77 (1.4%/pt-yr) Aspirin+Clopidogrel=133 (2.1%/pt-yr) HR 1.5 (1.1 to 2.0) p=0.005
0.4
0.3 Group 1: Aspirin+Clopidogrel
0.2
0.1 Group 2: Aspirin+Placebo 0 0 1
1312 1339
2
1087 1087
3
647 863
4 5 Time (Years)
623 648 390 420
6
211 237
7
98 106
8
3 5
Group 1: Group 2:
1517 1503
Reproduced with permission from OR Benavente, MD, FRCP(C).
Table 1. Major Hemorrhages.
Aspirin n All hemorrhages CNS hemorrhages intercerebral* Subdural† Other‡ Non-CNS hemorrhages 56 15 7 6 3 42 %/pt-yr 1.10 0.28 0.13 0.11 0.005 0.79 Aspirin+ Clopidogrel n 105 22 13 6 2 87 %/pt-yr 2.10 0.42 0.25 0.11 0.038 1.70 2.0 (1.40-2.70) 1.5 (0.79-2.90) 1.9 (0.75-4.70) 1.0 (0.33-3.20) 0.7 (0.12-4.20) 2.2 (1.50-3.10) <0.001 0.21 0.18 0.95 0.70 <0.001 HR (95% CI) p value
*Intraparenchymal, spinal; †Subdural, epidural; ‡Subarachnoid, other.
Novel Agent NA-1 Proves that Ischemic Neuroprotection is Possible in Older Patients
Written by Rita Buckley
The Evaluating Neuroprotection in Aneurysm Coiling Therapy trial [ENACT; NCT00728182] showed that the novel agent NA-1 may be a useful treatment for stroke and ruptured aneurysm patients. Michael D. Hill, MD, MSc, FRCPC, University of Calgary, Calgary, Alberta, Canada, reported outcomes from the study. A randomized, multicenter, double-blind, placebo-controlled, single-dose Phase 2 trial, ENACT randomized 197 male and
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April 2012
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Table of Contents for the Digital Edition of MD Conference Express ISC 2012
MD Conference Express ISC 2012
From Neurovascular Laboratory to Clinic: A Journey Through Time
No Compelling Evidence to Use Warfarin or Aspirin in Heart Failure Patients
AXIS 2 Clinical Outcomes No Different Than Placebo
SAMMPRIS: 30-Day Outcomes After Angioplasty and Stenting
Aggressive Medical Therapy Benefits Those Who Fail Antithrombotic Therapy
Initial Clinical Results with TREVO® Mechanical Thrombectomy Device are Promising
Linking sICH Definitions to Outcomes
Solitaire™ Flow Restoration Device Achieves Successful Recanalization Free of Symptomatic Hemorrhage Transformation
FIA II Seeks Genetic Underpinnings of Familial Intracranial Aneurysm
SPS3 Study Does Not Support the Use of Combination Therapy for Stroke Prevention
Novel Agent NA-1 Proves that Ischemic Neuroprotection is Possible in Older Patients
Acute Endovascular Treatment
Neuroimaging
Stroke Guidelines: Current Recommendations in Principle and Practice
The Rising Trend of Ischemic Stroke in the Young
Advanced Neuroimaging Adds Time, Reduces Endovascular Treatment in Clinical Practice
MD Conference Express ISC 2012
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