Trials Flashcards
Endarterectomy for asymptomatic carotid artery stenosis.
- Pts (typically white, male) w/ 60% or more asx extracranial CAS who have CEA done w/ <3% periop mortality will have a 6% ARR in stroke/death compared to those who only receive ASA over 5 years.
- Primary endpt: Initially TIA, stroke in dist of culprit artery, or periop death (TIA later removed)
- NNT to prevent 1 stroke over 5 years was 19
ACAS
JAMA 1995
10-year stroke prevention after successful CEA for asx stenosis.
- In pts age < 75, CEA for asx 60-90% cervical ICA stenosis significantly reduced 10 year stroke risk compared to not getting CEA.
- CEA performed at median delay 1 month.
- Primary outcome: Periop mortality/morbidity and non-periop stroke favoring CEA group.
- 5-year stroke risk: 6.9% CEA vs 10.9% no CEA (including periop events)
- 10-year stroke risk: 13.84% CEA vs 17.9% no CEA (incl periop)
- Pts >75 years didn’t seem to benefit
- Sig reduction in ipsilateral, contralateral, and VB territory strokes
- No difference in subgroup analyses by sex, degree of stenosis
ACST-1
Lancet 2010
Effect of clopidogrel added to ASA in pts with afib.
- In pts not suitable for warfarin, ASA + clopidogrel significantly decreased ischemic stroke risk and significantly increases minor and major bleeding compared to ASA monotherapy.
- Primary outcome: Any major vascular event or death.
- ASA 75-100 + Plavix 75: 6.8% events/year
- ASA monotherapy: 7.6% events/year
- RR 0.89
- DAPT reduced risk of any stroke (RR 0.72) and ischemic stroke (1.9% vs 2.8%, RR 0.68)
- DAPT: hemorrhagic stroke nonsignifcantly increased; bleeding of any type (except fatal) all significantly increased; Major: RR 1.57, 1.3% vs 2.0%; Minor: RR 1.87, 0.2% vs 0.4%; GI: RR 1.96, 0.5% vs 1.1%; ICH (RR 1.87, 0.2% vs 0.4%
ACTIVE-A
NEJM 2009
Clopidogrel + ASA vs oral AC for afib
- Warfarin is superior to ASA+Plavix (75-100 + 75) for preventing vascular complications inpatients with afib
- Primary: First occurrence of major vascular event
- Annual risk: Warfarin 3.93% vs DAPT 5.68%
- Non-disabling strokes sig decreased with warfarin, but disabling and fatal strokes were not.
- Hemorrhagic stroke significantly increased with warfarin (0.36%) vs DAPT (0.12%) with p=0.036
- No sig difference in bleeding complications
- Study stopped early because of clear benefit of warfarin over DAPT
ACTIVE-W
Lancet 2006
Clopidogrel + ASA vs warfarin in patients with stroke and aortic arch plaques
- In pts with thoracic aortic plaque > 4mm
- No conclusion, trial underpowered and stopped early (funding)
- DAPT had fewer events compared to warfarin, but did not reach statistical significance
- Primary endpoint: Cerebral infarct, MI, peripheral embolism, vascular death, intracranial hemorrhage
- Followed for median of 3.4 years
ARCH
Stroke 2014
Effectiveness and safety of oral ACs among nonvalvular afib pts
- All DOACs have a lower risk of stroke/systemic embolism compared to warfarin (apixaban HR 0.61; dabigatran HR 0.80; rivaroxaban HR 0.80); only apixaban and dabigatran have lower rates of major bleeding
- All DOACs had lower rates of hemorrhagic strokes compared to warfarin, only apixaban and rivaroxaban had lower rates of ischemic stroke
- Rivaroxaban had higher rate of major bleeding compared to warfarin
- Apixaban superior to rivaroxaban and dabigatran for stroke/systemic embolism and major bleeding
- Limited 2/2 being retrospective observational
ARISTOPHANES
Stroke 2018
Apixaban vs warfarin in patients with a fib
- Apixaban 5 mg BID superior to warfarin INR 2-3 for prevention of stroke and systemic embolism in patients with afib (1.27% vs 1.6% events/year, HR 0.79; p < .001 for noninferiority, p = 0.01 for superiority), and sig less ICH (0.33% vs 0.8%), major bleeding (2.13% vs 3.09%, HR 0.69), and death (3.52% vs 3.94%, HR 0.89)
- Primary outcome: Stroke or systemic embolism, followed median 1.8 yrs
ARISTOTLE
NEJM 2011
Antihypertensive treatment of acute cerebral hemorrhage
- Pts with supratentorial ICH 60 cc or less can be treated with nicardipine to a goal of 3 SBP tiers within 6 hours of symptoms onset: 170-200, 140-170, 110-140 safely.
Increase in SAEs, death, and tx failure with greater SBP reduction goal but not beyond specified study thresholds
- Primary: feasibility, neurological worsening w/in 24 hours, SAEs w/in 72 hours
- low power
- all bleeds thought to be due to HTN (may not extrapolate to other causes)
ATACH
Crit Care Med 2010
Intensive BP lowering in pts with acute cerebral hemorrhage
- Rish of death or disability at 3 m did not differ between intensive (goal 110-139) vs standard (goal 140-179) SBP lowering within 4.5 hours of symptom onset
- Higher rate of adverse renal events within 7 days of tx in the intensive group
- Study stopped early for futility
- SAE related to tx was higher in intensive group at 3 months (25.6% vs 20%, p=0.05
- Mean ICH volume 10cc
- Mean SBP 2 hours after randomization was 129 (intensive) vs 141 (standard)
ATACH-2
NEJM 2016
Results for patients treated within 3 hours of stroke onset.
Alteplase thrombolysis for acute noninterventional therapy in ischemic stroke
- Pts with acute ischemic stroke treated with IV tPA within 3 hours of LKW had a significantly greater likelihood of achieving an NIHSS of 0-1 at 90 days compared to placebo, with a significantly increased risk of sICH (13% vs 0%)
- Results limited by small sample size (n=61)
- No sig difference in functional outcome scores (Barthel, mRS, GOS)
- Later subgroup analysis showed that earlier treatment within the 3 hour window resulted in even better functional outcomes
ATLANTIS
Stroke 2002
Efficacy and safety of very early mobilization within 24 hours of stroke onset
- Less likely to result in an mRS of 0-2 at 3 months compared to usual care alone (46% vs 50%, OR 0.73, p=0.004)
- No sig difference in mortality or nonfatal AE
AVERT
Lancet 2015
Bleeding risk analysis in stroke imaging before thrombolysis - pooled analysis of T2*-weighted MRI data
- In pts with CMBs (typically 5 or less in #) no significant increased risk of sICH when given tPA within the first 6 hours of sx onset compared to pts who do not have CMB
- Primary end pt: rate of sICH in pts with and w/o CMBs, defined as NIHSS worsening of 4 pts or greater
- sICH rate 5.8% in presence of CMBs vs 2.7% in pts without (p=0.170)
BRASIL
Stroke 2007
Perioperative bridging AC in pts with a fib
- in pts with afib on warfarin undergoing elective surgery, bridging with LMWH periop had a significant increase in major bleeding and no significant increase in arterial thromboembolism compared to placebo
- major bleeding 1.3% no bridging vs 3.2% bridging (RR 0.41, p=0.005)
- pts who may be considered higher risk for recurrent stroke were not well represented
- mean CHADS2 score was 2.3
BRIDGE
NEJM 2015
Antiplatelet tx compared with AC tx for cervical artery dissection
- In pts with extracranial carotid or vert dissection randomized withing 7 days of TIA or stroke, no sig difference in ipsilateral stroke or death within 3 months (2% antiplt vs 1% AC, p=0.63)
(20% of pts had no dissection when imaging was centrally adjudicated)
- drug choice was open label for both (for AC, no DOACs used)
CADISS
Lancet Neurology
A randomized blinded trial of clopidogrel vs aspirin in pts at risk of ischemic events
- clopidogrel showed slightly reduced vascular complication rates compared to ASA, driven mostly by reductions in the rate of vascular complications in PAD pts
- Primary outcome: composite cluster of ischemic storke, MI, or vascular death
- mean time to randomization to ischemic stroke subgroup was 53 days
CAPRIE
Lancet 1996
