#18: Warfarin and aspirin in patients with heart failure and sinus rhythm
- Heart failure, even without AF increases stroke risk: it leads to a hypercoagulable state and promotes formation of LV thrombus
- Previous studies were underpowered to find a difference between warfarin and aspirin therapy
- This study was a double-blind, aspirin to warfarin head to head comparison in patients with EF < 35% but without other indications for anticoagulation (or aspirin)
- Unfortunately, this study also had difficulty with recruitment. They had to extend the follow up period from 5 to 6 years to increase power, and even so it was than hoped (original target sample size was 2860 patients, for 89% power to test the primary hypothesis; the final sample of 2305 patients gave the study 69% power)
- Heart failure is rough: 27% of patients had the primary outcome of combined ischemic stroke, ICH or death.
- No statistical difference between the two groups overall; at 4 years, there was a very slightly significant benefit from warfarin
- The warfarin group actually did have benefit from a stroke prevention perspective (hazard ratio 0.52), similar to patients in AF, but because the stroke rate is lower, the benefit was less, and was outweighed by increased risk of major bleeding
- Interestingly, there wasn’t a difference in ICH
Conclusion: no clear benefit, decision should be individualized etc. Based on this I would probably just stick to aspirin.
#17: Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor prognosis
- This article is from 2004. I guess the merits of permissive hypertension was less settled then? They do suggest that hypertension could facilitate the development of edema in infarcted tissue so it kind of makes sense why people would be reluctant.
- This paper followed 304 consecutive patients with hemispheric ischemic stroke who presented within 24 hours
- Once in the stroke unit, patients were only treated for BP > 220/120, but a bunch of them already got meds in the ED, because, it’s the ED basically
- Blood pressure on admission was not related to early neurologic deterioration or outcome at 3 months, but with some fancier statistics they managed to tease out a U-shaped curve: patients with SBP around 180 had the best outcomes
- BP tended to decrease on its own within the first day
- Reductions in SBP or DBP > 20mmHg were associated with increased infarct volume and overall worse outcomes
Bottom line, I guess, is that super high blood pressure may be a marker of poor prognosis, but treating it is also harmful.
#16: Remote or extraischemic ICH–an uncommon complication of stroke thrombolysis
- This paper goes into the ECASS classification of hemorrhage after tPA: basically 4 classifications for hemorrhage within the infarct, vs remote parenchymal hemorrhage (PHr)
- In patients given thrombolytics for acute MI, the rate of ICH is 0.3-0.8%, but in stroke patients, the hemorrhage rate in NON-infarcted brain is still 1.3-3.7%, several times higher.
- This paper looked at data from 43k patients from the SITS-ISTR, an international stroke thrombolysis registry
- Of all the post-tPA hemorrhage, about 1/3 was remote from the infarct (2.2% vs 5.3% within the infarct)
- The way they did this analysis is a little goofy (they compared hemorrhagic infarct vs remote hemorrhage), but compared to those patients who had hemorrhage infarcts, the patients with remote hemorrhage were a little older, more female, and were more likely to have had a prior stroke. The paper goes on to say that maybe this is because the older ladies have amyloid angiopathy which makes them more likely to bleed.
So, interesting paper. The only thing is I’ve read it a couple times now and I still think the statistics are backwards compared to what would be clinically useful, like which patients should I be the most concerned about hemorrhage after tPA? And from reading this I’m not clear if that’s the elderly ladies or not.
#15: Reducing in-hospital delay to 20 minutes in stroke thrombolysis
Based on data from the Helsinki stroke registry, this paper described interventions that collectively allowed a stroke center to reduce their door-to-treatment time to 28 minutes, with half of patients treated within 20 minutes! Some of the key interventions included:
- EMS calls the ED stroke physician’s mobile phone directly
- All orders are done and tPA is premixed while the patient is still in transport
- Accucheck is done by the paramedics, and a POC INR done on arrival; they don’t necessarily wait for other labs
- When the patient gets to the ED, they are transferred immediately onto the CT table (which is located in the ED) instead of an ER gurney. The stroke team is there, and the tPA bolus is given while they’re still on the table
Cool, right? I feel like there is SO MUCH INEFFICIENCY in medicine, and it’s nice to see that sometimes little things, like skipping the ED bed step, can collectively make a big difference.
Now that we’re finally through the guidelines, we’ll be taking a look at some more of the evidence for acute stroke.
#14: Time to treatment with IV tPA and outcome from acute ischemic stroke
- In acute stroke, the volume of irreversibly injured tissue expands quickly: estimated loss of 2 million neurons per minute!
- The combined tPA trials only included 1850 patients, not really enough to show a clear effect from time to treatment
- This study used 10 years of data from a nationwide registry, the AHA/ASA Get With The Guidelines–Stroke registry, which after exclusion for a variety of factors, still had 58k patients’ worth of data to analyse
- The median time to treatment was 144 minutes
- More rapid administration of tPA was associated with essentially all outcomes: reduced mortality, fewer symptomatic ICHs, and more frequent discharge home vs death or to an institution
- When tPA was given within 90 minutes, patients were 26% less likely to die, and 50% more likely to be ambulatory at discharge vs those who got it between 3-4.5 hours
So, I mean, I think we kind of already knew this, even if not 100%…I was a little surprised when I realized the paper was published in 2013. But more evidence is always good, right? PS is it just me or is database analysis the route to getting papers published quickly? I mean, obviously it’s a lot of work, but…compared to running gels in a lab, or whatever they do? Making a mental note to learn more stats.
Wrapping up our whirlwind tour of the guidelines!
Section 4: Other treatment ideas and supportive stroke care
- Hemodilution and vasodilators don’t seem to work. A very selected subset of patients may benefit from pressors. Hypothermia had mixed results.
- Albumin may have a positive impact, definitive results pending.
- Nimodipine works in SAH but not in ischemic stroke; the neuroprotective effect likely outweighed by BP lowering.
- The combination of caffeine and alcohol seemed relatively safe in a pilot study!
- For patients already on statins, interrupting therapy even briefly was associated with worse outcomes.
- Specialized stroke outcomes are key: the benefits persist for years, with an effect comparable to administration of tPA. The number needed to treat for a CSC to prevent 1 death or institutional care at 1 year was only 29.
- Healthcare providers can safely do a bedside swallow eval; a “wet voice” after swallowing is a good predictor of aspiration.
- PREVAIL study showed lovenox is better than BID heparin for DVT prevention in ischemic stroke.
- 25% of strokes will deteriorate within 1-2 days: 1/3 because of stroke progression, 1/3 because of swelling, and the remaining third equally split between hemorrhage and recurrent stroke.
- The benefit for decompressive surgery is only shown for patients younger than 60.
And that’s all, folks. Normal length articles return next week.
Continuing with the stroke guidelines…earlier posts here and here.
Section 3: Endovascular interventions through antiplatelet agents
- Intra-arterial tPA is actually not well studied. The evidence for intra-arterial thrombolysis is a couple trials with urokinase.
- Both the Solitaire and the Trevo, stent retrieval devices, outperformed Merci in head-to-head trials
- Immediate anticoagulation (like for NSTEMIs) hasn’t shown any net benefit
- Even the evidence of immediate aspirin is kind of weak: two trials individually had a non-significant effect on death/disability when started within 48 hours, but when combined, there was a modest effect, likely attributable to a reduction of early recurrent stroke
- Plavix takes at least 5 days for full effect when started at 75mg daily
- Aspirin comes in an IV formulation! But adding it to tPA worsened outcomes.