An algorithm for starting oral anticoagulants after stroke

Once you identified the heart as the emboligenic source of your stroke unit patient’s stroke, the question arises of why, when and how you institute anticoagulation. This hasn’t gotten any easier with all the new drug options, Big Pharma push and the resulting trust we are supposed have in DOACs.

In this short blog entry, I will list my 6-step program for starting oral anticoagulants after an ischemic event. Thanks to the great acronym creator, here is the mnemonic for it: SHuTOFF DOAC.

  • Stroke risk
  • Hemorrhage risk
  • Timing
  • Oral agents
  • Formulary
  • Follow-up

Stroke risk

Calculate the risk of recurrent stroke, if you find data.

  • Atrial fibrillation: 12% vs 1-3%/a under OAC, use a CHADSVASC-calculator for individualized data, bearing in mind that most of the underlying studies were in a primary prevention setting.
  • Atrial thrombus: An atrial thrombus is essentially just a sign of (possibly undetected) afib and insufficient anticoagulation, although it can occur in otherwise bad hearts (see this huge collection of TEE+ pts). Still, we would like to know how more acute the danger of recurrent stroke is, if you find an atrial thrombus on TEE. Or – as increasingly happens – on CTA, when you stumble on a left atrial appendage filling deficit by chance. Does it double or triple? Or stay the same? No proper data found on this. 
  • Ventricular thrombus: Apart from the fact that those are easier to find (TTE suffices) and that ventricular thrombi are due to bad hearts (large MI, severe cardiomyopathy) in general, no data can be found on the rate of acute stroke recurrence in this setting. In the long run (1/2a) it is very impressive (50%) according to very old studies, seemingly lowered by anticoagulation (to 30% in this analysis).
  • Mechanical heart valves: Few studies exist, since everyone thinks these patients absolutely have to be anticoagulated. Only part of the embolic risk is due to the valve itself, the rest comes from afib, especially with mitral valve replacement.
    This 1994 review finds a risk of 4 per 100 pt. years without anticoagulation, reduced to 2,2 by ASS and 1 by VKA. This newer analysis of pts. with St. Jude valves finds similar rates of embolism with OAC.
  • Bioprosthetic heart valves carry a significantly lower risk, about half the number of embolic events seems a good estimate.
  • Low EF: Although we left routine anticoagulation for low EF in primary prophylaxis after the WATCH and WARCEF studies (where a reduction in embolic strokes was offset by the increased bleeding risk for OAC as compared with ASS), a cardioembolic stroke in the setting of severely reduced EF and sinus rhythm should probably trigger oral anticoagulation. I could not find proper data for the stroke risk after an embolic event happened.
  • PFO plus/minus ASA: The risk is extremely low, if no proof of the paradoxical mechanism can be established (no pulmonary embolism, no DVT). Otherwise the risk should be roughly the same as the risk of recurrent venous thrombosis (determined by genetics, mobility, triggers and so on) times the cross-embolism-factor (how many of those embolisms cross over through the PFO, can be measured semiquantitatively in the bubble test, this is my personal invention :-)).

Hemorrhage risk

Risk for spontaneous ICH under OAC

Find and optimize risk factors for hemorrhagic complications under OAC, in particular ICH. For atrial fibrillation there is the simplified  HASBLED-score, but some particular risk factors might benefit from more intensive workup.

  • The A4F complex of the elderly
    • Age
    • Alzheimer’s
    • Apolipoprotein ε2, ε4
    • Amyloid angiopathy
    • Falls
  • Alcohol
  • Altered coagulation (cirrhosis and the like, low platelets)
  • Adherence problems
  • Diabetes
  • Hypertension
  • Interacting medication
    Obviously, the more drugs a patient takes, the higher the risk. With antiplatelet comedication, you double the risk with monotherapy and triple it with dual therapy (or even worse with the newer antiplatelets ticagrelor, cangrelor)
  • Liver and kidney problems
  • MRI markers: leukoaraiosis (no proper gold standard for quantification, may use Fazekas score or volume of white matter hyperintensities, no cutoff established) and number of microbleeds (no proper cutoff because the sensitivity depends on the MRI sequence used and field strength)

Risk for hemorrhagic transformation of the stroke

The acute setting of a stroke raises the obvious concern of bleeding into the stroke (either minor as hemorrhagic transformation or as parenchematous hematoma). Since the detection of hemorrhagic transformation is a matter of the sensitivity of your imaging technique (proportional to the field strength of your scanner, SWI outperforming T2*), only parenchematous hematoma (as can be seen with any old CT or even on ultrasound) should be used to judge the danger of anticoagulation and the reported rates vary between 10 and 30% of cardioembolic strokes. It is unclear, though, whether this rate increases with oral anticoagulation (it does with heparin and LMWH, but those are way more intense) and for how long the danger persists – see next step.

Timing

The 1-3-6-12 rule

There is practically no data on when to start OACs after stroke, so we use the guidelines (ESC 2016) with their practical 1-3-6-12d rule (TIA/NIHSS 0, NIHSS < 8, 8-15, > 15), although they don’t regulate the case of hemorrhagically transformed or parenchymatous hematoma in stroke.

Bridging?

And in the meantime?

  • It is unclear whether ASS makes sense for bridging until OAC in afib – it seems to not hurt much after cardioembolic stroke, though. The guidelines recommend ASS bridging.
  • Heparin or OAC bridging (at least with Warfarin) confers no benefit in the huge studies analyzed in Sandercock’s Cochrane analysis. Whether (lower dosed) DOACs could be used in this setting (analogous to, say, half-hearted LMWH treatment) is also an open question.

Bear in mind that the risk for recurrent stroke during the inpatient period is extremely low (around 3% in simple afib patients – old data, but replicated in modern case series such as this one). It is a daunting question when to bridge in the higher risk groups, such as mechanical heart valves. Most reviews recommend 7-14 days (without proper data to back that recommendation).

Oral anticoagulant

In the next step you have to choose among the 5 options. Consider the acronym DOAC:

  • Drugs: what other drugs is the patient on, what are the possible interactions?
  • Organs: is the patient at risk for renal insufficiency or liver failure?
  • Age: since the lightweight elderly are prone to renal failure even with borderline creatinine, age is a risk factor for all DOACs.
  • Compliance: DOACs aren’t very forgiving, if you forget some doses, VKA usually are.

Formula

Lookup the dose according to all of the above (most of the DOACs have a low and high dose regime, according to risk factors among the above)

Follow-up

Do you have to ensure lab checks? This is obvious and well established for VKAs. It should also be reasonable to check creatinines in patients at risk for renal failure. Rarely, if ever, are drug levels or anti-Xa-activity needed for standard therapy. When it comes to acute surgery, tPA or in case of bleeding, having drug levels at hand is, well, handy.

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