atrial fibrillation management

1. ATRIAL FIBRILLATION IN
CRITICALLY ILL PATIENTS
Ahmed Mohamed Abdelazeem
Critical Care Medicine Department
Benha University
2018

2. INTRODUCTION
 Atrial fibrillation (AF) is the most common cardiac arrhythmia in the intensive
care unit (ICU) setting
 Its incidence continues to rise, affecting up to 10% of patients admitted to a
general ICU and up to 50% of those admitted to a cardiac ICU

3. PREDISPOSING FACTORS
 Hypertension
 Coronary artery disease
 Heart failure
 Any acute or chronic structural heart disease
 Obesity and sleep apnea
 Pulmonary diseases: COPD, pulmonary embolism
 Atrial inflammation: pericarditis, myocarditis
 Metabolic disorders: alcohol, hyperthyroidism, hypokalemia
 Postoperative state (cardiac, pulmonary, or esophageal surgeries)

4. TYPES
 Paroxysmal AF : AF that terminates spontaneously in less than 7 days (often
24–48 hours). AF that is terminated with cardioversion at ≤7 days of onset is
also considered paroxysmal AF
 Persistent AF : AF that persists over 7 days or requires cardioversion at >7
days (or unknown duration)
 Long‐standing persistent AF : continuous AF that persists greater than 12
months, yet the adoption of a rhythm‐control strategy is still planned.

5.  Permanent or chronic AF : in cases of failure of cardioversion attempts, early
recurrences after cardioversion, or decision not to cardiovert
 Lone AF : AF that occurs in patients younger than 65 years without
underlying heart or lung disease and without hypertension
 Newly diagnosed af or “first‐detected AF” could fall into either one of these
categories
 Valvular AF : AF associated with mitral stenosis, prosthetic heart valve
(mechanical or bioprosthetic valve), or mitral valve repair

6. MORBIDITY ASSOCIATED WITH
AF
 Heart failure (loss of atrial contraction and high ventricular rate impair the
ventricular filling. The loss of the atrial kick is particularly detrimental in patients
with diastolic dysfunction, such as left ventricular hypertrophy of any cause. Left
atrial pressure increases, causing pulmonary venous hypertension and
subsequent pulmonary edema. When stroke volume deteriorates, cardiogenic
shock develops )
 Myocardial ischemia (high heart rate and secondary elevation of end-diastolic
ventricular pressure increase the myocardial oxygen demands)

7.  Subsequent tissue hypoxia (svo2 < 65%, lactate> 2.0mmol/l) and organ
dysfunction (encephalopathy, acute kidney injury and liver dysfunction)
 Uncontrolled tachycardia for the duration of days to weeks may cause
tachycardia-induced myocardial dysfunction (tachycardiomyopathy) leading to
severe systolic heart failure, which is potentially reversible after appropriate
treatment
 Thrombus formation in the left atrial appendage followed by thrombus
embolization

8. MANAGEMENT

9. MANAGEMENT OF PATIENTS WITH
HEMODYNAMIC INSTABILITY
 Urgent electrical cardioversion
 Hemodynamic instability defined as :
• Hypotension (MAP<60 or SBP <90 or 50% increase in vasopressors during first
2 hours of AF)
• Myocardial ischemia
• Pulmonary edema
Typically, to attribute hemodynamic compromise to AF, the heart rate must be >150
bpm

10. MANAGEMENT OF
HEMODYNAMICALLY STABLE
PATIENTS

11.  Acute rate control :

12.  Acute AF often spontaneously resolves by 24 hours, in ~60% of the cases,
even more so in the absence of heart disease.
 If it persists beyond 24 hours:
RHYTHM CONTROL VERSUS RATE CONTROL STRATEGY

13.  Long‐term rhythm control, as compared with rate control, has not been shown
to improve mortality, stroke rate, or HF hospitalizations in patients at high risk
of stroke or AF recurrences (AFFIRM and RACE trials), and in stable HF
patients with EF <35% (AF‐CHF trial)
 In fact, rhythm control was associated with a higher rate of hospitalization for
recurrent AF and drug‐related bradyarrhythmias and tachyarrhythmias
 In addition, in the AFFIRM trial, rhythm control was associated with increased
non‐cardiac mortality, particularly when amiodarone was used (pulmonary and
cancer mortality)

14.  The 2016 European Society of Cardiology Guidelines for the management of AF
state that “Rhythm control therapy is indicated for symptom improvement in
patients with AF” (class I indication)
 Rhythm control is still a valid strategy in patients who are symptomatic despite
rate control and who have a good likelihood of maintaining sinus rhythm
 Rate‐control drugs should be continued during a rhythm‐control strategy to
ensure adequate rate control during AF recurrences, unless the baseline sinus
rate is slow
 AV nodal ablation with ventricular pacing is the ultimate and definite therapy for
AF that cannot be rate‐ or rhythm‐controlled

15. CASES IN WHICH A RHYTHM‐CONTROL
STRATEGY SHOULD BE CONSIDERED
 Intolerable symptoms despite rate control
 Difficulty in achieving adequate rate control; or alternation of fast AF with sinus
bradycardia, precluding the optimal use of rate‐controlling drugs
 Newly diagnosed, symptomatic AF, even if symptoms get controlled with rate
reduction. This particularly applies to a young patient. 21% of patients in whom AF is
newly diagnosed are asymptomatic; these patients are unlikely to benefit from a
rhythm‐control strategy
 Decompensated HF (rhythm control after stabilization and diuresis); or advanced,
class III–IV HF (not well represented in the AF‐CHF trial)
 Other potential HF indications: diastolic HF; RV failure, where AV synchrony is critical
 Age <65 years (Most patients in the AFFIRM and RACE trials were older than 65. A
recent meta‐analysis suggests that rhythm control may improve mortality in patients
younger than 65)
 AF secondary to a treated precipitant (ischemia, hyperthyroidism)

16. RISK FACTORS ASSOCIATED WITH FAILURE OF
DIRECT‐CURRENT CARDIOVERSION, RECURRENCE OF AF
AFTER CARDIOVERSION, OR PROGRESSION OF PAROXYSMAL
AF TO PERSISTENT AF
• Severe left atrial enlargement, i.e. anteroposterior diameter >4.5–5 cm
• AF duration of more than 1 year
• Decompensated HF or decompensated medical condition that has not been
treated, e.g., hyperthyroidism
• Previous recurrences of AF, especially ≥2 recurrences requiring cardioversion
• Morbid obesity
• Underlying HF or structural heart disease
• COPD
• Age >70–75 years

17. HATCH score
 Risk score that predicts the progression from paroxysmal to persistent or
permanent AF
 HAT2CH2 (Hypertension, Age >75, TIA or stroke 2 points, COPD, HF 2
points)
0 or 1 → <10% risk of progression at 1 year
2–5 → 25–30% risk of progression at 1 year
6 or 7 → 50% risk of progression at 1 year
 Potentially harmful drugs and interventions, including cardioversion, may be
avoided in patients with a high HATCH score

18. RATE CONTROL
 Target Heart Rate
 Normal LV function, and mild or no symptoms :
Lenient rate control strategy (heart rate <110 bpm at rest)
Note that most patients in the lenient group had a heart rate <100 bpm (85 ± 14 bpm), which
implies that 100 bpm may be a better lenient goal than 110 bpm
serial echocardiograms (Q6–12 months) need to be performed to ensure a stable LV function
and the lack of progression to a tachycardia‐mediated cardiomyopathy
 Heart failure, or severe symptoms despite lenient control (intolerable palpitations,
unexplained dyspnea, or fatigue interfering with the quality of life) :
Strict rate control strategy (heart rate to <80 bpm at rest, <110 bpm with moderate activity or
6‐minute walk, and to reduce the average heart rate to <100 bpm on 24‐hour Holter monitoring)
if symptoms persist despite strict rate control, rhythm control should be considered

19.  Drugs
 β‐blockers are the most effective rate‐controlling agents chronically, are
effective as monotherapy in up to 70% of patients with AF and may be used
acutely in LV diastolic HF and in LV systolic dysfunction without clinical HF
 Digoxin is less effective as monotherapy and is poorly effective for rate control
during exertion. Digoxin is only used as monotherapy in decompensated
systolic HF or low blood pressure, when the acute initiation of β‐blockers is not
possible

20.  If the rate is inadequately controlled with the maximum tolerated dose of a
β‐blocker, digoxin or diltiazem is added as a second‐line agent; diltiazem is not an
appropriate option in systolic HF. The combination of β‐blocker and verapamil has
a strong negative inotropic effect and should be avoided in all patients. Triple
combination is required in ~15–20% of the cases, but increases the risk of
excessive pauses
 The remaining patients cannot be rate‐controlled with drugs and require rhythm
control, provided that long‐term success can be expected, or failing that,
atrioventricular nodal ablation with ventricular pacing
 Amiodarone has the theoretical risk of acutely cardioverting AF in a patient who
may have an atrial appendage thrombus, but the short‐term likelihood of
cardioversion in a patient with HF or critical illness is low. Neither ACC nor ESC
guidelines insist on this risk

22. AF AND HEART FAILURE
 If a patient presents with acute severe HF and newly detected AF with a rate
>150 bpm, AF may be considered an immediate cause of HF and acute DCCV
may be considered to improve LV diastolic filling
 If a patient presents with severe HF and AF at a rate of 100–150 bpm, acute
DCCV is generally not beneficial. AF may be:
 secondary to HF
 the cause of the cardiomyopathy and HF (tachycardia‐mediated
cardiomyopathy)
 the major trigger of HF decompensation in a patient with a previously stable
cardiomyopathy

23.  The key here is to treat HF with diuresis and vasodilators. This alone slows down
AF and possibly converts it
 Once HF is stabilized and diuresed, the goal becomes to slow down AF to a rate
<80 bpm at rest and possibly cardiovert it; at the Compensated stage, this
reduces HF symptoms and the risk of decompensation, and reverses the
possible tachycardia‐mediated cardiomyopathy

26. RHYTHM CONTROL

28. PERICARDIOVERSION
MANAGEMENT
 AF that has lasted 48 hours or more :
 TEE or 3 weeks of anticoagulation is required before DCCV
 Anticoagulation is required for at least 4 weeks after spontaneous or active
cardioversion, regardless of whether the patient’s risk factors dictate long‐term
anticoagulant therapy. AF conversion to sinus rhythm is followed by a few weeks
of atrial hypocontractility, during which a thrombus may form then embolize once
the atria fully recover their contractility. If the patient does not have an indication
for chronic anticoagulant therapy, administer warfarin or another oral anticoagulant
for 4 weeks only

29.  AF that has lasted <48 hours :
 cardioversion of AF that has lasted <48 hours does not mandate, per se, TEE or
oral anticoagulation before
 The issue is, however, that AF may have been asymptomatic for some time
before symptoms developed; symptoms may correspond to acceleration of AF
rather than its onset. In addition, one study has found that as many as 12% of
patients with AF <48 hours have LAA thrombus or dense spontaneous echo
contrast, particularly if underlying heart disease is present. Thus, a safe
approach may be to perform TEE regardless of the presumed AF duration,
especially in case of underlying heart disease

30.  If the initial TEE shows LAA thrombus, anticoagulation should be given for at
least 3 weeks, followed by a repeat TEE to document thrombus resolution
before cardioversion. If thrombus persists, consider a rate control strategy
 In 25% of patients, DCCV fails or AF recurs after a few seconds or minutes of
sinus rhythm; in another 25%, AF recurs within 2 weeks. Recurrences may
benefit from a second attempt at DCCV after preparation with an
antiarrhythmic drug. If DCCV fails or if AF recurs within 2 weeks despite an
antiarrhythmic drug, a decision may be made to accept the progression to
permanent AF

33. LONG TERM
ANTICOAGULATION

34. STROKE RISK
 CHA2DS2‐VAS improves the predictive value of CHADS2 and is particularly useful
for further classifying a CHADS2 score of 0 or 1. In fact, some patients with CHADS2
score of 0 or 1 have a high stroke risk
 The absolute stroke reduction with warfarin only overcomes the bleeding risk when
the stroke risk is ≥1.7% per year; the equipoise point is 0.9% with the newer oral
anticoagulants
 In the ESC and ACC guidelines, no antithrombotic therapy (not even aspirin) is
recommended for patients with a CHA2DS2‐VAS score of 0 (or 1 from female sex
 Anticoagulation is recommended for a score of 2

35.  For a score of 1 (excluding female sex), ESC guidelines suggest oral anticoagulation
after assessment of bleeding risk, while the ACC guidelines suggest oral
anticoagulation, aspirin, or no antithrombotic therapy. In fact, for a CHA2DS2‐VAS
score of 1, the benefit of anticoagulation is marginal, as the absolute stroke risk is
1.5–2% per year; the stroke reduction with warfarin only balances the bleeding risk.
Anticoagulation is likely beneficial if the risk factor is age 65–74 (stroke risk ~3% per
year), if the risk factor is severe (uncontrolled diabetes, low‐output severe HF), or if a
new oral anticoagulant with less intracranial bleeding risk is used
 CHADS2 score does not apply to patients with valvular AF, who have a high stroke
risk and require anticoagulation with warfarin regardless of the score
 Also, regardless of CHADS2 score, patients with hypertrophic cardiomyopathy and
AF have a high stroke risk that warrants anticoagulation

40. BLEEDING RISK

41.  A high HAS‐BLED score (A score ≥3) warrants the correction of bleeding risk
factors rather than the exclusion of anticoagulation :
 Five of the seven HAS‐BLED risk factors are modifiable
 Patients with a high HAS‐BLED score usually have a high CHA2DS2‐VAS
score and a high stroke risk, the absolute stroke risk increasing more sharply
than the bleeding risk. Thus, these patients derive an even greater net clinical
benefit from anticoagulation than patients with a low HAS‐BLED score and
should generally receive anticoagulation

42. ANTIPLATELET THERAPY AS AN
ALTERNATIVE TO ORAL
ANTICOAGULANTS The evidence supporting antiplatelet monotherapy for stroke prevention in AF is very
limited :
 VKA therapy prevents stroke, systemic embolism, myocardial infarction, and vascular
death better than single or dual antiplatelet therapy with aspirin and clopidogrel
 Antiplatelet therapy increases bleeding risk, especially dual antiplatelet therapy with
bleeding rates that are similar to those on OAC
Thus, antiplatelet therapy cannot be recommended for stroke prevention in AF patients
 the combination of aspirin and clopidogrel appears to be an option superior to aspirin
but inferior to warfarin. Since this combination has the same bleeding risk as warfarin,
it has no definite role in AF therapy, particularly with the availability of newer
anticoagulants that facilitate chronic therapy

43. ORAL ANTICOAGULANTS

44. NEW ORAL ANTICOAGULANTS
VS WARFARIN

45. WHICH ORAL ANTICOAGULANT
TO CHOOSE ?

47. PHARMACOLOGY OF NOACs

48. MONITORING OF NOACs

49. NOACS ANTIDOTES

50. NEW USES FOR NOACs ?

51. NOACs IN PATIENTS WITH
KIDNEY DISEASE

52. NOACs IN PATIENTS WITH
LIVER DISEASE

53. WHICH NOAC TO CHOOSE
?

54. BRIDGING ANTICOAGULATION IN
PATIENTS UNDERGOING
PROCEDURES
 according to ACCP guidelines, bridging with a therapeutic regimen of LMWH or IV
heparin may be performed in high‐ or intermediate‐ risk patients, while in low‐risk
patients it is reasonable to interrupt anticoagulation for up to a week without any
bridging :
 Low perioperative risk of thromboembolic events : AF with CHADS2 score of 0–2,
DVT/PE >12 months
 High risk: AF with CHADS2 score of 5–6, recent stroke/TIA (<3 months), mitral
stenosis, mechanical valve, DVT/PE <3 months
 Intermediate risk: AF with CHADS2 score of 3–4; DVT/PE within 3–12 months

55.  Warfarin is stopped 4–5 days before the procedure (4–5 doses). LMWH is started
36 hours after the last dose of warfarin, and is administered until 24 hours before
the procedure
 Warfarin is resumed on the day of surgery, while therapeutic LMWH is resumed 24
hours after a low bleeding risk procedure (endoscopy, skin biopsy) or 48–72 hours
after a high bleeding risk surgery (e.g., gastrointestinal surgery, orthopedic surgery,
pacemaker placement, polyp resection). LMWH is continued for ~5 days, until INR
is therapeutic

56.  Newer anticoagulants are more easily managed perioperatively. They have a
half‐life of 10–15 hours. They should be stopped 4 half‐lives (~2 days) before
major surgery, or 1 day before minor procedures (gastroscopy, colonoscopy
without polyp resection). They are resumed 24 hours after low‐bleeding‐risk
procedures, 48–72 hours after high‐bleeding‐risk procedures
 Renal failure particularly affects the elimination of dabigatran, which should be
held for 4 days if GFR <50, and 5 days if GFR <30. Rivaroxaban and apixaban are
less dependent on renal function and may be held for 2 days if GFR 30–50, and 3
days if GFR 15–30

58. SWITCHING BETWEEN
ANTICOAGULANT REGIMENS
 VKA to NOAC :

59.  NOAC to VKA :

60.  NOAC to parenteral anticoagulants :
The parenteral anticoagulant [unfractionated heparin (UFH) and LMWH] can be initiated
when the next dose of the NOAC would be due
 Parenteral anticoagulant to NOAC :
Intravenous UFH: NOACs can usually be started 2 (to 4) h after intravenous UFH (half-
life 2 h) is discontinued.
Low molecular weight heparin: NOACs can be initiated when the next dose of LMWH
would be due
 NOAC to NOAC :
The alternativeNOAC can be initiated when the next dose of the initial NOAC is due,
except in situations where higher than therapeutic plasma concentrations are expected
(e.g. in a patient with impaired renal function). In such situations, a longer interval in
between NOACs is recommended
 Aspirin or clopidogrel to NOAC :
The NOAC can be started immediately and aspirin or clopidogrel stopped

61. ANTITHROMBOTIC THERAPY AFTER AN ACUTE
CORONARY SYNDROME IN AF PATIENTS REQUIRING
ANTICOAGULATION

62. ANTITHROMBOTIC THERAPY AFTER ELECTIVE
PERCUTANEOUS INTERVENTION IN AF PATIENTS
REQUIRING ANTICOAGULATION

63. SECONDARY STROKE
PREVENTION

64. INITIATION OF ANTICOAGULATION AFTER TRANSIENT
ISCHAEMIC ATTACK OR ISCHAEMIC STROKE

65. LEFT ATRIAL APPENDAGE
OCCLUSION
 A novel alternative to chronic anticoagulation is percutaneous closure of the LA
appendage (e.g., Watchman device)

66. MANAGEMENT OF BLEEDING
EVENTS

67. RESUMING ANTICOAGULATION
AFTER
HEMORRHAGE Foremost on our minds tends to be the risk of another hemorrhage. Subtler to
appreciate immediately after an event is the continued risk of thrombosis, often from
the same medical condition that prompted anticoagulation therapy in the first place
 Complicating the decision, there may be a rebound effect: some thrombotic events
such as pulmonary embolism and atrial fibrillation related stroke may be more likely to
occur in the first weeks after stopping warfarin than during similar intervals in patients
who have not been taking it. The same thing may happen with the new oral
anticoagulants
 Although we have evidence-based guidelines for initiating and managing
anticoagulant therapy, ample data on adverse events, and protocols for reversing
anticoagulation if bleeding occurs, we do not have clear guidelines on restarting
anticoagulation after a hemorrhagic event

68.  This framework can help clinicians guide their patients through this challenging
clinical decision. It consists of five questions:
• Why is the patient on anticoagulation, and what is the risk of thromboembolism
without it ?
• What was the clinical impact of the hemorrhage, and what is the risk of rebleeding if
anticoagulation is resumed ?
• What additional patient factors should be taken into consideration ?
• How long should we wait before restarting anticoagulation ?
• Would a newer drug be a better choice ?

69. WHY IS THE PATIENT ON ANTICOAGULATION,
AND WHAT IS THE RISK OF
THROMBOEMBOLISM WITHOUT IT?

70. WHAT WAS THE CLINICAL IMPACT OF THE
HEMORRHAGE, AND WHAT IS THE RISK
OF REBLEEDING IF ANTICOAGULATION IS
RESUMED ?
 Different groups have defined major and minor bleeding in different ways Specifically, all
agree that a “major” bleeding event is one that is fatal, involves bleeding into a major
organ, or leads to a substantial decline in hemoglobin level. However, the Thrombolysis
in Myocardial Infarction trials use a decline of more than 5 g/dL in their definition, while
the International Society on Thrombosis and Haemostasis uses 2 g/dL

71.  Clinical impact of gastrointestinal hemorrhage :
Each year, about 4.5% of patients taking warfarin have a gastrointestinal hemorrhage, though
not all of these events are major. The newer agents (particularly dabigatran, rivaroxaban, and
edoxaban) pose a higher risk of gastrointestinal bleeding than warfarin. Frequently, endoscopy
is needed to find the source of bleeding and to control it. If this does not work, angiographic
intervention to infuse vasoconstrictors or embolic coils into the culprit artery may be required,
and some patients need surgery
 Clinical impact of soft tissue hemorrhage :
Soft tissue hemorrhage accounts for more than 20% of warfarin related bleeding events; as yet,
we know of no data on the rate with the new drugs. Soft tissue hemorrhage is often localized to
the large muscles of the retroperitoneum and legs. Much of the clinical impact of retroperitoneal
hemorrhage is from a mass effect that causes abdominal compartment syndrome, hydroureter,
ileus, abscess formation, and acute and chronic pain. It can also lead to deep vein thrombosis
from venous compression, coupled with hypercoagulability in response to bleeding. Brisk
bleeding can lead to shock and death, and the mortality rate in retroperitoneal hemorrhage is
estimated at 20% or higher. In many cases, the retroperitoneal hemorrhage will self-tamponade
and the blood will be reabsorbed once the bleeding has stopped, but uncontrolled bleeding may
require surgical or angiographic intervention

72.  Clinical impact of urinary tract hemorrhage :
Gross or microscopic hematuria can be found in an estimated 2% to 24% of patients taking
warfarin; data are lacking for the target specific oral anticoagulants. Interventions required to
manage urinary tract bleeding include bladder irrigation and, less often, transfusion. While
life-threatening hemorrhage is uncommon, complications such as transient urinary
obstruction from clots may occur
 Clinical impact of intracranial hemorrhage :
Intracranial hemorrhage is the most feared and deadly of the bleeding complications of
anticoagulation. The incidence in patients on warfarin is estimated at 2% to 3% per year.
Emerging data indicate that the newer drugs are also associated with a risk of intracranial
hemorrhage, though the risk is about half that with vitamin K antagonists. Intracranial
hemorrhage leads to death or disability in 76% of cases, compared with 3% of cases of
bleeding from the gastrointestinal or urinary tract

73.  Risk of rebleeding :
Although there are several indices for predicting the risk of major bleeding when starting
anticoagulation, there are currently no validated tools to estimate a patient’s risk of
rebleeding. The patient factor that most consistently predicts major bleeding is a history of
bleeding, particularly from the gastrointestinal tract. Finding and controlling the source of
bleeding is important
With or without anticoagulation, after a first intracranial hemorrhage the risk of another one
is estimated at 2% to 4% per year. An observational study found a recurrence rate of 7.5%
when vitamin K antagonist therapy was started after an intracranial hemorrhage
Patients with lobar hemorrhage and those with suspected cerebral amyloid angiopathy may
be at particularly high risk if anticoagulation is resumed. Conversely, initial events attributed
to uncontrolled hypertension that subsequently can be well controlled may portend a lower
risk of rebleeding
For other types of intracranial hemorrhage, recurrence rates can be even higher. In chronic
subdural hematoma, the recurrence rate after initial drainage has been estimated at 9.2%
to 26.5%, with use of anticoagulants

74. WHAT ADDITIONAL PATIENT FACTORS
SHOULD BE TAKEN INTO CONSIDERATION
? Target INR on warfarin :
When considering resuming anticoagulation after bleeding, make sure the therapeutic
target is appropriate

75.  Labile INR :
TTR on VKA therapy is an important predictor of major haemorrhage. Therefore, we
recommend targeting the INR between 2.0 and 3.0 in patients on VKAs, maintaining a
high TTR (e.g. ≥70%), and to consider switching to a NOAC when a high TTR cannot be
sustained
 Comorbid conditions :
Comorbid conditions associated with bleeding include cancer, end-stage renal disease,
liver disease, arterial hypertension, prior stroke, and alcohol abuse. Alcohol excess is a
risk factor for bleeding in anticoagulated patients, mediated by poor adherence, liver
disease, variceal bleeding, and risk of major trauma

76.  Concurrent medications :
Concomitant therapies, including antiplatelet drugs and nonsteroidal antiinflammatory
drugs, increase bleeding risk. Additionally, warfarin has many interactions. Although the
newer drugs are lauded for having fewer interactions, they are not completely free of
them, and the potential for interactions must always be reviewed
 Advanced age :
The influence that the patient’s age should have on the decision to restart anticoagulation
is unclear. Although the risk of intracranial hemorrhage increases with age, particularly
after age 80, limited data exist in this population, particularly with regard to rebleeding.
Further, age is a major risk factor for most thrombotic events, including venous
thromboembolism and stroke from atrial fibrillation, so although the risks of anticoagulation
may be higher, the benefits may also be higher than in younger patients. We discourage
using age alone as a reason to withhold anticoagulation after a hemorrhage

77. HOW LONG SHOULD WE WAIT
BEFORE RESTARTING
ANTICOAGULATION ?
 We lack conclusive data on how long to wait to restart anticoagulation after an
anticoagulation associated hemorrhage. The decision is complicated by evidence
suggesting a rebound effect, with an increased risk of pulmonary embolism and atrial
fibrillation related stroke during the first 90 days of interruption of therapy with warfarin
as well as with target specific oral anticoagulants. In anticoagulation associated
retroperitoneal bleeding, there is increased risk of deep vein thrombosis from
compression, even if venous thromboembolism was not the initial indication for
anticoagulation. In patients with intracranial hemorrhage, evidence suggests that the
intracranial hemorrhage itself increases the risk of arterial and venous thromboembolic
events

78.  Timing after gastrointestinal bleeding :
Most patients should resume anticoagulation after 4 to 7 days of interruption after
gastrointestinal bleeding
 Timing after soft tissue hemorrhage :
It is reasonable to resume anticoagulation 4 days after the event

79.  Timing after intracranial hemorrhage :
 After documentation of cessation of bleeding, prophylactic dose anticoagulation may
be considered after the first 24 to 72 hours
 The American College of Chest Physicians recommends starting prophylactic dose
heparin the day after an ICH, with no clear guidance on restarting warfarin
 The American Heart Association suggests that, in patients with a very high risk of
thromboembolism, warfarin may be restarted after 7 to 10 days
 The European Stroke Initiative recommends that, in patients with a very high risk of
thromboembolism, warfarin should be restarted after 10 to 14 days
 The European Society of Cardiology recommends that anticoagulation can be
reinitiated after 4–8 weeks, especially when the cause of bleeding or the relevant risk
factor (e.g. uncontrolled hypertension) has been treated

81. WOULD A NEWER DRUG BE A
BETTER CHOICE ?
 The new drugs, compared with warfarin, show a favorable risk-benefit profile with
reductions in stroke, intracranial hemorrhage, and mortality with similar overall major
bleeding rates, except for a possible increase in gastrointestinal bleeding
 Compared with warfarin, the risk of gastrointestinal bleeds was increased for
dabigatran 150 mg twice daily, rivaroxaban 20 mg once daily, and edoxaban 60 mg
once daily. The risk of gastrointestinal bleeding was comparable to warfarin on
dabigatran 110 mg twice daily and on apixaban 5 mg twice daily. Apixaban
demonstrated rates of gastrointestinal bleeding comparable to that with aspirin for
stroke prevention in atrial fbrillation

82.  Given the data above, when anticoagulation is to be resumed after an intracranial
hemorrhage, the risk of rebleeding, particularly in the form of recurrent intracranial
hemorrhage, may be lower if a target-specific oral anticoagulant is used
 Similarly, when anticoagulation is to be resumed after a gastrointestinal bleeding
event, reinitiation with warfarin or apixaban therapy may present the lowest risk of
recurrent gastrointestinal rebleeding
 In other sources of bleeding, such as retroperitoneal bleeding, we suggest
consideration of transitioning to warfarin, given the availability of reversal agents in
the event of recurrent bleeding

83. Other important drug specific factors :
 In patients with significant renal impairment, the choice of agent will be limited to a
vitamin K antagonist
 A meta-analysis of randomized clinical trials suggests that in the elderly (age 75 and
older) target-specific oral anticoagulants did not cause excess bleeding and were
associated with at least equal efficacy compared with vitamin K antagonists
 Target-specific oral anticoagulants may be beneficial in patients who have challenges
in achieving INR targets. On the other hand, if there is concern that a patient may
occasionally miss doses of an anticoagulant, given the rapid onset and offset of action
of target-specific agents compared with warfarin, a missed dose of a target-specific
agent may result in faster dissolution of anticoagulant effect and increased risk of
thrombotic events, and lapses in anticoagulation will not be identified by routine drug
monitoring

84. NEW-ONSET ATRIAL FIBRILLATION
IN CRITICALLY ILL PATIENTS
 New-onset AF in critical illness refers to patients with no prior history of AF who
are admitted in sinus rhythm and subsequently develop new-onset AF while
being treated for critical illness, generally in the ICU
 The main differential diagnostic consideration is previously undiagnosed
asymptomatic paroxysmal AF. Features that would support a diagnosis of new-
onset AF rather than chronic, paroxysmal AF may include symptomatic AF or
severe physiologic stress triggering transition into AF (e.g. AF immediately
following an epinephrine bolus)

85.  Most of what we know (or think we know) about AF does not apply to new-onset AF
in critically ill adults :
 Unlike in the community, new onset AF in the ICU is a transient phenomenon
 The etiology of new onset AF in the ICU is different than in the community and
modifiable risk factors are very common

86.  Despite the high incidence of new-onset AF in the general ICU population, currently
available information for AF, especially for management, is quite limited
 Unfortunately, our understanding of AF treatment is based almost exclusively on
studies of outpatients with chronic AF
 AF occurring in relation to acute triggers (sepsis, postoperative state, acute lung
disease) will likely convert once these issues are treated
 Acutely, it is treated like any newly diagnosed AF, with rate control, knowing that a
rate of 100–125 bpm may be appropriate in these critical situations. β‐blockers are
primarily used; amiodarone and digoxin may also be used for rate control in case of
borderline blood pressure or acute HF
 DC cardioversion, amiodarone for the purpose of rhythm control, or any
antiarrhythmic drug has a limited role, as AF will likely recur early on (~45%) then
convert spontaneously regardless of these measures

87. DO THE DRUGS WORK ?

88. STRATEGY FOR CARDIOVERSION
AND MAINTENCE OF SINUS
RHYTHM

90. ANTICOAGULATION
 Even short‐term AF is associated with an increased stroke risk; thus, AF lasting more
than 24 hours warrants short‐term anticoagulation according to the ACCP guidelines (4
weeks of anticoagulation)
 As in CABG, longer‐term anticoagulation and antiarrhythmic drug therapy are not
warranted If AF does not persist beyond 6–8 weeks, and in the absence of :
 AF recurrence
 Severe underlying myocardial/atrial disease or dilatation
 Persistence of the trigger (e.g. chronic severe lung disease)
 On the other hand, AF that occurs during STEMI or ACS is not simply a transient form
of AF as the underlying condition (CAD) is chronic and ischemia may be recurrent. In
this context, AF is probably best managed with long‐term anticoagulation

91. EXCESSIVE SUPRAVENTRICULAR
ECTOPIC ACTIVITY(ESVEA)
 Excessive supraventricular ectopic activity (ESVEA) was defined as ≥30 supraventricular
ectopic complexes (SVEC) per hour or any episode of runs of ≥20 SVEC
 It is found to be associated with an increased risk of ischemic stroke. The most likely
mechanism is that increased SVEC triggers atrial fibrillation or is a forerunner of atrial
fibrillation. However, there is suggestion that ESVEA increase risk of ischemic stroke
beyond atrial fibrillation. Another possibility could be that increased ESVEA is a marker of
more severe hypertension, diabetes, physical inactivity, or lipid metabolism abnormality,
thus signifying an increased vascular risk profile and an increased probability of stroke in
these subjects

94.  ESVEA is a clinically stable and consistent finding that seems to confer a stroke risk
comparable to that of AF
 The manner in which to treat patients with ESVEA to reduce the associated risk of
atrial fibrillation or stroke is currently not apparent. Subjects with ESVEA may need
strict risk factor modification and close follow-up for the early detection of atrial
fibrillation
 More investigation in this field is needed