Principle

When a patient using anticoagulant needs an invasive procedure, how will you deal with the anticoagulant? It could be an important question especially for DOAC users. The picture that I have drawn is about the principle for resolving this problem.

 

Important points about DOAC that effect on bleeding risk

• The short half-life (approx. 9-15 h), but it becomes longer in renal insufficiency!
• Blood pressure, anemia, elderly, anti-inflammatory drug!
• They are not suitable in severe renal insufficiency and in liver diseases.
• Anticoagulants can accumulate in the kidneys, liver and heart failure.
• Laboratory tests should always be checked when an invasive procedure has planned; Always Creatinine, Hb or Blood Count. In need ALAT, Thromboplastin Time & activated Partial Thromboplastin Time (depending on patient's bleeding risk & procedure bleeding risk)
• Drugs affecting haemostasis; Antiplatelets (asa, clopidogrel, prasugrel, ticagrelor, dipyridamole), Selective serotonin reuptake inhibitors (SSRIs), in some cases omega 3 fatty acid & glucosamine.

 

Apixaban and invasive procedures

• Smaller dose; 2.5 mg BID in patients with any 2 of the following characteristics: Age ≥80 years, Weight ≤60 kg, Serum creatinine ≥1.5 mg/dL → So if the patient uses normal dose of Apixaban 5 mg BID, but the age is near to 80 y. and weight is slightly over 60 kg could be at high risk of bleeding in invasive procedures specially if this patient has also renal failure. → So individual assessment to evaluate bleeding risk is important.
• In case of overdose or emergency surgery, calibrated & quantitative determination of anti-FXa could be useful.
• Treatment should be discontinued at least 48 hours before an elective invasive procedure with associated risk of bleeding is moderate to high. Treatment should be discontinued at least 24 hours before an elective invasive procedure with associated risk of bleeding is low.
• Treatment should be initiated after invasive operation again as soon as possible.

 

Rivaroxaban and invasive procedures

• Stop rivaroxaban at least 24 hours before procedure
• Restart rivaroxaban after surgery/procedure as soon as adequate hemostasis is established
• If unable to take oral medication following surgical intervention, consider administering a parenteral drug

 

Dabigatran and invasive procedures

• A lower dose (110mg BID) is indicated for 80 years old (or older) or patients treated concomitantly with verapamil.
• At normal dose of Dabigatran (150 mg BID), if the patient is 75-80 years old, with moderate renal insufficiency or gastritis → The patient could be at high risk of bleeding in invasive procedures, so individual assessment to evaluate bleeding risk is important.
• If the patient is 75-80 years old, with moderate renal insufficiency or gastritis → Gastrointestinal bleeding is statistically significant, especially if this patient treated concomitantly with antiplatelet (PCI patients) → A Proton pump inhibitor is recommended.
• ECT, dTT, and aPTT can provide useful information, but the tests are not standardized.

HemOnc Today, November 25, 2011 Beth Walden, MA; Stephan Moll, MD

 

Idarucizumab for Dabigatran Reversal  (RE-VERSE AD ClinicalTrials) Charles V. Pollack, Jr., M.D.,..., Jeffrey I. Weitz, M.D. June 22 ,2015, at NEJM.org.

• Safety of 5 g of idarucizumab to reverse the anticoagulant effects of dabigatran in patients who
(group A) had serious bleeding
(group B) required an urgent procedure

• 90 patients who received idarucizumab.
• 68 patients with an elevated dilute thrombin time and 81 with an elevated ecarin clotting time at baseline → Idarucizumab normalized the test results in 88 to 98% of the patients, an effect that was evident within minutes.

• Mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient, respectively.
• Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes.
• So the approved indications for idarucizumab; 1-serious bleeding 2-urgent procedure

 

Guidance on converting between anticoagulants

From DOAC to Warfarin; DOAC should be continued for 2 days, after which point INR should be measured prior to each dose of DOAC . DOAC should be discontinued when INR is ≥ 2.0. Because Pradaxa may increase the INR, the INR test reflects the effect of Warfarin best only after the cessation of Pradaxa has passed at least two days.

From Warfarin to DOAC;
- If INR < 2 → start DOAC
- IF INR < 2.5 → start DOAC in the next day
- If INR > 2.5 → stop the warfarin and wait until INR become <2.5

From DOAC to LMWH; Discontinue DOAC and commence LMWH at the time that the next scheduled dose of DOAC would be due.
From LMWH to DOAC; Discontinue LMWH and commence DOAC 0-1 hours before the time that the next scheduled dose of LMWH would be due.

• According to the phase III RE-LY trial; The risk of bleeding in general will increase most often in situations where anticoagulant is exchanged for another. So converting between anticoagulants during an invasive procedure is not recommended.
• So AC changing, like DOAC to Warfarin during a procedure is not a good idea!

 

Evidence for Uninterrupted OAC versus Bridging Therapy during PCI for patients with AF

• In a post-hoc adjusted analysis of patients on long-term OAC undergoing PCI from the WOEST trial (n=573), Uninterrupted OAC was not associated with increased MACCE or bleeding events, compared with bridging therapy, at 30-day and at 1- year follow-up. (Dewilde W, et al. EuroIntervention 2015;11:381-90.)
• In our center (Satakunta central hospital, Pori, Finland), the policy is uninterrupted OAC (included DOAC) during PCI.

 

Combination therapy during PCI for patients with AF (ESC AF Guidelines 2016)

• The optimal combination antithrombotic therapy or duration of combination therapy for AF patients undergoing percutaneous coronary intervention is not known → Expert consensus.
• In general, a short period of triple therapy is recommended, followed by a period of dual therapy.
• When a DOAC is used, the consensus recommendation is that the lowest dose effective for stroke prevention in AF should be considered.
• When a DOAC is used, the use of prasugrel or ticagrelor as part of triple therapy should be avoided.

 

WOEST trial

• 573 anticoagulated patients undergoing percutaneous coronary intervention (70% with AF) were randomized to either dual therapy with OAC and clopidogrel or to triple therapy.
• Bleeding was lower in the dual vs. triple therapy arm.
• The rates of myocardial infarction, stroke, target vessel revascularization, and stent thrombosis did not differ.
• All-cause mortality was lower in the dual therapy group at 1 year (2.5% vs. triple therapy 6.4%).

 

Prevention of Bleeding in Patients with AF Undergoing PCI (C. Michael Gibson, M.D.,...,Keith A. Fox, M.B., Ch.B, N Engl J Med December 22, 2016)

• Randomly assigned 2124 participants with nonvalvular atrial fibrillation who had undergone PCI with stenting
- Group 1; Low-dose rivaroxaban + P2Y12 inhibitor for 12 months
- Group 2; Very-low-dose rivaroxaban + DAPT for 1, 6, or 12 months
- Group 3; Standard therapy (Triple therapy with Warfarin)

• The rates of clinically significant bleeding were lower in the two groups receiving rivaroxaban than in the group receiving standard therapy (16.8% in group 1, 18.0% in group 2, and 26.7% in group 3).
• The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups.

 

AF patient in need of OAC after PCI (ESC AF Guidelines 2016)

• We establish the strategy based on; Stroke risk, Bleeding risk & Clinical setting (elective PCI or ACS patient)
• In our center (Satakunta central hospital, Pori, Finland), we recommend Triple therapy for 1-3 months & Dual therapy for 6-12 months. We do not use Triple therapy over 3 months, based on new researches and guidelines that recommend a short period on Triple therapy.

 

Tripple therapy with Prasugrel & Ticagrelor

• OAC & PCI with DES, tripple therapy that included Prasugrel → more major and minor bleeding at 6 month follow-up, versus tripple therapy that included clopidogrel. (Sarafoff N, et al. JACC 2013;16:2060-2066)
• OAC & PCI (n=152), tripple therapy that included Ticagrelor → similar composite rate of ischemic and bleeding events at 12 month follow-up, versus tripple therapy that included clopidogrel. (Fu A, et al. Clin Cardiol 2016;39:19-23)

ESC Guideline

 

Pacemaker or Defibrillator Surgery without Interruption of Anticoagulation (David H. Birnie, M.D.,...,Vidal Essebag, M.D., Ph.D., BRUISE CONTROL, N Engl J Med 2013)

CONCLUSIONS;
As compared with bridging therapy with heparin, a strategy of continued warfarin treatment at the time of pacemaker or ICD surgery markedly reduced the incidence of clinically significant device-pocket hematoma.

 

Bridging periods off oral anticoagulation (ESC AF guidelines 2016)

Most cardiovascular interventions (e.g. percutaneous coronary intervention or pacemaker implantation) can be performed safely on continued OAC. When interruption of OAC is required, bridging does not seem to be beneficial, except in patients with mechanical heart valves.

 

Our Center's Policy during cardiologic procedures (Satakunta central hospital, Pori, Finland)

• ASA → Uninterrupted
• Dual therapy → In general should be avoided → Uninterrupted
• Warfarin → Uninterrupted
• DOAC during PCI → Uninterrupted
• DOAC during Pacemaker Surgery → In general Uninterrupted → (If bleeding risk is significant but patient's occlusion risk is low, we could interrupt NOAC one day before pacemaker surgery and also at the day of surgery in need.)

 

 

Compilation by Dr. Samad Ali Moradi, According to Guidelines & author work experience.