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Patient management


Conversion from VKA to NOAC and vice versa Patients treated with VKAs and requiring conversion to a NOAC need special attention because of the different half-lives of VKAs and NOACs. It may take up to seven days and longer to normalise coagulation after discontinuation of VKA and, therefore, INR measurements at close intervals are required after discontinuation of VKAs to detect when the INR is approaching the lower end of the recommended target range of 2.0–3.0.6


If the INR is


2.0–2.5, the NOAC can be started immediately or, better, the next day. The NOAC can be initiated immediately once the INR is lower than 2.0.5 If a patient needs to be converted from NOAC to VKA the slow onset of action of VKA needs to be considered. It may take 5–10 days or longer before an INR in therapeutic range is obtained, with large individual variations. Therefore, the NOAC and the VKA should be administered concomitantly until the INR is in a range that is considered appropriate.5


The conversion procedures from VKA to a NOAC and vice versa are represented graphically in Figures 2 and 3.


How can patients be managed who require planned or emergency surgery? In patients who require planned surgery, the key question is when to discontinue NOAC before surgery. Surgical interventions or invasive procedures that carry a bleeding risk require the temporary discontinuation of the NOAC. Both patient characteristics (kidney function, age, history of bleeding complications, concomitant medication) and surgical factors should be taken into account on when to discontinue and restart the drug. When the intervention carries no clinically important bleeding risk and/or when adequate local haemostasis is possible, such as interventions for cataract or glaucoma, or some dental procedures, the procedure can be performed at trough concentration of the NOAC (that is, 12 or 24 hours after the last intake, depending on once- or twice-daily dosing) but should not be performed at peak concentration.


For procedures with a low bleeding risk (for example, endoscopy with biopsy, prostate or bladder biopsy) it is recommended to discontinue NOACs 24


Target enzyme


Table 2: Key pharmacological characteristics Apixaban Edoxaban Rivaroxaban Factor Xa Factor Xa Factor Xa


Dosing regimen for long-term anticoagulation in AF or VTE treatment


BD


% renally excreted of absorbed dose 27% Time to peak activity Half-life


QD 50%


10–14 hours


QD 33%


3 hours 1–2 hours 2.5–5 hours 12 hours


5–9 hours


(young healthy patients); 11–13 hours (elderly patients)


Dabigatran


Factor IIa (thrombin)


BD 80% 2 hours 12–17 hours


Figure 1: Switching from NOAC to LMWH SC and vice versa


hours before the elective procedure in patients with a normal kidney function. For procedures that carry a high bleeding risk (for example, complex left-sided ablation, spinal or epidural anaesthesia, lumbar diagnostic puncture, thoracic surgery, abdominal surgery, major orthopedic surgery, liver biopsy, transurethral prostate resection, kidney biopsy), it is recommended to take the last NOAC 48 hours before. Furthermore, the renal function of the patient needs to be considered because NOACs are partially renally excreted and therefore, the recommended


pre-operative pause for dabigatran may be up four days for patients with creatinine clearance (CrCl) of 30–50ml/ min.


If an emergency intervention is


required, the NOAC should be discontinued and surgery or intervention should be deferred, if possible, until at least 12 hours, and ideally 24 hours, after the last dose. When the procedure cannot be delayed, the increased risk of bleeding should be assessed against the urgency of the procedure. In patients who require emergency surgery and where there


Figure 2: Conversion of VKA to NOAC www.hospitalpharmacyeurope.com


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