Goodbye to Andexanet Alfa (AndexxaⓇ)

Andexanet alfa (Andexxa) made its quiet exit from the U.S. market just a few weeks ago.  It's an interesting story so in case you missed it, I'll recap what andexanet alfa is, or rather was, and what happened that led to its removal.  Being pulled from the U.S. market may have come to a surprise for some considering its main study (ANNEXA-I) was stopped early for successfully meeting its main efficacy outcome. While having a trial stopped early for superior efficacy results sounds good on the surface, it can have negative ramifications on other aspects of the clinical inquiry (explained below).

Dyspnea Associated with Ticagrelor

Ticagrelor is an antiplatelet medication that is commonly used for a number of cardiovascular conditions.  Its mechanism is similar to that of antiplatelet medications clopidogrel and prasugrel in that it inhibits P2Y12 ADP receptors on platelets, preventing platelet activation and aggregation.  Ticagrelor is different from clopidogrel and prasugrel in that it binds reversibly to the receptor and, importantly, it is administered as the active compound.  This contrasts with clopidogrel and prasugrel which require metabolic activation by CYP450 enzymes and are therefore susceptible to drug interactions and altered activation in those with polymorphic CYP450 phenotypes (clopidogrel requires two CYP450 enzyme steps for

Beers Criteria Update 2023 - Seven Changes

The American Geriatrics Society (AGS) 2023 updated AGS Beers Criteria® for potentially inappropriate medication (PIM) use in older adults was released during the AGS annual meeting in May 2023.  This is the sixth update to the criteria which are currently designed to identify potentially inappropriate medications (PIMs) that are best avoided in older adults in general or in specific circumstances.  The criteria were first intended to be applied to the nursing home population but were expanded to apply to all adults 65 years old and older (except for end-of-life settings). 

Warfarin dosing nomogram for initiating therapy

A 60 year old female patient presents to the emergency department with complaints of swelling and pain in her right leg.  She recently had her knee replaced and has healed well since the procedure.  She has a PMH of HTN and CKD (Stage IV).  She has no other complaints at this time.  She is diagnosed with a proximal DVT on lower extremity ultrasound and the decision is made to anticoagulate her with warfarin plus a parenteral anticoagulant.  Her baseline INR is 1.28.  What strategy can we use to initiate her on warfarin to reach a therapeutic INR in a reasonable amount of time without overanticoagulating her?

Dabigatran reversal with idarucizumab (Praxbind)

A 77 year old black patient is admitted to the hospital for a gastrointestinal bleed.  He has a past medical history of CAD (MI 15 years ago), CKD (stage 4), atrial fibrillation, PUD, and hyperlipidemia for which he is taking ASA 81 mg daily, metoprolol tartrate 50 mg twice a day, atorvastatin 20 mg daily, lisinopril 20 mg daily, omeprazole 20 mg daily, and dabigatran 75 mg orally twice a day.  Initial labs indicate an aPTT of 95 seconds, hemoglobin of 6.8 g/dL, and serum creatinine 2.3 mg/dL.

Direct oral anticoagulants to treat VTE in patients with cancer?

Four direct oral anticoagulants were approved by the FDA in the last few years and are all now indicated for the treatment of DVT and PE.  These include:

• Direct thrombin inhibitor:

     -Dabigatran (Pradaxa)

• Factor Xa inhibitors:

     -Rivaroxaban (Xarelto)
     -Apixaban (Eliquis)
     -Edoxaban (Savaysa)


These medications are given orally at fixed doses and do not require coagulation monitoring or titration.  Compared to warfarin (which needs close INR following and can vary drastically

10 things you should know about target-specific oral anticoagulants

Here are some stand-out facts and tips about the target-specific oral anticoagulants.  These agents are becoming increasingly popular in the last few years and there are some nuances among them that you’ll find here. 

To review, target-specific oral anticoagulants (TSOACs) includes dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa).  They’re given orally with either once or twice daily dosing and you don’t need to (and in fact, can’t) monitor any coagulation labs in the typical clinical setting. 

Aspirin for primary prevention of cardiovascular disease and predicting risk of first cardiovascular event

The benefit of aspirin in reducing cardiovascular (CV) events or mortality in those patients with known CV disease (secondary prevention) is well established.  However, the benefit of aspirin in those without CV disease (primary prevention) is less clear.  Various organizations have differing opinions and recommendations regarding who, if anyone, should receive aspirin in this capacity, and their recommendations are summarized further below.  To go straight to the current recommendations, skip down to 'Current Recommendations'.

Heparin-induced hyperkalemia

Heparin and low molecular weight heparins (LMWH) are some of the many medications that have been identified to cause hyperkalemia.  When looking for more information about this in the prescribing information, Lexicomp, and Micromedex, there is a paucity of information.  

The prescribing information does not mention potassium at all, merely stating that suppression of aldosterone synthesis has been reported, whereas the other sources give rates from <1% to 8%.  The following will discuss the typical time course and extent of changes in potassium identified in some studies, the proposed mechanism for these effects, and risk factors.

Bridging anticoagulation when treating venous thromboemboli

Given the rising number of options for treating venous thromboemboli (VTE), questions occasionally arise on what is the standard for initiating and continuing anticoagulation.  Questions such as, "How long do we need to overlap parenteral anticoagulation for?" and "Can we begin monotherapy with a new oral anticoagulant?" will be discussed below.

4 T's - Determining the probability of HIT

An earlier post discussed how to bridge argatroban to warfarin in patients with HIT but didn't cover how to determine the likelihood of HIT when it is suspected.  This post will cover the 4 T's that are used to quantify this probability and guide clinical decision-making.

Argatroban and warfarin dosing in heparin-induced thrombocytopenia

Let’s start with a patient case.  A 45 year old woman is referred to the hospital after seeing her primary care physician for unusual bruising.  She was discharged four days ago after a two day hospitalization for an asthma exacerbation.  Her PMH includes HTN and asthma.  Her CBC reveals platelets of 73 (baseline 190) and the comprehensive metabolic panel and CBC are otherwise within normal limits.  The diagnosis of heparin-induced thrombocytopenia (HIT) is suspected since she received heparin for DVT prophylaxis during her recent hospitalization.

To see another post on how to determine the probability of HIT by using the 4 T's score, click here.

If the diagnosis of HIT is confirmed, discontinuation of all forms of heparin is paramount.  This includes unfractionated heparin and low molecular weight heparins (including flushes and heparin-coated catheters).

After diagnosis, the decision needs to be made whether to institute a non-heparin anticoagulant, a vitamin K antagonist, and/or simply discontinue all heparins.

Update to anticoagulation in atrial fibrillation

Let’s start with a patient case. A 72 year old female presents to the hospital with fatigue, palpitations, and shortness of breath that has occurred intermittently over the last two weeks.  Her PMH is significant for anxiety, seasonal allergies, and PAD which is rarely symptomatic and not lifestyle-limiting.  She is admitted to the hospital with the diagnosis new-onset atrial fibrillation.  What anticoagulation strategy is recommended for someone like this?

This pharmacy pearl highlights just a few of the key points regarding anticoagulation from the 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation which was just published in April of this year.¹  There are several differences between this newest guideline and the most recent version of the Chest guidelines from 2012 (which only addressed warfarin and dabigatran since it was the only new oral anticoagulant approved at the time).  Note that this entire summary will be referring to nonvalvular atrial fibrillation.

Drug interaction between warfarin and acetaminophen?

The management of anticoagulant therapy is an important component of the treatment of various disease states. Maintaining the narrow therapeutic range required for the safe and effective use of warfarin is essential to avoid suboptimal dosing and adverse events. Numerous drug interactions with warfarin are present due to alterations in absorption, distribution, and metabolism.  The severity of interactions with warfarin varies greatly and dictates very different recommendations for management and monitoring. In the most insignificant interactions, no change in dosage or monitoring is necessary, whereas some interactions require a significant empiric reduction in warfarin dosage and close monitoring of INR.

Does enteric coating aspirin change efficacy or adverse effects?

Bleeding risk with anticoagulant and antiplatelet medications is something that we struggle with on a regular basis.  Should we fully anticoagulate a patient with atrial fibrillation who is falling?  Should we continue the aspirin and clopidogrel even though it’s X number of months since their stents? 

Dabigatran with mechanical heart valves?

This week, the RE-ALIGN study was published in the New England Journal of Medicine, examining the use of dabigatran in patients undergoing a mechanical valve replacement or who underwent one at least three months earlier.  This study was a dose-finding study for dabigatran primarily looking at plasma trough concentrations in patients receiving 150-300 mg po bid depending on renal function (Yes, higher than doses used for atrial fibrillation).  The pharmacokinetic model used in the RE-LY study (the >18,000 patient study resulting in approval of dabigatran) was used to target certain trough concentrations and dabigatran titration was performed at prespecified intervals. 

Vitamin K administration – Routes comparison

Let’s start with a patient case.  A patient is admitted to the hospital with a CHF exacerbation.  They are taking warfarin for atrial fibrillation and their coagulation panel reveals an INR of 8.  What are our options for administering vitamin K and some of the nuances for each route of administration?

Scenarios similar to this are common occurrences in the internal medicine setting as heart failure is an independent risk factor for overanticoagulation.  The decision whether or not to use vitamin K should be based on several factors which will not be addressed now.

Vitamin K can be administered by the oral, intravenous, intramuscular, or subcutaneous routes.  Vitamin K is a fat-soluble vitamin of which there are two types; one we find in green vegetables (and lots of other foods) and the other is synthesized by intestinal bacteria.  The vitamin K that we give for therapeutic use is the former, phytonadione.¹