Sunday, July 22, 2012

Bridging with enoxaparin in patients with mechanical heart valves

We often have patients with mechanical heart valves who require temporary discontinuation of warfarin in preparation for surgery or an invasive procedure.  Because these patients are at such high risk for valve thrombosis, they are commonly bridged with a parenteral anticoagulant until the INR becomes sub-therapeutic. Prior to a procedure, intravenous (IV) unfractionated heparin (UFH) is usually preferred, as the agent can be discontinued several hours prior to the procedure. Immediately afterwards, patients require bridging back to warfarin until their INR is therapeutic again. I usually recommend enoxaparin, a low molecular weight heparin (LMWH) for this purpose, as it allows patients to be discharged and have their INR managed as an outpatient. I sometimes get surprised looks from the team, as many clinicians feel compelled to keep patients hospitalized on a UFH infusion until their INR is therapeutic.

I can understand their reluctance given the "Dear Health Care Professionals" letter issued in 2002 by Sanofi-Aventis, the manufacturer of Lovenox (enoxaparin).  The letter accompanied a labeling change where providers were urged not to use enoxaparin in patients with mechanical heart valves. Although the labeling revision stopped short of making it a black box warning, many clinicians considered the letter to essentially mean just that.

The labeling revision was prompted by a small study in pregnant women with mechanical heart valves in which enoxaparin was used as the sole anticoagulant (i.e., not as a bridge to warfarin). Given the  teratogenicity of warfarin, an alternative method of anticoagulation is necessary to prevent valve thrombosis in these patients during pregnancy. Unfortunately, the trial was terminated early due to an increased rate of valve thrombosis and death.  Although pregnant women are already at an increased risk for thromboembolism and have altered pharmacokinetics (e.g., volume of distribution) that may cause them to respond differently to enoxaparin than non-pregnant patients, the risk associated with enoxaparin was extrapolated as applying to all patients with mechanical heart valves.

However, in the years following the 2002 revision, the approved label has since been softened to state the following:
The use of enoxaparin has not been adequately studied for thromboprophylaxis in patients with mechanical prosthetic heart valves and has not been adequately studied for long-term use in this patient population. Isolated cases of prosthetic heart valve thrombosis have been reported in patients with mechanical prosthetic heart valves who have received enoxaparin for thromboprophylaxis.

Isolated cases of valve thrombosis have also been reported with subcutaneous UFH, intravenous UFH, and warfarin (even in the setting of a therapeutic INR). In other words, patients with mechanical heart valves are at high risk for thromboembolic events, no matter the anticoagulation strategy utilized.

So what are clinicians to do?

Evidence exists to support the use of enoxaparin as a bridge to warfarin in non-pregnant patients with mechanical heart valves [1].  In a prospective study of 250 patients being transferred to a rehabilitation center following mechanical valve replacement surgery, no increased rates of valve thrombosis or bleeding were observed with the use of an enoxaparin bridge to warfarin. Patients had been managed with an IV UFH infusion prior to transfer to the rehabilitation facility, where they continued enoxaparin until their INR was therapeutic. The transition from UFH to enoxaparin occured at approximately 16 ± 11 days after surgery, but the mean INR was subtherapeutic (1.5 ± 0.3) at this time of transition. Furthermore, the mean duration of enoxaparin therapy was 8.3 ± 6.0 days.  Given the high risk for thromboembolic events present in the population enrolled (e.g., advanced age, concomitant risk factors), one would have expected thrombotic events to occur had the therapy been ineffective.

The practice of using enoxaparin is also supported by the 2012 CHEST guidelines [2], although they give it their lowest recommendation and evidence rating (Grade 2C). That being said, the guidelines do not recommend any alternatives that have better evidence ratings -- in fact, they even recognize prophylactic doses of UFH and LMWH as being better than IV UFH, although I would never recommend these strategies in such a high-risk population

In summary, I tend to recommend the use of therapeutic enoxaparin as a bridge to warfarin in patients with mechanical heart valves after surgery or invasive procedures. The majority of these patients already have a stable warfarin regimen and should obtain a therapeutic INR within a short period of time. Besides, even if IV UFH was marginally better than LMWH, this advantage would probably be outweighed by the adverse effects of prolonged UFH infusions (e.g., heparin-induced thrombocytopenia) as well as the need to remain hospitalized for extended periods of time, where the risk of thromboembolism (not to mention infection, falls, and a myriad of other complications) are also higher. Given the current evidence to support this practice, as well as recognition by clinical practice guidelines, providers should feel comfortable discharging patients on an enoxaparin bridge to warfarin and having their INR followed in the ambulatory setting.

  1. Meurin P, Tabet JY, Ben Driss A, et al. Low-molecular-weight heparin as a bridging anticoagulant early after mechanical heart valve replacement. Circulation. 2006 Jan 31;113(4):564-9.
  2. Whitlock RP, Sun JC, Teoh KH, et al; American College of Chest Physicians. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e576S-600S.


Jill said...

I hate mechanical heart valves, fyi. Ha.

Anonymous said...

My Mother had a heart valve fitted aged 70 she died aged 83 i believed by negligence on the part of Vitamin K overdose and Clexane. This is why i believe my Mother died she had been on warfarin for 13 years and her INR was controlled by a coagulant Nurse. My Sister who lives with my mother took her to hospital for a scan because she was worried about her color she had scan and it was okay she spotted her INR nurse so my sister asked her to do a reading because her appointment was the same day has the scan. The Nurse okay and told my sister it was very low she should go to the hospital straight away in case she had a brain bleed . My sister took her to hospital and explained the Nurse had faxed the hospital what was wrong with my Mother but they said they never received any .The hospital called a local Doctor in because of staff shortages he gave my Mother double the recommended dose of Vitamin K and sent my Mother Home. tHE NEXT DAY mY Mother went back concerned because my Mother had blared vision for a short spell thinking it could be a bleed she went back and the Doctor went ma saying he would not have given my Mother such a big dose he had no choice but to put her on clexane we all suspect attacked the Mechanical heart valve with vegetation has describe after her post mortem and inquest . This is what we belive killed my Mother Vitimin K high dosage caused her blood to go from water to soup and becausethe Aiortic Mechanical valve is bigger it excepted the thickerblood and damaged the ventricle mitral valves by stretching them into stenosis state . This caused Kidney failure and heart block and sadly her death all preventable with simple stabilizing her INR and checking for water infection