Anticoagulation and "Valvular" Atrial Fibrillation

Heart valve failure is a mechanical problem. Of course, that is like saying that can't run is a leg problem. It's painting with a broad brush. Some valves get stiff and can't move. Some get floppy and don't close well. Some, touched by illness, don't heal well so that the corners stick together, pursed in a perpetual whistle. The last bit of attractive imagery is what happens in Rheumatic Fever, fortunately a rarity in developed countries today.

Regardless, the treatment for a valve that won't work in a heart that can't handle it is to remodel part of the valve or replace it. Nothing man-made can recreate Nature's design for the interaction between blood and the structures containing it. Sutures, sewing rings and struts of human design offer locations for clots to form and sometimes find freedom.

Therefore, when a man-made valve is placed, the self-solidifying capacity of blood is bridled by an anticoagulant. Replacements made of biological tissue are eventually accepted by the body and felt to require little in the way of "help" to retard clots as long as the heart rhythm remains normal. However, their mechanical counterparts require assistance throughout their lifetime. Without anticoagulation, their associated stroke risk is 4%/year.(1) The windsock mitral valve created by Rheumatic Fever leaves the left atrium like a balloon about to pop. As a result, the conciseness of sinus rhythm frequently degenerates into atrial fibrillation. Pooling blood in a quivering chamber with restricted outlet is a recipe for clot formation and stroke.

People with the combination of mitral stenosis and atrial fibrillation see a stroke risk of almost three out of ten every year. Therefore, when valve and stroke are considered together, it is the mitral valve that is feared most whether deformed by disease or mechanical design. Warfarin or dicoumarol is the drug of record used for protection from stroke in atrial fibrillation and from artificial heart valves. It reduces the stroke risk with a mechanical heart valve to 1%/year.(1) Neither design nor inherent virtue led to warfarin's ascendancy for long-term anticoagulation. Rather, it was the only practical anticoagulant available when the need arose. Long experience has refined its use though it remains problematic and virtually every valve recipient who uses it longs for something better. Something better is promised in a group of designed anticoagulation drugs whose behavior is far more predictable than warfarin. To the relief of all to whom they have proven valuable, they do not require periodic blood testing to guide their use. These drugs, given abbreviated references surely created by the US Army (DOAC, NVKA, etc.), have proven useful for people with blood clots in veins or who fear blood clots in veins and in the setting of atrial fibrillation. All valve owners wonder of their potential use for them.

Warfarin survived baptism by fire, a path that no drug can take to regular use today. Its alternatives require trials to prove their utility. Meanwhile, the specter of the mitral valve looms over all valve disease when combined with atrial fibrillation. Therefore, proof of value in the setting of atrial fibrillation labeled "non-valvular" leaves a question in many minds. Why not valvular and just what is non-valvular? (2)The logical first step of the makers of warfarin's better looking cousins was to dip their toes in atrial fibrillation first. Early on, an attempt with one of the new drugs to protect after valve replacement went poorly. It convinced no one that the alternatives won't work. Therefore, there is an inkling of hope in the observations made in a small number of people who helped with The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation Thrombolysis in Myocardial Infarction 48).(2) This trial was designed to examine one of the warfarin alternatives, edoxaban in comparison to warfarin in people with atrial fibrillation and an increased risk of stroke. Out of the 21,105 people who participated, 191 had a prosthetic valve (about 2/3 mitral and 1/3 aortic). People with mechanical valves, quite reasonably, could not get into the trial.

Therefore, all of the prosthetic valves were biological. Of that number, eight people out of seventy, taking warfarin had a stroke as opposed to seven out of one hundred twenty-one on edoxaban.

This observation will relax the minds of many concerned by the broadly drawn proscription on considering atrial fibrillation with any valve disease in the same light as other people with atrial fibrillation. In addition to other types of valve problems (mostly minor and not a narrowing deformity) that have benefited from the new drugs, this may push a change of reference from the oft-mentioned "non-valvular" atrial fibrillation. The burning question is now the use of these designed anticoagulants for people with mechanical valves that have been in place for some time, particularly in the mitral position.

1. Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994;89(2):635-41.

2. Carnicelli AP, De Caterina R, Halperin JL, Renda G, Ruff CT, Trevisan M, et al. Edoxaban for the Prevention of Thromboembolism in Patients With Atrial Fibrillation and Bioprosthetic Valves. Circulation. 2017;135(13):1273.

Keywords: Stroke, Atrial Fibrillation, Anticoagulant, Heart Valve