Some Current Findings that Might Change Health-Care Recommendations

By Michael Jorrin, "Doc Gumshoe", August 19, 2020

If there is a single lesson to be learned from the (I hope) valuable information in this piece, it is that health-care recommendations are somewhat fluid and also somewhat temporary.   Attached to every guideline and recommendation and even to every firmly-stated conclusion in every written or spoken utterance about health care and related medical matter should be a proviso, in bold type: “This is based on what we know at this time.   As we get more information, our conclusions may change.”

That applies also to this Doc Gumshoe piece, which is mostly based on a very careful and thorough literature search published in the American Journal of Medicine  (“Update in Outpatient General Internal Medicine: Practice-Changing Evidence Published in 2019.” Wingo MT. Am J. Med 133 (2020);7:789-794).   That paper, in turn, is based on a search of the most respected medical journals on the planet, including The New England Journal of Medicine, Lancet, Annals of Internal Medicine, Journal of the American Medical Association, British Medical Journal and several others.   I list them to support my claim that at this point in time, most of this information is valid.  

Persons with atrial fibrillation and stable coronary artery disease can benefit from anticoagulation therapy without antiplatelet therapy.

Both atrial fibrillation and coronary artery disease (CAD) are very common.   Up to 6 million persons in the US have atrial fib, and nearly 20 million have CAD.   I have no data as to the overlap – how many people have both; however, atrial fibrillation by itself is not a particularly dangerous condition.   During episodes of atrial fibrillation, the circulatory system is not working as it should, and the person with atrial fib feels the effects of insufficient oxygen delivery to the tissues.   This can include weakness, dizziness, fatigue, chest pain, and others.   However, in some cases, atrial fibrillation can lead to strokes and myocardial infarctions. 

The atria are the two upper chambers of the heart, which normally receive blood and pump it into the two lower chambers (the ventricles).   These then contract and send the blood on its way – the right ventricle sends the blood into the lungs to absorb oxygen, and the left ventricle pumps newly oxygenated blood into the arterial system to be transported into all parts of the body.   What happens in atrial fib is that the atria contract at a much faster rate – two to three times the normal heart rate – but these contractions fail to expel all the blood, leaving a part of it in the atrium after each contraction.   This is the feature of atrial fib that is most serious.   Clots may form in the blood that pools in the atria, and these clots may be carried to other parts of the body, causing strokes or heart attacks.   Thus, a treatment goal in atrial fib is the prevention of clot formation.   Fortunately, because the atria are separated from the ventricles by a layer of fibrous tissue, atrial fib does not transmit to the ventricles to cause ventricular fibrillation, a much more serious and frequently fatal condition.

Guidelines in the US for patients affected by both atrial fib and coronary artery disease are somewhat confusing: they recommend four to six weeks of dual antiplatelet therapy plus an oral anticoagulant, followed by a P2Y12 inhibitor plus an oral anticoagulant.   

Before you click the little X at the upper right hand corner of your screen and banish Doc Gumshoe’s murky maunderings, let me attempt to infuse those guidelines with some clarity.   First, is there any real difference between anticoagulants and antiplatelets, since both terms refer to drugs that prevent, or at least slow down, the formation of blood clots?   The simple answer is that antiplatelet agents, including aspirin, prevent the aggregation of blood cells by inhibiting thromboxane, the enzyme that causes clot formation.   Anticoagulants accomplish much the same result by inhibiting the formation of fibrin, which also favors clot formation.   P2Y12 is the adenosine diphosphate receptor on blood platelets; P2Y12 inhibitors include those same antiplatelet agents other than aspirin.   Perhaps the use of the term “P2Y12 inhibitors” is shorthand for “antiplatelet agents other than aspirin.”

Drugs considered antiplatelet agents, besides aspirin, include Brilinta (ticagrelor), Effient (prasurgel), Plavix (clopidogrel), and Ticlid (ticlopidine).    Anticoagulants include Coumadin (warfarin), heparin, Eliquis (apixaban), Pradaxa (darigatraban), and Xarelto (rivaroxaban).   I suspect that the term “anticoagulants” came into use to distinguish the newcomers, like Eliquis, Pradaxa, and Xarelto, from the older established drugs that were in wide use.         

The AMJ paper cited above asserts that “evidence was previously lacking for optimal management of coexisting atrial fibrillation and chronic, stable coronary artery disease (beyond 12 months.)”   Now, evidence has emerged, based on an open-label multicenter trial in 2,236 Japanese patients meeting those criteria.   The subjects were assigned either to treatment with Xarelto alone or to Xarelto plus either aspirin or another antiplatelet agent. 

A higher percentage (5.75%) of the subjects on the dual therapy experienced the adverse outcomes (death, stroke, embolism, heart attacks, or unstable angina) than did the subjects taking Xarelto alone (4.14%).   This translates to a 36% edge, and it was considered to be highly significant (P < 0.001).   The trial was stopped early because of a