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Anticoagulants, Warfarin, Plavix, Aspirin

  Anticoagulants (blood thinners) LONG TERM:  http://healthfully.org/rc/id10.html (12/18/14)

If the number of platelets is too low, excessive bleeding can occur; however, if the number of platelets is too high, blood clots can form (thrombosis), which may obstruct blood vessels and result in such events as a strokemyocardial infarction (MI), pulmonary embolism or the blockage of blood vessels to other parts of the body, such as kidneys the extremities of the arms or legs.  To prevent these health issues pharma markets 8 families of anticoagulants:  vitamin K inhibitors, platelet inhibitors, anti-thrombin protein therapeutics, direct thrombin inhibitors, Xa inhibitors, and synthetic pentasaccharide inhibitors, fibrin inhibitors, and animal type clot inhibitors from insects, lamprey, etc.  Anticoagulants constitute the 3rd most profitable prophylactic drug intervention after statins and hypertension drugs.  Is the current level of intervention justified; and when justified, what ought to be taken? 

Rather than again visit the topic of credibility of the pill pushers, please read Marketing Science & Side Effects.  As Prof, Dr.  Marcia Angell states:  “We certainly are in a health care crisis,...  If we had set out to design the worst system that we could imagine, we couldn't have imagined one as bad as we have.” Her President’s Lecture & book on how pharma deceives us makes this point through examples.  For an explanation of how pharma manipulates the practice of medicine click on junk treatments.  Bias journal articles are the norm[1] and informed consent has become misinformed.

Aspirin, the choice of our grandparents, has fallen victim to the production of miss-information by pharma[2].  Aspirin as an anticoagulant has been replaced by 8 types of patented drugs.  However the convincing evidence for this is lacking.  In a review of the 2 leading anticoagulants, The American Heart Association (AHA) concluded that, “The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin [Coumadin] and Plavix [clopidogrel] is superior to aspirin.”   Aspirin in the medicinal dose of 325-975 mg is superior to Warfarin, Plavix, and others because it is an effective anticoagulant, best for heart attack prevention (lowers deaths 51%), and causes less serious hemorrhaging.  Thus the studies using low dose aspirin (75 mgs) are flawed.  Aspirin also reduces the risk of the most common types of cancers by over 30%, & promotes the survival of most stages I, II, & III of those cancers through the apoptosis (the death of abnormal cells), e.g., colon cancer survival up 74%, & breast cancer up 66%.  Wikipedia wrote:  “NSAIDs aside from aspirin, both newer selective COX-2 inhibitors [Celebrex, Vioxx] and traditional anti-inflammatories, increase the risk of myocardial infarction and stroke.[9][10]…. NSAIDs aside from aspirin are associated with a doubled risk of symptomatic heart failure in patients without a history of cardiac disease.”  The AHA has a similar warning.  Consider a day on NSAIDs as equal to smoking a pack of cigarettes.[3]  Aspirin also lowers the risk of Alzheimer’s diseases 60%.  Aspirin should be the drug of choice.  Anticoagulants ought not to be used after major surgery:  “The fatal pulmonary embolism rate was 0.1% to 0.2% even in patients who received no prophylaxis. This is an order of magnitude lower than that which is generally quoted, and therefore the potential benefit of prophylaxis is very small and does not justify the risks… as shown by autopsy.”  The atrial fibrillation use of anticoagulants is based on marketing science.  

Coumadin (Warfarin, a vitamin K antagonists):  This oral anticoagulant is derived from coumarin, which is found in many plants, and was originally used as a rodenticide since 1948. In the 1950s it was found to be effective and relatively safe for preventing embolism in many disorders.  “It was approved in 1954 and is the most widely prescribed anticoagulant drug in North America.  It takes at least 48 to 72 hours for the anticoagulant effect to develop. Where an immediate effect is required heparin is given. Warfarin is used for patients with deep-vein thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation(AF), and mechanical prosthetic heart valves.  Warfarin’s half life is 40 hours.  Warfarin and related 4-hydroxycoumarin-containing molecules decrease blood coagulation by inhibiting vitamin K epoxide reductase, an enzyme that recycles   oxidized  vitamin K1 to its reduced form after it has participated in the carboxylation of several blood coagulation proteins,  mainly prothrombin and factor VII.  Despite being labeled a vitamin K antagonist, [2] warfarin does not antagonize the action of vitamin K1, but rather antagonizes vitamin K1recycling, depleting active vitamin K1[3]Wikipedia.  Typical results are in a 2013 study comparing Edoxaban to warfarin in 21,105 patients for high risk with fibrillation) for 2.8 years with endpoints of stroke or systemic embolism found for warfarin 1.5% per year had those endpoints.  But major bleeding (2 or more pints of blood transfusion) was 3.43% per year.  And excluded to avoid negative results was the incidents of MI, for which warfarin has little effect upon.  Low dose Edoxaban fared about the same.  Side effects include the very serious calcification of tissues, a key element in hypertension and CVD (in the arteries calcification and buildup of plaque are their causes).  Warfarin causes cholesterol embolism (athero-embolism) resulting from the release of cholesterol from plaque.  It travels along with the blood steam (embolism) to other places in the body, where it obstructs blood vessels…. causes skin symptoms (usually livedo reticularis), gangrene of the extremities and sometimes renal failure; problems with other organs may arise, depending on the site at which the cholesterol crystals enter the bloodstream” Wiki . “Several epidemiological studies have also implicated warfarin use in valvular and vascular calcification. … a 60% increased risk of osteoporosis-related fracture in men”  Wiki.

Despite its effectiveness there are major shortcomings.   It has been used occasionally after heart attacks (myocardial infarctions), but is far less effective at preventing new thromboses in coronary arteries.  Prevention of clotting in arteries is usually undertaken with antiplatelet drugs such as aspirin, which act by a different mechanism from Warfarin (which normally has no effect on platelet function).   Warfarin accounts for one third of hospitalizations, an estimated annual 33,000 for adverse drug reactions of hemorrhaging.   Several times more major events go unreported because of lack of a legal reporting requirement, failure to associate the event as drug induced, not knowing which drug is the cause, and death. “Several studies have demonstrated a link between warfarin use and osteoporosis-related fracture.” .Warfarin interacts with a list of over 100 drugs, herbs and foods--see Worst Pill for a list.  “Most of interactions will greatly increase the effect of Warfarin by reducing the metabolism of Warfarin in the body, thus increasing greatly the risk of hemorrhaging.”  The maintenance dose of Warfarin can fluctuate significantly depending on the amount of vitamin K1 in the diet, thus frequent testing for clotting is required.  Once the highest risk group is removed from studies the touted benefits evaporate.[4]  The need for dangerous, expensive, prophylactic drug intervention also evaporates.”

Alternative to Warfarin (knockoffs)  Acenocoumarol & phenprocoumon unlike warfarin do not need monitoring, such as Phenindione, Atromentin,  dabigatran (Pradaxa) and rivaroxaban.  However since they cannot be reversed like warfarin, there are more fatal bleeds.  FDA report for 2011, much more widely prescribed Warfarin caused 72 deaths, Pradaxa 542 deaths.

Clopidogrel (INN) (Plavix), the most profitable of anticoagulants with 48 million American taking it daily in 2006, and total US sales of over $60 billion by 2010.  Plavix is an oral, thienopyridine class antiplatelet agent that irreversibly inhibits[5] the P2Y12 receptor, an  adenosine diphosphate (ADP) chemoreceptor on platelet cell membranes.  Meta-analysis showed insignificant 8% reduction in major events in non-smokers, & 29% in smokers.  Warfarin & Plavix are effective only for smokers. Unlike warfarin, bleeding cannot be easily reversed.   Because Warfarin and Plavix do not have an antiplatelet effect (the main cause for thrombi), there were several clinical trials with low dose aspirin and Plavix and other trials with Warfarin.  This combination resulted in increased hemorrhaging and the failed to significantly protect from MI more just low-dose aspirin, Cochrane, and the AHA agreed.  Common side effects include hemorrhaging, upper GI discomfort, ulcers, gastritis, rash, osteoporosis, thin skin, and diarrhea; the same for Warfarin. 

 

Direct factor Xa inhibitors ('xabans') are a class of anticoagulant drugs which act directly upon Factor X in the coagulation cascade, without using antithrombin as a mediator.[1] The first of this class is an extracts of Mexican leehes, the second is derived from a tick.  Currently marketed are Apixban, Betrixaban, Edoxaban, Otamixan, and  Rivaroxaban.  Unlike Warfarin they are predictable, but they interact with stains, and there is no way to reverse the anticoagulant effect.  The synthetic pentasccharides inhibitors of factor, Fondaparinux, and Idraparinux, work by antithrombin activation.   

Recommendations:  It is not true that most cases of deep vein thrombosis (DVT) in medical patients can be prevented.”    Aspirin as an antiplatelet  reduces risk of stroke, embolism, and MI[6]; as an anti-inflammatory drug reduces for atherosclerosis with its related strokes and MIs, Alzheimer’s disease, and rheumatoid & osteoarthritis; and because of activation of necrosis factor reduces risk of  cancer risk & increases survival; and these benefits are dose dependent. Thus take 325 mg aspirin daily for prevent clots, or 325 with meals to prevent atherosclerosis & its ischemic events.  Other than a 4% increased long-term risk of gastric ulcer, aspirin is safe.  That 4% is much lower than the 3.43% of major bleeding per year with warfarin.[7]  Risk is greatly reduces with elimination of Helicobacter Pylori bacteria.  When all causes of death are included, anticoagulants don’t save lives, see WARIS study.  JK from 1992 to 1996 took under physician advice eight 325 mg coated aspirin per day for chronic back pain (inflammation) with no heart burn, and has since then takes 325-650 mgs daily, though his blood pressure is 125 over 73 a strong evidence of the lack of atherosclerosis and he is in his 7th decade.  Low dose is ineffective due to tolerance.  Aspirin was the standard arthritis treatment for decades starting at 2.5 grams.  Papers on aspirin:  benefits and history, on cancer, and on atherogenesis.      



[1] Bias average 32%, 2008 NEJM.  74 FDA-registered trials of anti-depressant compared to the raw obtained through the Freedom of Information Act.  Review system is a facade because the raw data is never supplied with the journal submission.  Those who fund the studies own the results. 

[2]  Counter to pharm, stomach bleeds are not more than for other NSAIDS.  Goodman & Gilman 11th Ed. P. 690: “Many clinicians favor the use of other NSAIDs perceived to have better gastro-intestinal tolerability, even though this perception remains unproven by convincing clinical trials.”   

[3]   Like cancer and tobacco, the results take years to become apparent among the low risk group.  There is every reason given the biology behind the process to expect the increased MI for all the NSAIDs, even the low risk group--but for aspirin.  And as stated above the risk varies according to NSAID—which includes the widely advertised Celebrex, whose risk is likely the greatest among the currently available NSAIDs. The other two large PhARMA funded studies are VIGOR 2000 and APPROVe in 2001 for Vioxx.  Both were equal bad; and similar results were had for Celebrex. 

[4]  “We were able to determine the minimal clinical difference of warfarin therapy for the prevention of stroke from the perspective of patients with non-valvular atrial fibrillation. Their differences were much smaller than those that have been implied by some experts.”

[5]  This makes hemorrhaging far more serious than Warfarin which can be treated with vitamin K.  The guidelines require blood work on clotting has driven doctors away from the safer warfarin—more pharma working guideline for their profits. 

[6]  The highest risk group, unstable angina, had a 236% reduction in death, and cardiac event 152%--a 1994 meta-study using 325 mg.

[7] There is a pile of junk science using tricks such as endoscopic search for lesion in the stomach to count as proof of the danger of taking aspirin.  Pharmacology text book, Goodman & Gilman 11th Ed, 2006, p 690: “many clinicians favor the use of other NSAIDs perceived to have better gastrointestinal tolerability, even though this perception remains unproven by convincing clinical trials. 





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Non-technical Summation


Anticoagulants:  They are widely prescribed to prevent or treat thrombosis (blood clots), which can damage the brain (stroke), heart (myocardial infarction), lung (pulmonary embolism), and other organs.  With a few exceptions, they aren’t worth the side effects.  Pharma in junk clinical trials exaggerates the risks of thrombi and the benefits of their anticoagulants; their sales mantra is “safe and effective”.  Pharma’s opinion leaders use these junk clinical trials to instruct physicians in the mandated continuing education classes. Anticoagulants are routinely given to those who undergo major surgery, hospitalized over 2 days, or have arrhythmia (irregular heart beat) because of the higher risk of thrombosis. Once out of the hospital this treatment is normally continued.  They aren’t worth the side effects.  A much, much better choice is to take a 325 mg of aspirin in the morning and another in the evening, and it has many other health benefits (see aspirin above).  At this higher dose it is a better long-term anticoagulant for preventing heart attacks and strokes (by about 50%), while the low dose (thank you pharma) becomes ineffective over time because of tolerance to its antiplatelet effect.  At this dose it also slows are stop atherogenesis.   Aspirin also lowers the risk of most cancers overs 40%, and for those with stage I, ii, or iii cancer it lowers the risk of it becoming metastatic by over 40%.  For these reasons pharma educates doctors about a grossly exaggerated risk of major bleeding, while in fact their patented anticoagulants have a much higher risk.  Long term ulcer risk at high dose is 4%.  Healthful life-style of low carbohydrate-sugar diet and strenuous exercise offers significant benefits because a poor flow of blood is the major causal factor for a thrombi forming, and it lower s blood pressure another causal factor for blood clots. 






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Disclaimer:  The information, facts, and opinions provided here is not a substitute for professional advice.  It only indicates what JK believes, does, or would do.  Always consult your primary care physician for medical advice, diagnosis, and treatment.