Blood thinners and acetaminophen
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PLAVIX causes major stomach bleeds


In 2006 48 million American’s were taking it daily

Besides going after aspirin, they sometimes recommend the use of aspirin in combination with other drugs.  Such often isn’t warranted on the basis of journal articles which have been shown consistently to have a very significant positive bias (what else would you expect for research run by market departments).  In the landmark study below Plavix (Clopidogrel) and aspirin failed to be significantly better than aspirin and placebo (and very likely the combination was worse because of marketing bias.  When reading journal articles remember that (a) the editors do not see the raw data, and (b) that the drug companies provide over 90% of the advertising revenue for that journal.  For my library on aspirin:

The disconcerting fact is that the sales persons for Bristol-Myers will be telling receptive doctors that the combination is better than Plavix alone when the difference is only insignificant.  They will tell these care givers that they should give Plavix to their patients who are on aspirin (they won’t tell them that the patient who are on Plavix to add aspirin).  Secondly they won’t tell the patient of the modest increase in gastrointestinal bleeds (which in other study come out much higher) or that Plavix greatly increase the risk of a hemorrhagic stroke—which was conveniently not included in this study. 

Generic drug name: clopidogrel (kloh PID oh grel)
Brand name(s): PLAVIX (Bristol-Myers Squibb Company)

FAMILY: Adenosine Diphosphate Blockers, Blood-clotting Inhibitors

Landmark study fails to show a significant benefit for taking Plavix with Aspirin New England Journal of Medicine 3/12/2006 at 354:1706.17

Clopidogrel and Aspirin versus Aspirin Alone

for the Prevention of Atherothrombotic Events



Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied

in a broad population of patients at high risk for atherothrombotic events {blood clot of a coronary artery that supplies oxygen to the heart muscle}.


We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes.


The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P = 0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P = 0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P = 0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P = 0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P = 0.01). In the subgroup with clinically evident

atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P = 0.046).


In this trial, there was a suggestion of benefit with clopidogrel treatment in patients

with symptomatic atherothrombosis and a suggestion of harm in patients with multiple

risk factors. Overall, clopidogrel plus aspirin was not significantly more effective

than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from

cardiovascular causes. ( number, NCT00050817.)


Very likely the results would be much better if the aspirin given with the placebo was the standard dose of 325 mg.  I have strongly recommended this higher does because of the ability to very significantly reduce cancer risk and increase cancer survival, which is dose related.    The method by which aspirin accomplishes this is through the body’s mechanism of apoptosis (the destruction of abnormal cells) which it enhances. 

The difference between the two groups is a 0.5% lower incidence during the period of the study (28 months) of major atherothrombotic event. This translates into 1 less atherothrombotic event for every 200 taking the combination therapy.  Moreover in another study there was an increased major bleeding event (requiring a transfusion of 2 or more pints of blood) 1% of those on Plavix compared to aspirin alone.  SIDE EFFECTS AND COST MAKE IT CLEAR THAT ASPIRIN ALONE IS THE PREFERRED TREATMENT. 

The marketing  department of Bristol-Myers Squibb runs with what every positive crumb they can find, such as that in one study Plavix was slightly superior for aspirin for the first 30 day, but not thereafter,




Safety Warnings For This Drug: [top]

Because the retail cost of clopidogrel is at least 100 times greater than the cost of aspirin and is no better than aspirin in preventing a second heart attack or stroke, its use should be limited to those who cannot take aspirin. The long-term use of clopidogrel in the management of patients with acute coronary syndromes is unclear. Long-term clopidogrel may be no better than aspirin.

BOXED WARNING {FDA required on drug package}

  • Warn about reduced effectiveness in patients who are poor metabolizers of PLAVIX. Poor metabolizers do not effectively convert PLAVIX to its active form in the body.
  • Inform healthcare professionals that tests are available to identify genetic differences in CYP2C19 function.
  • Advise healthcare professionals to consider use of other anti-platelet medications or alternative dosing strategies for PLAVIX in patients identified as poor metabolizers.1


Also, a New England Journal of Medicine study published on April 20, 2006, found that clopidogrel, when given in combination with aspirin, was overall no more effective than aspirin alone in reducing the rate of heart attacks, strokes, or deaths from cardiovascular causes.5  {SEE ARTICLE ABOVE}

In a study examining the management of acute coronary syndromes, clopidogrel was found to be marginally better than aspirin by only 2.1 percent. However, there were statistically significantly more patients with major bleeding episodes (defined as needing a transfusion of at least two units of blood) in those taking clopidogrel. In this study, 1 percent more patients taking clopidogrel had a major bleeding episode compared to the aspirin-treated patients, but there was no statistical difference between those taking clopidogrel or aspirin in regard to episodes of life-threatening bleeding.6

In 2009 the FDA issued information concerning the use of clopidogrel and omeprazole. According to the FDA release, the concurrent use of clopidogrel and omeprazole resulted in a reduction in the effectiveness of clopidogrel. The FDA release also stated that separating the administration time of the dose of each drug did not reduce the harmful interaction of this therapy.

According to the FDA, “Other drugs that are expected to have a similar effect and should be avoided in combination with clopidogrel include: cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, and ticlopidine.” 10

Bleeding ulcers

Research published in the January 20, 2005, New England Journal of Medicine found “an astonishingly high rate of bleeding ulcers” in patients taking clopidogrel (PLAVIX) compared to patients taking plain aspirin plus the antiulcer/heartburn drug esomeprazole (NEXIUM). No safety advantage was found for clopidogrel over aspirin plus esomeprazole in ulcer bleeding. (See complete article from March 2005.)

Delaying Generic Competition — Corporate Payoffs and the Future of Plavix

Miriam Shuchman, M.D.

N Engl J Med 2006; 355:1297-1300September 28, 2006

This article has no abstract; the first 100 words appear below.

In August, pharmacies began selling a cheaper, generic version of the blockbuster antiplatelet agent Plavix (clopidogrel). This was good news for patients with cardiac disease or stroke who cannot afford to buy the medication at more than $4 a day. But to Bristol-Myers Squibb and Sanofi-Aventis, who produce and market the drug, it was a financial disaster. Plavix is the world's second-best-selling drug — 48 million Americans use it on a daily basis — and with sales of more than $6 billion last year, it accounts for about 30 percent of Bristol-Myers's total earnings. In an effort to keep the . . 

For JK’s library on aspirin