Medicine Hat News - Common drug combo used in heart patients could cause recurrent heart attacks
The findings suggest somewhere between five and 15 per cent of all recurrent heart attacks are caused by the fact that patients are taking a combination of the anti-clotting drug Plavix (clopidogrel) and an gastric acid-reducing medication called a proton pump inhibitor or PPI.

Many, though not all, drugs in the PPI class block the ability of the liver to activate Plavix. When taken in combination, they essentially negate or "turn off" the blood thinning drug, said Juurlink, who did the research with colleagues at the Institute for Clinical Evaluative Sciences.
How pills, tablets, capsules affect us
Family Health - A Gene Variation + Plavix May Lead To Additional Serious Heart Problems | Health News
Heart attack patients who are taking Plavix may want to rethink their drug treatment if they have a particular gene variation. Younger heart attack patients who carry a specific gene variation and take this anti-clotting drug are more prone to additional serious heart problems. Some patients have not done well with Plavix treatment and doctors were not really sure why. Now, they may have their answer.
FDA Considers Updating Label For Anticlotting Drug Plavix
Amid recent studies showing the anti-clotting drug Plavix may not be effective for 30% of cardiac patients, federal regulators are considering updating the drug's label to include information on genetic factors that could interfere with the medicine.

In the past several years, medical literature on Plavix has shown heart patients suffered cardiac events even though they were taking the drug regularly. Researchers and doctors weren't sure of the cause.

Last week, three studies - two in the New England Journal of Medicine and one in the Lancet - identified a genetic abnormality in some heart patients that could interfere with their liver's ability to completely process Plavix in their bloodstream.

All the studies agree something is interfering with Plavix's metabolization via a path in the liver called 2c19. But they differ on how widespread the problem is. Two of the studies suggested the drug was less effective in about 30% of the population that has the mutated gene from either one parent or both, while one study indicates the drug is only less effective in the 5% of the population that has the gene from both parents.
Gene Ups Risk for Those on Blood-Thinner Plavix - washingtonpost.com
A gene variation can make younger heart attack patients more prone to another heart attack, death or other heart problems if they receive the anti-clotting drug Plavix, researchers report.

Perhaps a little misleading. The idea is that if you have this genetic variation, the anti-clotting drug Plavix is less/non-effective. In young patient who are depending on this treatment for many years, this potentially increases their risk of heart attack significantly. So the problem hits young and old, but more relevant to younger patients given the time they will be on the drug, thinking it's helping with anti-clotting when it really isn't.
Use of Aspirin Versus Clopidogrel Plus Aspirin Aft...[Clin Appl Thromb Hemost. 2008] - PubMed Result
Aspirin and clopidogrel together reduce the risk of recurrent thrombosis-related events in patients with acute coronary syndromes or stent revascularization and may reduce thrombosis-induced saphenous vein graft failure. In this retrospective, observational study, 4297 patients were assigned to 2 groups after coronary artery bypass graft surgery, based on medications prescribed at hospital discharge: aspirin only (n = 3318) or aspirin plus clopidogrel (n = 979). At 4-year follow-up, unadjusted survival was similar between the 2 groups (aspirin-clopidogrel, 87.9% vs aspirin-only, 88.8%, P = .43). After statistical adjustment using Cox regression analysis, dual anti-platelet therapy at hospital discharge was not associated with improved survival (odds ratio 1.055, 95% confidence interval 0.7-1.4, P = .72). In propensity score-based, case-matched populations (962 patients each), similar results were obtained (odds ratio 0.996, 95% confidence interval 0.7-1.4, P = .98). In our study population, aspirin plus clopidogrel did not provide survival benefit over treatment with aspirin alone in 4 years after coronary artery bypass graft surgery.
PLAVIX - clopidogrel bisulfate tablets
The CAPRIE trial was a 19,185-patient, 304-center, international, randomized, double-blind, parallel-group study comparing PLAVIX (75 mg daily) to aspirin (325 mg daily). The patients randomized had: 1) recent histories of myocardial infarction (within 35 days); 2) recent histories of ischemic stroke (within 6 months) with at least a week of residual neurological signs; or 3) objectively established peripheral arterial disease. Patients received randomized treatment for an average of 1.6 years (maximum of 3 years).

The trialís primary outcome was the time to first occurrence of new ischemic stroke (fatal or not), new myocardial infarction (fatal or not), or other vascular death. Deaths not easily attributable to nonvascular causes were all classified as vascular.
As shown in the table
PLAVIX (clopidogrel bisulfate) was associated with a lower incidence of outcome events of every kind. The overall risk reduction (9.8% vs. 10.6%) was 8.7%, P=0.045. Similar results were obtained when all-cause mortality and all-cause strokes were counted instead of vascular mortality and ischemic strokes (risk reduction 6.9%). In patients who survived an on-study stroke or myocardial infarction, the incidence of subsequent events was again lower in the PLAVIX group.

Although the statistical significance favoring PLAVIX over aspirin was marginal (P=0.045), and represents the result of a single trial that has not been replicated, the comparator drug, aspirin, is itself effective (vs. placebo) in reducing cardiovascular events in patients with recent myocardial infarction or stroke. Thus, the difference between PLAVIX and placebo, although not measured directly, is substantial.

My conclusions - Plavix yielded 0.8 percent benefit over aspirin.
PLAVIX - clopidogrel bisulfate tablets
Dose dependent inhibition of platelet aggregation can be seen 2 hours after single oral doses of PLAVIX. Repeated doses of 75 mg PLAVIX per day inhibit ADP-induced platelet aggregation on the first day, and inhibition reaches steady state between Day 3 and Day 7. At steady state, the average inhibition level observed with a dose of 75 mg PLAVIX per day was between 40% and 60%. Platelet aggregation and bleeding time gradually return to baseline values after treatment is discontinued, generally in about 5 days.
PLAVIX - clopidogrel bisulfate tablets
Biotransformation of clopidogrel is necessary to produce inhibition of platelet aggregation, but an active metabolite responsible for the activity of the drug has not been isolated. Clopidogrel also inhibits platelet aggregation induced by agonists other than ADP by blocking the amplification of platelet activation by released ADP. Clopidogrel does not inhibit phosphodiesterase activity.

Clopidogrel acts by irreversibly modifying the platelet ADP receptor. Consequently, platelets exposed to clopidogrel are affected for the remainder of their lifespan.
Side Effects of PLAVIX from PLAVIX.com...
In clinical trials, the most common side effects were severe itching (pruritus), a severe rash characterized by the appearance of purplish spots or patches (purpura), diarrhea, and rash.

If you have a stomach ulcer or other condition that causes bleeding, you should not use PLAVIX. When taking PLAVIX alone or with some other medicines including aspirin, the risk of bleeding may increase so tell your doctor before planning surgery.

If you develop fever, unexplained weakness or confusion, tell your doctor promptly as these may be signs of a rare but potentially life-threatening condition called TTP, which has been reported rarely, sometimes in less than 2 weeks after starting therapy. Other rare but serious side effects may occur.

If you have a stomach ulcer or other condition that causes bleeding, you should not use PLAVIX. When taking PLAVIX alone or with some other medicines including aspirin, the risk of bleeding may increase so tell your doctor before planning surgery.
Plavix (Clopidogrel Bisulfate) drug description - FDA approved labeling for prescription drugs and medications at RxList
"Plavix (clopidogrel bisulfate) is an inhibitor of ADP-induced platelet aggregation acting by direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex."
Plavix side effects (Clopidogrel Bisulfate) and drug interactions - prescription drugs and medications at RxList
Clopidogrel - Wikipedia, the free encyclopedia
Clopidogrel, generic term for Plavix.

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