I can't keep all your colors straight when I reply so forgive my wandering from blue to grey to black...
ofonorow wrote:Interesting interpretations. More than one Plavix trial was stopped years ago, and since they were never published, these reports are hard to find. (I'll keep looking.)
Do you deny that more than one trial was curtailed early?
As I said, I am not aware of more than one. If you can find them I'm happy to read them. If any are trials on people with stents post-MI, I'd sure like to know about them, believe me.
The reasons given for ending the clinical trial in the news reports were that the Plavix groups were experiencing higher mortality w/r to the placebo group. (There may have been bleeding or other issues.)
They stop the trial, they know the drug is dangerous to give to that type of patient, and it won't be prescribed for them. Plavix reduces mortality in certain people. I have no doubt it's bad for others. I started this conversation to determine whether it might be bad for Larry and why you would comment to him about studies that would appear to have no relevance to his situation.
It doesn't matter to me all that much why Plavix was apparently killing patients, but I may be missing something. If you feel comfortable with the distinction about the patient types, that is your opinion.
I'd be very uncomfortable NOT making the distinction. We are all patient types, like it or not. Someone with primary hyperoxaluria could rightly claim megadosing Vitamin C was dangerous... for them. Drinking water can be dangerous if you're already overhydrated. People with life-threatening anaphylactic reactions to nuts haven't frightened me away from eating almonds. Thalidomide has horrific results in pregnant women but is used effectively on leprosy patients. If you don't draw distinctions between different people taking Plavix I think you are missing something, yes.
No drug is meant for everybody to take. That's why they have contraindications. It's why we have prescriptions. It's an attempt to keep people who don't need a drug or are at risk from it away from it.
I'm not sure what your point is here.
I'm in favour of warnings on the labels and updating them whenever something new is learned. I got warnings from 3 doctors + a pharmacist before I even got to the label. I like that; nobody can make an informed choice if they're not informed.
If I kept an eye on all the lawsuits I'd have no time to go outside, but I'm sure some people have a case and some don't. If some people shouldn't have taken Plavix and suffered harm from it, the fault may lie with the drug company, or with the doctor who prescribed it, or even with the patient (if they didn't give an accurate history or misused the drug.) But the existence of lawsuits, on its own, really doesn't mean anything. Wherever there is money there will be people suing. It's encouraged by whopping settlements for things like coffee being too hot.
I'll keep trying to find information on the trials that were halted.
Okay.
p.s. Here is another trial that was halted, supposedly because of a bankruptcy.
http://www.theheart.org/article/1007145.doCOGENT trial resultsAs previously reported by heartwire, the COGENT trial was stopped early after the trial sponsor, Cogentus Pharmaceuticals (Palo Alto, CA), declared bankruptcy. The trial was a phase 3 study testing the company's combination product, known as CGT-2168, in patients requiring clopidogrel for at least 12 months, typically following non-ST-segment-elevation ACS, STEMI, or stent implantation. CGT-2168 was to be a once-daily pill that combined 75-mg clopidogrel with 20 mg of the gastroprotectant omeprazole.
The study was stopped with only 3627 patients enrolled out of the roughly 5000 investigators had hoped to recruit. Mean follow-up was 133 days (and a maximum of 362 days), with 136 adjudicated CV events and 105 adjudicated GI events. An additional 14 events have not yet been adjudicated, Bhatt noted.
Showing survival data out to 390 days, Bhatt reported that
67 cardiovascular events—a composite of CV death, nonfatal MI, CABG or PCI, or ischemic stroke—occurred in the placebo group and
69 in the omeprazole group, with superimposable event curves. For the end points of MI alone and revascularization procedures alone, event curves once again were identical.
In analyses taking into account baseline variables or medical history, there was no signal of increased cardiovascular events for patients treated with omeprazole in any subgroup. By contrast, looking just at GI events (upper-GI bleeding, symptomatic upper-GI bleeding, pain of presumed GI origin with underlying multiple erosive disease), researchers found that event rates were significantly higher in patients
randomized to placebo. Randomized to placebo?
Yes, GI events were higher in the placebo group without omeprazole.
Everyone took Plavix. The placebo group refers to Plavix by itself, you understand that right? The treatment group was Plavix + a stomach-protecting add-on.
The study was meant to find out 2 things: whether Plavix + omeprazole would reduce gastrointestinal bleeds/pain caused by the Plavix, but mainly whether the omeprazole might blunt the beneficial effects of the Plavix (interfere with absorption, etc.) They were concerned that if they added a gastrointestinal protectant to the Plavix, the number of heart attacks etc. would rise.
The cardiovascular events stayed the same in both groups, so the omeprazole was not affecting the Plavix working.
The bankruptcy is interesting because prior to this study, the media ran with a story that such 'combined therapy' would keep the clopidogrel from working properly, based on observational data, before a randomized placebo controlled trial was done. And the FDA issued statements that the combination might be dangerous. It seems the company claims this negative publicity is what sunk their drug. I wouldn't blame them for being pissed when they do a proper study showing the concern was baseless.
"...a panel of experts talked over one another to implore reporters to do a better job at differentiating between randomized controlled trial results and observational studies. The latter have been widely reported in the media—including on theheart.org—and have been largely responsible for raising concerns that concomitant PPI therapy, taken to minimize gastrointestinal side effects, might blunt antiplatelet effects of clopidogrel. Both the European Medicines Agency (EMEA) and the FDA have, in the past year, issued public statements on a possible adverse interaction between clopidogrel and PPIs.
"No more headlines about observational studies on theheart.org. Please," Dr Shamir Mehta (McMaster University, Hamilton, ON) scolded. "This is it. This is the real thing. This shows you how you can be completely misled by observational data, and those data can [lead] to opinions that are blown way out of proportion, to the point where health authorities change the labeling of these agents without randomized trial evidence. Now we have a randomized trial that shows this is not the case."