Saturday, September 15, 2007

New Evidence on COX2 and the heart

We have all heard of the COX2 controversy not so long ago, when the FDA asked MSD to withdraw their (then new) COX2 agent VIOXX from the shelves in USA, when they saw an increase rate of heart attacks in patients who were using VIOXX chronically for their joint pains. There was some suggestions on this in the VIGOR study. Post market surveillance by FDA also seemed to support this fear. Of course, in defense, MSD countered that there was although there was a trend, they explained that the population who were taking VIOXX were also the epopulation who were likely to have haert attacks, and so it may just be the population cohort. Clinical explanation were lacking to support the FDA. Pfizer, who also had two COX2 decided to voluntarily withdraw BEXTRA (another COX2) but continued to sell their CELEBRAX, saying that in their CLASS trial, they did not notice any increase in heart attacks. When we look at the CLASS study, those who were taking CELEBRAX were, fortunately for the patients also taking aspirin. This must have protected them, thereby counteracting the pro-thrombotic effects of the COX2. Many of us do believe that COX2 agents are pro-thrombotic. Well, we now have some evidence. Dr M Gnosh and investigators at the Connecticut Heart Center, studied the pro-thrombotic effects of COX2 in mice. Their findings were published in the latest on-line version of the J. of Experimental Medicine. They notice that mice given COX 2 had a reduction in PPAR delta, which in turn allowed a higher level of TF ( tissue factor ), which was pro-thrombotic, at the endothelial wall. Just to recollect that in normals, COX2 stimulates the endocannabinoid system to release PPAR delta, which in turn reduces TF on the endothelial wall, preventing platelet aggregation and thrombosis. With COX2 inhibitor use, the COX2 inhibitor reduces the PPAR delta release by their effects on the endo-cannabinoid system, thereby allowing greater release of TF on the endothelial wall, and so promoting thrombosis. TF inhibitors does reverse this effect. Obviously much more work needs to be done. If this piece of evidence is reproduced, then we would have a good explanation on what FDA is talking about. Alas, the FDA is proven correct on this one.

1 comment:

Steven said...

Steven said...
Celebrex may be helping my DES stent inflammation a little bit... still testing it on myself...I am suffering from ACS literally every day for 5.5years as a result of a DES drug eluding coronary stent... I am finding that Celebrex is a bit helpful (suggested by head of a cath lab at different hospital than the one mine was placed in) ... and looking for natural methods, top fish oil, herbs etc., anyting to stop this daily severe and dangerous vascular inflammation and pain. It has been a 10 of pain almost every day since the day after I had a large Cypher DES placed in my Osteum of LAD. Also thousands are all over the web complaning about significant post stent chest pain/angina with completely patent DES stents... really getting quite common. Every middle aged man I have met with a DES has the problem like mine. Older people don't complain, because the doctors tell them "it your heart", you are old and sick, or "not right in the head". There are also dozens of articles and studies on post stent pain, inflammation, allergy, especially for the DES... yet interventionists are still in (monetary) denial... Surgeons however are now speaking up for the first time about stents (especially DES) heated arguments are going on in hospitals. The DES is junk, dangerous... careful ballooning, followed by rest and the many available medicines and strict change in diet, untimately later excercise, all far preferable... and if need be, a bare metal in the most dire of proven cases. Otherwise forget the DES, until they invent something that does not first "harm" the patient... I am suffering every day, and have tried everything to no avail... some courageous interventionists are suggesting Celebrex, with increasing aspirin; next choice Prednisone (a dangerous choice, but what else to do) by some interventionists. Some articles and studies on the various "treatments" are on the web. But most interventionists are just blowing off the patients. Some other interventionists however are also suggesting antihistamines, and various immune altering drugs, but this is dangerous. Antihistamines did not help me at all... good idea though... only Celebrex helps me, and only a little bit, at 400mg per day. I am left to experiment on myself as many thousands of others are, suffering from "stent-osis"... while the top doctors just give nice speeches in nice places... stent-osis is far worse than arteriosclerosis, as there in apparently nothing you can do to cure stent-osis, not vigorous exercise, nothing, and the vessel just gets more inflammed the more you exercise or do anything. Bypass and removal of stent becomes all the more dangerous with stents in the way, having been inflammed in the vessel, etc. Calcium Channel blockers, Ace block/inhibitors/statins/ Plavix, all useless, tried them all... nothing stops the vascular/stent inflammation, except Celebrex, and only a tiny bit. All drugs have been useless... post if you have had success with a remedy, or if you have used celebrex for anything for any extended period of time... My advice: never, ever, ever allow any doctor to put a DES in you heart, ever...

10:13 PM