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Recent News and Articles on the Keywords: cox-2 inhibitors + heart disease + heart  Related to the article below (Last Update: 7/8/2008)

Death By Prescription
Black Hills Today, SD - Jun 23, 2008
This makes adverse drug reactions to LEGAL medication the third leading cause of death, this following only heart disease (750000 deaths) and cancer (580000 ...
8 drugs doctors wouldn't take
MSNBC - Jun 22, 2008
And yet Celebrex, a COX-2 inhibitor, is still available, even though two other drugs of that class, Bextra and Vioxx, were pulled off the market due to a ...
COX Enzymes and Their Inhibitors: Pitt School of Medicine Hosts ...
WebWire (press release), GA - Jun 16, 2008
... as COX-2 inhibitors; anti-inflammatory pain relievers that held great promise for symptom prevention but were found to increase the risk of heart attack ...
Glossary of Terms and Definitions
National Fibromyalgia Association, CA - Jun 12, 2008
They include aspirin, ibuprofen, and Cox-2 inhibitors, and are used to reduce inflammation and pain associated with illnesses, including, ...
Breaking News from The Plain Dealer
The Plain Dealer - cleveland.com, OH - Jun 10, 2008
Curcumin also is a potential Cox-2 inhibitor, which targets the same inflammatory pathway involved in rheumatoid arthritis. Aggarwal compared curcumin to ...
Source: Google News

COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease -
WA Ray, CM Stein, JR Daugherty, K Hall, PG … - The Lancet, 2002 - Elsevier
... EJ Topol, Risk of cardiovascular events associated with selective COX-2 inhibitors,
JAMA 286 ... drugs and risk of serious coronary heart disease: an observational ...

… anti-inflammatory drugs and risk of serious coronary heart disease: an observational cohort study -
WA Ray, CM Stein, K Hall, JR Daugherty, MR Griffin - The Lancet, 2002 - Elsevier
... a potent endogenous platelet inhibitor, 7 which ... risk of clinically important coronary
heart disease in human ... of the new cyclooxygenase-2 (COX-2)-selective drug ...

Risk of Cardiovascular Events Associated With Selective COX-2 Inhibitors -
D Mukherjee, SE Nissen, EJ Topol - JAMA, 2001 - Am Med Assoc
... Inflammation and coronary heart disease: an overview ... The cyclooxygenase-2 inhibitors:
safety and ... selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib compared ...

Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to … -
PS Sanmuganathan, P Ghahramani, PR Jackson, EJ … - British Medical Journal, 2001 - heart.bmj.com
... Aspirin for primary prevention of coronary heart disease: safety and absolute benefit
related to coronary risk derived from meta-analysis of randomised trials. ...

… -2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart … -
M Mamdani, DN Juurlink, DS Lee, PA Rochon, A Kopp, … - The Lancet, 2004 - Elsevier
... not with new-onset of disease, as did ... of initiating antihypertensive or congestive
heart failure medications ... that selection of one COX-2 inhibitor over another ...

Selective COX-2 Inhibition Improves Endothelial Function in Coronary Artery Disease -
R Chenevard, D Hurlimann, M Bechir, F Enseleit, L … - Circulation, 2003 - Am Heart Assoc
... of cardiovascular events associated with selective COX-2 inhibitors. ... 2 specific
inhibitor, versus ibuprofen ... of serious coronary heart disease: an observational ...

… -2 and Activation of Nuclear Factor-?B in Myocardium of Patients With Congestive Heart Failure -
SCY Wong, M Fukuchi, P Melnyk, I Rodger, A Giaid - Circulation, 1998 - Am Heart Assoc
... The use of specific COX-2 inhibitors in animal models of heart failure will
determine the exact role of the enzyme in this fatal disease. ...

[CITATION] Complications of the COX-2 Inhibitors Parecoxib and Valdecoxib after Cardiac Surgery -
NA Nussmeier, AA Whelton, MT Brown, RM Langford, A … - New England Journal of Medicine, 2005
... surgical-wound events in the pooled COX-2?inhibitor group and ... Congestive heart failure
43 (7.7) 42 (7.6) 32 ... Peripheral vascular disease 47 (8.4) 46 (8.3) 49 ...

COX-2 selective inhibitors cardiac toxicity: getting to the heart of the matter -
NM Davies, F Jamali - J Pharm Pharm Sci, 2004 - ualberta.ca
... that contraindicated using rofecoxib in obvious cases of ischemic heart disease. ...
conflicting body of evidence on the cardiovascular risk with COX-2 inhibitors. ...

… Inflammatory Markers and Endothelial Function in Patients With Ischemic Heart Disease and Raised C- … -
P Bogaty, JM Brophy, M Noel, L Boyer, S Simard, F … - Circulation, 2004 - Am Heart Assoc
... drugs in comparative trials, differences among COX-2 inhibitors, and possible play ...
effect of antiinflammatory therapy in patients with ischemic heart disease. ...

Source: Google Scholar
 
 

How COX-2 inhibitors can lead to heart disease

 
 
Researchers from University of Pennsylvania School of Medicine have found additional evidence that may help explain how selective inhibitors of COX-2 might predispose individuals to heart disease and stroke.

A study, published in Circulation Research, reports that a COX-2-derived fatty substance, a prostaglandin called prostacyclin, controls the blood-vessel response to stresses such as high-blood pressure, thereby further linking COX-2 inhibitors to an increased risk of heart attack or stroke.

This knowledge, along with a growing literature on physiological responses to COX-2 inhibitors, should help in the development of a rational approach to clinical risk management for this class of drugs.

Two randomized trials of COX-2 inhibitors, conducted in 2004, suggested that risk of cardiovascular disease might increase gradually during continued treatment with drugs such as Celebrex ( Celecoxib ) and Vioxx ( Rofecoxib ), even in individuals initially at low risk of the disease.

" The risk of heart attack and stroke became progressively evident during treatment with either Celebrex or Vioxx during the APPROVe and APC trials last year," says Garret FitzGerald, lead author of the study published online last week.
FitzGerald is the director of the Institute for Translational Medicine and Therapeutics at Penn.

These studies were designed to determine whether COX-2 inhibitors in preventing recurrence of colorectal polyps of patients who were at low risk of heart disease.

" While the results of these trials are not conclusive, they are compatible with a gradual transformation of increased cardiovascular risk during continued dosing with either Celebrex or Vioxx," says FitzGerald. " We need to determine how this might occur, and whether we can manage this risk by developing tests that reflect the process."

Earlier animal studies by Penn researchers and others showed that suppression of the protective fat prostacyclin, which is made by COX-2, could predispose individuals to a rise in blood pressure which, in turn, can accelerate hardening of the arteries, or atherosclerosis.

COX-2 inhibitors such as older NSAIDs have been shown to raise blood pressure in people.

In addition, the Penn group has shown in previous studies that shutting down prostacyclin hastens initiation and early development of atherosclerosis.

R. Daniel Rudic, and Derek Brinster, and others in FitzGerald's laboratory, report that COX-2-derived prostacyclin also controls the changes that occur in the muscular lining of blood vessels in response to pressure-related changes in blood flow.

They used two animal models to test their ideas.

In one, they looked at changes in a blood vessel that had been transplanted into mice of a different genetic make-up; in fact, the model mimicks the events of human organ transplant rejection. Here, they found that they had, in effect, removed a brake on the response of the blood vessel to the challenge of transplantation by deactivating prostacyclin by genetically deleting its receptor. The result was that muscle cells proliferated dramatically, which normally reduces the openness of the blood vessel. However, the openness of the blood vessel was not changed, through a process of structural reorganization of the blood vessel called vascular remodeling.

In the second model, they reduced blood flow in arteries in the neck and looked at the downstream effects in the blood vessel. This time, instead of suppressing prostacyclin receptor signaling by genetic deletion, they did so by giving a COX-2 inhibitor. Indeed, they saw the same effect. Cells in the muscular lining of the vessel wall multiplied ( just like in the transplant model ). Additionally, despite the vessel growth caused by the COX-2 inhibitor, openness of the blood vessel was again preserved. This occurred despite lower blood flow caused by the COX-2 inhibitor. Thus, prostacylin may act to remodel blood vessels to preserve adequate blood flow.

" What is really convincing here is how similarly the two models responded and how the genetics of the pharmacological approach to disrupting the effects of COX-2 had the same effect," says Rudic. In further studies, performed in collaboration with Thomas Coffman, of Duke University, FitzGerald's group showed that the consequences of shutting down COX-2-derived prostacyclin could be limited, in part, by removing a receptor activated by thromboxane A2, the fatty product of COX-1 in platelets. This mirrors a similar balancing effect between COX-1 and COX-2, which has been noted in the case of blood clotting, blood pressure, and atherosclerosis. This suggests that suppression of thromboxane with low-dose aspirin could reduce the risk of heart disease if taking COX-2 inhibitors.

These findings suggest that during prolonged dosing with COX-2 inhibitors, several consequences of drug action, a rise in blood pressure, initiation, and early development of atherosclerosis, and now the architectural and functional response of blood vessels to such stress, could all interact in a reinforcing fashion to transform the risk of heart attack and stroke, even in previously healthy individuals.

" We need to determine whether these mechanisms are operative in people, and if so, we should be able to develop tests which reflect this process," says FitzGerald. " This may allow us to detect the small number of individuals at risk of rapidly developing heart disease and stop the drugs before they run into trouble. We could also determine how quickly risk might dissipate on stopping the drugs. Certainly, the development of a rational approach to risk management will be key to giving Celebrex or other COX-2 inhibitors safely, even to healthy patients, for extended periods."

Source: University of Pennsylvania School of Medicine, 2005
 
 
 
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