Why do cox 2 inhibitors cause heart attacks

In addition to recognizing the cardiovascular risk profile and dose relationship of each NSAID, it is also important to review the evidence with respect to the timing and duration of therapy. The primary outcome of the study is the first occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke. Cardiovascular, GI, and renal side effects as well as symptomatic relief will be assessed in the study. The trial is set to be completed in September and may provide additional evidence for the use of NSAIDs in patients with cardiovascular risk.

In , the American Heart Association AHA addressed the concern that selective COX-2 inhibition may potentiate a cardiovascular event in patients who are at an increased risk. The AHA states that physicians and patients must weigh the risks and benefits of each agent before choosing a treatment plan for pain relief.

Patients should be treated only for the shortest amount of time and with the lowest dosage of drug necessary to gain symptom relief. A stepwise approach is suggested, beginning with the agents that have the lowest associated cardiovascular risk and moving to the agents with higher risk if treatment failure occurs. Non-NSAID products, such as acetaminophen or nonacetylated salicylates, are the preferred agents in patients with high cardiovascular risk.

If pain control is not established with nonselective NSAIDs, the next trial should be with an agent that is semiselective for COX-2, such as meloxicam or diclofenac. Finally, if all the above treatments have failed, the patient may consider treatment with the selective COX-2 inhibitor celecoxib.

Celecoxib use in patients at risk for thrombotic events should be reserved for patients who have no other appropriate alternatives. Concurrent use of nonselective NSAIDs with aspirin may decrease the cardioprotective profile normally seen with aspirin use. This is due to competitive inhibition of the receptor-binding site of the COX-1 enzyme. During treatment with NSAIDs, patients should be closely monitored for increases in blood pressure, signs of edema, decreasing renal function, and GI bleeding.

If any of these adverse effects occur, a decrease in dose or a change in drug may be warranted. With each patient case the risks and benefits of treatment should be considered before beginning any one agent.

When initiating any NSAID in a patient with high cardiovascular risk, it is important to monitor blood pressure. Concurrent use of NSAIDs with antihypertensive medications has been associated with a decrease in the blood pressure lowering effects of the antihypertensive therapy.

The significance of pharmacist-patient communication is crucial in informing patients about the risks associated with use of NSAIDs. These situations provide an opportunity for pharmacist intervention to educate patients on the risk and inform them of preferred alternative therapies for pain management, such as acetaminophen, capsaicin, and other topical products.

Notably, healthcare professionals should keep in mind that for patients with arthritis or other comorbid conditions who require NSAID therapy, naproxen appears to be the safest from a cardiovascular perspective.

The cardiovascular risk with NSAIDs appears to increase as the dosage and duration of therapy increase. Patients receiving NSAID therapy should be advised to use the lowest effective dose for the shortest duration of time. At a Glance Accessed November 25, Osteoarthritis Health Center. Pharmacotherapy Principles and Practice.

Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med.

Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol. An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs. Am J Cardiol. Cardiovascular risks of nonsteroidal anti-inflammatory drugs in patients after hospitalization for serious coronary heart disease. Circ Cardiovasc Qual Outcomes. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis.

Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. Public Health Advisory. April 7, Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction.

Eight placebo-controlled, randomized trials, performed to find new uses of these drugs, showed that they posed a cardiovascular hazard, similar in magnitude to that resulting from being a smoker or a diabetic, notes FitzGerald. Arguments against the proposed mechanism were threefold. First, it was proposed that COX-2 didn't exist under normal circumstances in the blood-vessel lining and PGI-M came from some other source.

The kidneys were suggested as the source by some researchers. Second, even if blood-vessel prostacyclin was blocked, other protective mechanisms, especially formation of nitric oxide NO would take over. And third, although NSAIDs elevate blood pressure, it was proposed that this observation was unrelated to COX-2 and treating high blood pressure would deal with the problem. FitzGerald's group has now "closed the loop" with its earlier clinical studies and answered these questions in a paper just published in Science Translational Medicine.

In it, they confirm that COX-2 is expressed in cells lining blood vessels and that selectively removing it predisposes mice to blood clotting and high blood pressure. Indeed, the lost NO may not be the only step that magnifies the effects of losing prostacyclin. In a second paper, published in April , in the Proceedings of the National Academy of Sciences, FitzGerald's group shows that arachidonic acid, the fat broken down by COX-2 to make prostacyclin, can be shunted down another pathway to make a new series of dangerous fats called leukotrienes when COX-2 is disrupted.

Clinical studies have shown that those most at risk from COX-2 inhibitors are patients who already have heart disease. However, the Penn group now suggests broader implications. Here, the group resolves one aspect of the controversy, showing that COX-2 disruption causes hardening of the arteries in mice.

This result is provocative because randomized trials of Vioxx and Celebrex in patients at low risk of heart disease detected an increase in heart attacks after patients had been taking the drugs for more than a year. These current Penn studies raise the disturbing prospect that heart-healthy patients taking NSAIDs for prolonged periods might be gradually increasing their risk of heart attacks and strokes by progressively hardening their arteries.

This risk of hardening of the arteries was diminished in mice by reducing leukotriene formation, via blocking a critical protein called the 5-lipoxygenase activating protein, or FLAP.

Inhibitors of FLAP are already in trials in humans to see if they work in asthma. Note: Content may be edited for style and length.

Science News. Funk, and Garret A. ScienceDaily, 2 May