Page "Celecoxib" Paragraph 16

The Vioxx Gastrointestinal Outcomes Research ( VIGOR ) trial presented a five-fold increase in atherothrombotic cardiovascular events associated with rofecoxib compared to naproxen.

Although, the Celecoxib Long-Term Arthritis Safety Study ( CLASS ) did not present an increase in occurrence of such events, many experts believe that the risk associated with rofecoxib long-term use also applies to celecoxib based on the pharmacology in three distinct mechanisms.

It is suggested that prostacyclin ( PGI < sub > 2 </ sub >) inhibition with relatively unopposed platelet-derived thromboxane ( TxA < sub > 2 </ sub >) generation may lead to thrombotic risks.

PGI < sub > 2 </ sub > from endothelial cells by COX-2 catalysis has anti-aggregating, anti-proliferative, and vasodilating properties.

Conversely, TxA < sub > 2 </ sub > from platelets maintain vascular homeostasis by irreversible platelet aggregating, vasoconstricting, and smooth muscle proliferating properties.

The imbalance of PGI < sub > 2 </ sub > may promote TxA < sub > 2 </ sub > thrombosis.

In addition, COX-2 selective inhibitors can elevate blood pressure by allowing a normal amount of the vasoconstrictor, TxA2, and a stark decrease in the levels of the vasodilator, PGI < sub > 2 </ sub >.

Furthermore, a third postulate for promoting atherothombotic events includes that the upregulation of COX-2 plays a key role in cardioprotection of the last phase of ischemic preconditioning.

Due to the controversy, it is advised that prescribers use caution when prescribing celecoxib and present rational care plans that demonstrate a clear indication for the medication.