Although their study methodology precluded solid evidence that selective cyclo-oxygenase-2 inhibitors increase the risk of heart attack, a series of analyses published by physicians at the Cleveland Clinic Foundation has highlighted the need for controlled clinical studies to evaluate the cardiovascular effects of COX-2 products.

COX-2 inhibitors were designed to provide anti-inflammatory properties without gastrointestinal upset or ulceration. This is done by inhibiting COX-2 enzymes, which are expressed primarily in inflamed tissues, without affecting Cox-1 enzymes that are present in many tissues and play a gastroprotective role.