Rationale for testing the cardiovascular risk for patients with COX-2 inhibitors on the basis of biomarker NT-proBNP

Abstract

Owing to the selective inhibition of PGI2 synthesis, treatment with COX-2 inhibitors constitutes a potential risk for the increased occurrence of thrombotic cardiovascular incidents and of the first-time occurrence or a deterioration in pre-existing heart failure. Elderly patients, particularly those with a history of ischemic heart disease, hypertension or heart failure, are at risk. One key indication for selective COX-2 inhibitors is the chronic treatment of patients suffering from rheumatoid arthritis or osteoarthritis. However, these patients have an excess cardiovascular mortality, which relates particularly to cardiovascular incidents or heart failure. The use of nonselective antiphlogistic drugs and COX-2 inhibitors is associated with a higher potential risk in these patient groups. In essence, more than 80 million patients worldwide were treated with rofecoxib up to its voluntary withdrawal. The high number of patients who are still being treated with COX-2 inhibitors or for whom the use of COX-2 inhibitors is planned justifies the use of a biochemical marker which, as a screening instrument, is initially designed to recognize the patients who are "ill" despite the lack of symptoms. In asymptomatic patients with NT-proBNP levels below the cut-off, high-risk patients require further work-up. Recognition of these risk factors is easily accomplished considering the case history and the results of an established cardiovascular risk score (e.g. PROCAM score). These risk patients should then also be referred for intensive diagnostic work-up. On the other hand, symptomatic patients or those with high NT-proBNP levels should primarily be referred for more extensive cardiovascular diagnosis before a decision is taken concerning the use of COX-2 inhibitors. As an integral part of this extensive work-up the determination of NT-proBNP can help to improve the accuracy of diagnosis and prognostic assessment. With the exception of patients showing symptoms of an unstable coronary heart disease, imminent cerebral ischemia, uncontrolled arterial hypertension or decompensated heart failure, the use of a COX-2 inhibitor is possible provided special caution is exercised. Termination of treatment is advisable if there is a clinical deterioration of specific symptoms or signs in those patients (product information). Follow-up with NT-proBNP (monitoring) can be helpful in detecting imminent cardiac decompensation at an earlier stage in order to take suitable countermeasures.