Cardiovascular risk profile of antirheumatic agents in patients with osteoarthritis and rheumatoid arthritis.
Several new drugs have become available for the treatment of patients with osteoarthritis and rheumatoid arthritis (RA). These agents include selective cyclooxygenase (COX)-2 inhibitors, leflunomide and anti-tumour necrosis factor (TNF)-alpha antagonists. COX-2 inhibitors have a more favourable gastrointestinal adverse effect profile than conventional non-steroidal anti-inflammatory drugs (NSAIDs). However, the COX-2 inhibitors are also associated with hypertension, oedema and congestive heart failure, the well-known adverse effects of conventional NSAIDs. Patients with treated hypertension should be monitored regularly when conventional NSAIDs or COX-2 inhibitors are administered. At present, there is a considerable debate regarding the risk of cardiovascular events with the COX-2 inhibitors. The available literature gives no unequivocal answers. This matter can only be solved by an appropriate trial assessing the cardiovascular risk of these agents. Patients with RA appear to have an enhanced cardiovascular risk which might be related to an unfavourable lipid profile. Corticosteroids induce hypercholesterolaemia in patients other than those with RA. It was recently shown that total and high-density lipoprotein (HDL) cholesterol were low in patients with RA who had a high disease activity. Contrary to the expectation, combination therapy with prednisolone rapidly improved the atherogenic index (total/HDL cholesterol). Ongoing studies investigating this topic are underway. It is not known to what extent corticosteroids induce hypertension in patients with RA. Hence, we advocate blood pressure control for these patients. A small percentage of patients with RA develop hypertension when taking leflunomide, and no other serious cardiovascular adverse effects have been reported in the literature. Blood pressure monitoring is recommended especially in the first months of treatment. TNFalpha antagonists are contraindicated in patients with RA who have congestive heart failure. No specific cardiovascular adverse effects have been reported with the use of these agents in the non-cardiovascular compromised patient. TNFalpha antagonists are the most powerful anti-inflammatory drugs presently available. As inflammation plays an important role in RA as well as in cardiovascular disease and, in view of the increased cardiovascular risk in RA, it is tempting to expect that suppression of inflammation ultimately will lower the cardiovascular morbidity and mortality in patients with RA.
Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands. m.nurmohamed@janvanbreemen.nl
Michael T
MT
Nurmohamed
Vokko P
VP
van Halm
Ben A C
BA
Dijkmans
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use; D000077339:Leflunomide; D008565:Membrane Proteins; D010003:Osteoarthritis / Q000188:drug therapy*; D011451:Prostaglandin-Endoperoxide Synthases; D018570:Risk Assessment; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007555:Isoxazoles; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000077339:Leflunomide