"In this session we wanted to reach out to clinicians from other specialities and urge them to think beyond the eye, brain and joint, and to be aware of the adverse effects that different drugs can have on the heart," said Dr Frank Ruschitzka from the University Hospital in Zurich, who initiated the Symposium's programme.
Although the cardiovascular risks of non-steroidal anti-inflammatory drugs received intense media attention following the withdrawal of rofecoxib (a COX2 selective inhibitor) in September 2004, surprisingly little attention has been paid to the cardiovascular safety of the older non-selective NSAIDs inhibiting both COX1 and COX2, including paracetamol.
"Nobody has asked the question of what happens with the older painkillers that have been on the market for 40 to 50 years," said Ruschitzka. "People tend to forget that COX2 is also blocked by these drugs." Ruschitzka is now involved in PRECISION, a head-to-head comparator study of celecoxib (a selective COX2 inhibitor) and the non-selective NSAIDs ibuprofen and naproxen in more than 20,000 patients with osteo- and rheumatoid arthritis.
The typical 70-year-old with arthritis, said Ruschitzka, has four to five co morbidities, which in reality means that virtually every arthritis patient has cardiovascular risk factors. "The most important take-home message is don't be afraid of using painkillers, but make sure that your patient's underlying cardiovascular disease is well controlled," he advises.
While it's been known for some time is that tricyclic antidepressants have cardiovascular side effects, including blood pressure changes, conduction disturbances and arrhythmias, and that erythropoetin can result in hypertension, two studies last year flagged up cardiovascular concerns in additional drugs.
Cardiovascular safety of drugs needs to be addressed in proper trials
John Cleland from the University of Hull, UK, reviewed a meta-analysis of the use of glitazone drugs in diabetes. The study, from Rodrigo Lago from the Lahey Clinic Medical Centre in the USA, showed that patients treated with either rosiglitazone or pioglitazone
had a 72% higher risk of congestive heart failure than controls who did not receive the drugs (Lancet 2007; 370: 1129-1136).
Jefrrey Borer from the New York Presbyterian Hospital, USA, looked at a growing body of evidence linking dopamine receptor agonists, used as second-line treatment for Parkinson's Disease, to valve problems.
A study last year by Renzo Zanettini from Istituti Clinici di Perfezionamento in Milan showed that the annual incidence of newly diagnosed cardiac valve regurgitation was 30 per 10,000 patients exposed to pergolide, 33 per 10,000 patients exposed to cabergoline, compared to 5.5 per 10,000 for unexposed patients (NEJM 2007; 356: 39-46).
Drugs which block vascular endothelial growth factor (VEGF), used in age-related macular degeneration and metastatic colorectal cancer, may also have cardiovascular complications. "The worry here is that VEGF is needed for the basic nitric oxide response to cardiac ischemia, and this might disrupt vasodilation and blood flow if these drugs enter the systemic circulation," said Ruschitzka,
The take homes message from the Symposium to pharmaceutical industry is not to market any drugs unless cardiovascular safety has been addressed in proper trials. "As well as being essential for patients, it makes good economic sense too, because otherwise the companies will get their drugs withdrawn," says Ruschitzka.