A new analysis from the Nurses Health Study published online this week in the American Medical Association journal Hypertension (2005; 46 :500) shows paracetamol almost doubles the risk of developing hypertension among women taking more than 500mg daily over five years, irrespective of age. Risks of high blood pressure were also increased among women who took 400mg of ibuprofen daily - by almost 80% if they were over 50 and by 60% if they were younger than 50. Aspirin did not increase risks of hypertension at any age.

The study conducted by renal specialists Drs John Forman and Gary Curhan of Brigham and Women’s Hospital, Boston and Dr Meir Stampfer of Harvard School of Public Health looked at the development of hypertension in more than 5,000 women aged between 34 and 77 who were free of the disease before the study began and who were taking higher doses of paracetamol (acetaminophen), non-selective non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin.

Amongst 1,903 older women aged between 51 and 77 from the first Nurses Health Study cohort, the relative risk of developing hypertension with paracetamol use was 1.93 (1.30-2.88) and with ibuprofen was 1.78 (1.21 to 2.61). Amongst younger women aged 34 to 53 from the second Nurses Health Study cohort, the relative risk of developing hypertension among paracetamol-users was 1.99 (1.39-2.85). For ibuprofen use the relative risk was 1.60 (1.10-2.32).

An earlier analysis in 2002 showed a 20% increased relative risk of hypertension among women who used paracetamol for at least 22 days per month but did not stratify risk by dose. The same analysis showed a 35% increase in relative risk for ibuprofen.

The current study drew comments from specialists attending the 11th World Pain Congress in Sydney. Dr Gary Williams, a rheumatologist from Scripps Clinic, La Jolla, California said the finding added to the problems of prescribers who were under pressure to switch arthritic patients from remaining coxibs to safer alternatives to avoid cardiovascular risks. Paracetamol is regarded as the drug of choice for patients with osteoarthritis but hypertension is a key factor behind the increased relative risk of myocardial infarction associated with drug treatments for arthritis, he explained.

“There are no data to support NSAIDs or paracetamol as being any safer than celecoxib [Pfizer’s Celebrex]. In fact, the totality of data including the FDA designed and financed study of 1.4 million patients using analgesic drugs, suggest celecoxib is probably the one in the lowest realm of risk.” Paracetamol had also been shown to cause effects on the gastro-intestinal tract with doses above 126mg day, he added.

Zurich-based cardiologist Dr Frank Ruschitzka said he was not surprised by the paracetamol findings, which he believed were mediated via the kidney. “A precursor of paracetamol was phenacetin and this was the single, most common cause of renal problems. The drug was modified to become less nephrotoxic and became paracetamol.” Analgesic drugs for arthritis had not been studied properly for cardiovascular safety and renal effects, he said.

Dr Williams said: “Large prospective randomised double blind trials comparing cardiovascular outcomes for coxibs and alternative treatments are needed so that doctors can feel comfortable with the way drugs are ranked for safety.”

The FDA’s current position as of April 2005 is that non-selective NSAIDs and coxibs should carry the same warning regarding the potential for adverse events. The European regulatory authority has changed the indications for coxibs to preclude their use in patients with established cardiovascular disease and for caution to be exercised when prescribing for patients with cardiovascular risk factors. It is expected to conclude a review of NSAIDs in September.