There are several areas of therapeutics where current practice differs between the United States and Europe. In the case of nesiritide, the use of this drug is undoubtedly controversial. This recombinant human brain natriuretic peptide is given to tens of thousands of patients in the United States every week at a cost of about $500 for each dose, and many physicians there are extremely enthusiastic about this new treatment for acute decompensated heart failure (ADHF).
Aggressive marketing by the manufacturer, Scios Inc, has been suggested as one reason for its increasing use1 while many cardiologists in Europe are far less enthusiastic and have questioned whether nesiritide offers any improvement over current optimal management. Also the European Agency for the Evaluation of Medicinal Products has still not approved nesiritide and awaits the results of a trial involving 1900 patients before it will even consider doing so. In the UK, the assessment of nesiritide by the National Institute for Clinical Excellence is going at a snail’s pace and will not make any recommendations until August 2007.
One recent meta-analysis published in March this year has suggested that nesiritide significantly increases the risk of worsening renal function in patients with ADHF,2 and another published a month later concluded that nesiritide may be associated with an increased risk of death after treatment for ADHF.3
Scios Inc have stated in a letter to physicians and patient advocates dated 6 May 2005 that they remain confident in the safety profile of nesiritide and the benefits it offers to patients with acute decompensated heart failure. Differences of opinion on either side of the Atlantic appear set to continue.
In the case of rosuvastatin, Europe and the US again seem at variance. Concerns were expressed in correspondence in a UK journal4 that rosuvastatin has an as yet unproven safety record, but family doctors and specialists are keen to prescribe it, even to individuals with no previous experience with lipid-lowering drugs, and to some who have predisposing risk factors for a potentially lethal side-effect. This was followed in June 2005 by new research that suggested that this drug, which has not been used in end-point trials, caused more kidney and muscle problems than rival medications although the rate of these complications was low.5
The US Food and Drug Administration has contended that rosuvastatin’s risks are no greater than its competitors and rejected consumer efforts to remove the drug from sale, but did order a label warning that serious muscle problems and kidney damage could occur, especially among Asians.
Manufacturer AstraZeneca strongly disagreed with the conclusions of the Circulation study and said the higher reports of side-effects may have been the result of heightened awareness of the problems following the withdrawal of cerivastatin in 2001. But in the UK, the Medicines and Healthcare Product Regulatory Agency issued advice as long ago as May 2004 that all patients start on 10 mg daily, and that the40- dose is contraindicated in patients with predisposing risk factors for muscle toxicity.
Future issues of Circulation: European perspectives in cardiology will follow forthcoming developments and look at other variations in practice.
Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation. 2005; 111 (12): 1487–91.
Florentinus SR, Heerdink ER, Klungel OH, de Boer A. Should rosuvastatin be withdrawn from the market?. Lancet. 2004; 364 (9445): 1577.
Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH. The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation. 2005; 111 (23): 3051–7.