"Savings will be performed from January. On account of the health of millions of cardiovascular patients. From 1st January 1.5 million patients in the statutory sickness funds will no longer be fully reimbursed ... SORTIS lowers cholesterol levels the most, reduces the risk fastest and is also well tolerated even at the highest dose" (1). With such headlines, Pfizer stokes fears in the consumer. The competent Regional administrative Council in Karlsruhe has now filed a court injunction against the company, as the advertisements in the daily newspapers contravene the medicine advertising act. Prescription medicines must not be advertised in the lay press, particularly not with formulations that can produce anxiety in the consumer (2). However, Pfizer continues to contravene the medicine advertising act with the most recent advertisement series "Can publicly insured patients really do without SORTIS?" (3).

With its campaign, the company is reacting to the decision of the Joint Federal Committee to include atorvastatin together with the other HMG-CoA inhibitors available on the market, simvastatin (ZOCOR etc.), pravastatin (PRAVASIN etc.), fluvastatin (CRANOC etc.) and lovastatin (MEVINACOR etc.) in a common reference price group ("jumbo group") and thus reduce the cost of these high-priced medicines. Pfizer does not want to reduce the costs for atorvastatin (annual sales worldwide 8 thousand million €) to the fixed amount, and - especially - does not want to jeopardise the internationally established price level for SORTIS through unilateral price reductions in Germany. The consequence for the patients are substantial surplus charges, which will be liable from 2005 (e.g. 48.51 € for 100 SORTIS 40 mg tablets). The suppliers of the simvastatin and pravastatin originals must also reduce the prices in order to avoid patient payment contributions. For atorvastatin there are still no cheap generics (patent expiring not before 2011).

Pfizer obtains willing back-up support from the "Ärzte Zeitung", in which there is a polemic against the decision of the Joint Federal Committee (G-BA) and a statement of the Institute for Quality and Economy in Healthcare (IQWiG) (4). However, extolling atorvastatin as the "best cholesterol-lowering agent" proves to be wishful thinking by the manufacturer when the data are analyzed carefully:

	For the most important indication, secoundary prevention of cardiovascular events in patients with known, but stable chronic atherosclerotic disease, there are only two methologically dubious studies (ALLIANCE and GREACE)* (5,6), in which atorvastatin used by a specialised center is compared to a "usual" treatment in general practice. Valid statements on the benefit of atorvastatin cannot be derived from such studies, since the treatment differs markedly in the compared groups, apart from the investigated intervention. The findings of clinical trials in secondary prevention are still the best for 20 mg to 40 mg simvastatin (4-S, HPS) (7,8) and 40 mg pravastatin (CARE and LIPID) (9,10). Both statins reduce the rate of major coronary events in these patients and lower mortality (a-t 2004; 35: 56-60).
	For primary prevention, the ASCOT-LLA (11) is the only randomised controlled study with atorvastatin in patients without cardiovascular disease (primary prevention). Patients with hypertension and at least three other risk factors took part. The incidence of major coronary events was reduced slightly, but not mortality. However, according to large studies similar results were obtained with pravastatin (WOSCOP) (12) and lovastatin (AFCAPS/TexCAPS) (13) (a-t 2004; 35: 56-60).
	In diabetics without known cardiovascular disease but with high coronary risk, similar data are available. A benefit is confirmed for atorvastatin in the CARD study (14) just as for simvastatin in HPS (15) in these patients. In ASCOT-LLA the subgroup of diabetics, accounting for 25% of the patients, does not profit from atorvastatin. Because of the overall more qualified data, we regard simvastatin as the agent of choice in this indication, too (a-t 2004; 35: 93-4).
	There is very limited experience for all statins in the treatment of homozygous familial hypercholesterolaemia or children with severe dyslipidaemias. In the SORTIS summary of product characteristics (SPC) (16) there is only a reference to an apparently unpublished study of 64 patients suffering from homozygous familial hypercholesterolaemia. The experience of therapy with atorvastatin in children is limited to a small number aged between 4 and 17 years.
	In our view, the only difference to other statins is found in the temporally limited therapy of the acute coronary syndrome with 80 mg atorvastatin daily. While early high-dosage use of simvastatin compared to later low-dosage use conferred no benefit (a-t 2004; 35: 94), there are positive results in this indication for high-dose atorvastatin in MIRACL (17) (against placebo) and PROVE-IT (18) (against 40 mg pravastatin). However, in PROVE-IT only patients under 65 years without myocardial information with ST-segment elevation showed a benefit. But there was no reduction in mortality in either of the two studies. The PROVE-IT study, which is claimed to confirm the superiority of atorvastatin, also leaves the question unanswered of whether the high dosage or specific substance characteristics are responsible for the claimed additional benefit (a-t 2004; 35: 41-2).

That atorvastatin produces less severe side effects cannot be stated for usual dosages: the evaluation of statin-induced myopathy from the American FDA's ADR reporting system too for the time period 1990 to 2002 indicates a similar incidence of rhabdomyolsis for all statins on the market taking into account the prescription figures (19). A recent analysis of the data from eleven regional American healthcare providers shows a similar incidence for atorvastatin, simvastatin and pravastatin (20).

	A superior efficacy of atorvastatin (SORTIS) compared to other statins has not been confirmed either for primary or for secondary prevention of cardiovascular diseases. For the majority of patients, confirmation of an advantage of atorvastatin is therefore lacking.
	In the most important indication for a statin, the secondary prophylaxis of chronic atherosclerotic diseases, equivalence with the established statins simvastatin (ZOCOR etc.) and pravastatin (PRAVASIN etc.) is not even proven.
	We regard the advertising campaign of the manufacturer as panicmongering and deliberate misleading of the public, with which Pfizer is attempting to safeguard unrestricted sales of the product (515 million Euro/year through public pharmacies).

(R = randomised study)

1

Pfizer GmbH: advertisement for SORTIS, Süddt. Ztg. of 10th Nov. 2004

2

Karlsruhe Regional Council: press release of 26th Nov. 2004

3

Pfizer GmbH: advertisement for SORTIS, Süddt. Ztg. of 26th Nov. 2004

4

Ärzte Ztg. of 1st Dec. 2004

5

KOREN, M.J., HUNNINGHAKE, D.B.: J. Am. Coll. Cardiol. 2004; 44: 1772-9

6

ATHYROS, V.G. et al.: Curr. Med. Res. Opin. 2002; 18: 220-8

7

Scandinavian Simvastatin Survival Study Group: Lancet 1994; 344: 1383-9

8

Heart Protection Study Collaborative Group: Lancet 2002; 360: 7-22

9

SACKS, F.M. et al.: N. Engl. J. Med. 1996; 335: 1001-9

10

The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group: N. Engl. J. Med. 1998; 339: 1349-57

11

SEVER, P.S. et al.: Lancet 2003; 361: 1149-58

12

SHEPHERD, J. et al.: N. Engl. J. Med. 1995; 333: 1301-7

13

DOWNS, J.R. et al.: JAMA 1998; 279: 1615-22

14

COLHOUN, H.M. et al.: Lancet 2004; 364: 685-96

15

COLLINS, R. et al.: Lancet 2003; 361: 2005-16

16

Pfizer: Fachinformation SORTIS, Stand Jan. 2003

17

SCHWARTZ, G.G. et al.: JAMA 2001; 285: 1711-8

18

CANNON, C.P. et al.: N. Engl. J. Med. 2004; 350: 1495-504

19

THOMPSON, P.D. et al.: JAMA 2003; 289: 1681-90

20

GRAHAM, D.J. et al.: JAMA 2004; 292: 2585-90

4-S = Scandinavian Simvastatin Survival Study;
AFCAPS/TexCAPS = Air Force/Texas Coronary Atherosclerosis Prevention Study;
ALLIANCE = Aggressive Lipid-Lowering Initiation Abates New Cardiac Events;
ASCOT-LLA = Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm;
CARDS = Collaborative Atorvastatin Diabetes Study;
CARE = Cholesterol And Recurrent Events Trial;
GREACE = Greek Atorvastatin and Coronary-heart-disease Evaluation;
HPS = Heart Protection Study;
LIPID = Long-Term Intervention with Pravastatin in Ischaemic Disease Study;
MIRACL = Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering;
PROVE-IT = Pravastatin or Atorvastatin Evaluation and Infection Therapy;
WOSCOP = West of Scotland Coronary Prevention Study