The PROVE IT* study, published last year, is claimed to confirm an advantage of 80 mg daily atorvastatin (SORTIS) over pravastatin (PRAVASIN etc.) in standard dose (40 mg) in patients with acute coronary syndrome. Started immediately after the acute event, the risk of dying or suffering from vascular complications within two years is said to fall from 26.3% to 22.4%. It is still uncertain whether these effects are attributable to the high dose or to particular properties of atorvastatin. It also remains uncertain whether treatment lasting for two years is actually necessary. According to subgroup analyses, only younger patients without ST-elevation infarction and without previous statin treatment benefit (1). On the basis of the PROVE IT study, we felt that a two-year high-dose treatment with atorvastatin appeared to be justifiable only for these patients (a-t 2004; 35: 41-2).

Now the Institut für Qualitaet und Wirtschaftlichkeit im Gesundheitswesen [Institute of Quality and Economy in Healthcare] (IQWiG) has expressed doubts about the validity of the PROVE-IT data when comparatively assessing the benefit of all statins (2). The Institute discovered considerable inconsistencies in the details of the number of patients lost to follow-up. In the text of the PROVE IT study it is stated that only 8 (0.2%) of the 4,162 patients were lost in the planned minimum follow-up period of 18 months, which apparently was effectively performed. In contrast, according to the data in a graph showing the results, about 267 participants are already missing after 12 months. This figure greatly exceeds the difference given as the advantage in the primary endpoint between atorvastatin and pravastatin of an absolute 3.9% or about 80 events. If it is assumed that at least 267 patients were actually lost to follow up, the result does not withstand a so-called worst-case analysis. The statement that only 8 patients were lost is also in conflict with a later publication (3) by the authors, which mentions 63 patients who withdrew their consent for follow-up (2).

There has been no statement on the part of the PROVE IT authors so far. Until a satisfactory explanation for the considerable inconsistencies is found, we regard the results of the PROVE-IT study, hitherto assessed positively by our arznei-telegramm staff - though with reservations - as no longer scientifically valid. With the current state of knowledge, we therefore see no longer adequate justification for early statin therapy in the acute coronary syndrome.

With the PROVE-IT study, the supporting pillar of the argument of the manufacturer of atorvastatin, Pfizer, topples, which claims a special status for its statin in the fight against reference pricing for all statines effective since this year (a-t 2004; 35: 135-6). As the benefit assessment of the IQWiG on the basis of randomised controlled double-blind studies with clinical endpoints shows, better proof of benefit is available for pravastatin (PRAVASIN etc.) and simvastatin (DENAN etc.) in stable coronary heart disease and for simvastatin in diabetes (2).

(R = randomised study)

1

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

2

Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen [Institute of Quality and Economy in Healthcare] (IQWiG): Assessment of the benefits of the statins with particular consideration of atorvastatin, 15. Aug. 2005; available at http://www.iqwig.de

3

CANNON, C.P. et al.: N. Engl. J. Med. 2004; 351: 714-7

4

SCHÜSSEL, K.: Pharm. Ztg. 2005; 150: 3410-3

PROVE IT = Pravastatin or Atorvastatin Evaluation and Infection Therapy