IMPORTANT: This press release accompanies both a presentation and an ESC press conference given at the ESC Congress 2003. Written by the investigator himself/herself, this press release does not necessarily reflect the opinion of the European Society of Cardiology
ESC Congress 2003: Hot Line II – Acute coronary syndromes / percutaneous coronary intervention
Efficacy and safety of 6 month treatment with the oral direct thrombin inhibitor, ximelagatran, in combination with acetylsalicylic acid, in patients with a recent myocardial infarction: the ESTEEM* study
Tuesday 1 September 2003: The first study of a new oral anticoagulant, ximelagatran in patients after a heart attack, ESTEEM, shows that compared with placebo, ximelagatran reduces the risk of death, recurrent heart attack or attacks of severe chest pain from 16.3 % to 12.7 % during six months treatment (p=0.036). This corresponds to a relative risk reduction of 24% – meaning that patients treated with ximelagatran are 24% less likely than those treated with placebo to suffer a recurrent heart attack, severe chest pain or death. This improvement was seen in comparison to placebo when given on top of the current standard treatment, aspirin. There was an even more pronounced reduction in the combination of death, heart attack and stroke from 11.1 % to 7.4 % corresponding to a relative risk reduction of 34 % (95% Confidence Interval: 48% – 90%). There was no difference in efficacy between different doses of ximelagatran
"The results of this study are very exciting as they show the first proof of the efficacy of oral direct thrombin inhibition in this new indication, and demonstrate that this new concept holds great promise for better protection against heart attack and stroke in patients at risk of further cardiovascular events", comments Professor Lars Wallentin, Professor of Cardiology at Uppsala University Hospital, Sweden, and Lead Investigator for the ESTEEM study.
ESTEEM is a randomised, placebo-controlled, double blind dose-guiding study that included 1883 patients in 191 hospitals in 18 countries throughout 2001-2002. Within 14 days of a heart attack patients were randomised to six months treatment with tablets twice daily of either 24, 36, 48 or 60 mg of ximelagatran or placebo. This treatment was added to the current standard treatment with aspirin and other drugs known to protect against new heart attacks.
Major bleeding events were uncommon and occurred in only 1.8 % of patients during treatment with ximelagatran and 0.9 % during treatment with placebo, although this was not statistically significant. As with all medications that target blood clotting, there was a slightly raised risk of minor bleeding, which was higher at the higher dose levels of ximelagatran.
As seen in other studies, ximelagatran use was associated with a risk of liver enzyme elevation in biochemical tests of liver function. These typically were transient, occurred within 2-4 months but decreased towards normal over 1-3 months either with continued or discontinued treatment. These effects were least at the lowest dose of ximelagatran 24 mg twice daily, where a transient elevation of liver tests was seen in 6.5 % of patients.
The investigators conclude that the lowest dose level of ximelagatran achieved maximum efficacy with an acceptable safety profile for long-term treatment after a heart attack in this study.???Confirmatory results on efficacy, safety and the clinical potential of this treatment in this indication are now required in larger phase III studies.
Heart attack and stroke are the most common cause of death and disability in the developed countries. The condition is caused by the formation of a blood clot at an atherosclerotic lesion in an artery to the heart or brain, which blocks the flow of oxygenated blood to the tissue.
Ximelagatran is the first in a new class of oral anticoagulant treatment, oral direct thrombin inhibitors, under investigation by AstraZeneca for prevention and treatment of thrombotic diseases.???The safety and efficacy of 24mg and 36 mg Exanta twice daily for prevention and treatment of venous thromboembolism and for the prevention of strokes in patients with atrial fibrillation have been documented in a large research and development program which has included 30,000 patients to date.
Department of Cardiology, Uppsala Clinical Research Center, Uppsala
European Society of Cardiology (ESC). September 2003.