ASSENT-3+ (ASsessment of the Safety and Efficacy of New Thrombolytic regimens) confirms the reduction in ischaemic events seen in the ASSENT-3 study for patients suffering from a heart attack (acute ST elevation myocardial infarction, STEMI). The trial results were presented at the American Heart Association's Scientific Sessions 2002.
The ASSENT-3+ study, a hypothesis-generating trial, involved 1,639 heart attack patients from Canada and Europe, treated in the ambulance pre-hospital setting with a combination of the thrombolytic (clot-buster) Metalyse /TNKase (tenecteplase, TNK) with Clexane/Lovenox (enoxaparin) or unfractionated heparin (UFH). “Pre-hospital thrombolysis with Clexane/Lovenox plus TNK or UFH plus TNK reduces treatment delay by 45 minutes,” explains Lars Wallentin, MD, professor of medicine, Thoracic Centre, University Hospital of Uppsala in Sweden.
Overall, the composite efficacy endpoint1 rates were 14.2 per cent for Clexane/Lovenox plus TNK vs. 17.4 per cent for UFH plus TNK (p=0.08). The composite efficacy-safety endpoint2 rates were 18.3 per cent and 20.3 per cent respectively (p=0.3). In this complex and challenging population, there was an increase in the ICH (intracranial bleeding) rate in the Clexane/Lovenox plus TNK group as compared to UFH plus TNK. This increase was driven by the event rates in the population over the age of 75. In patients under the age of 75, ASSENT-3+ demonstrated that Clexane/Lovenox plus TNK was superior to UFH plus TNK in reducing the primary composite efficacy endpoint rates (11.2 per cent vs 15.2 per cent, p = 0.03) with comparable safety.
Clexane/Lovenox is the most widely studied and used low-molecular-weight heparin in the world. It has been used to treat an estimated 108 million patients in 96 countries since it was first introduced in 1987. Clexane/Lovenox is approved for more indications than any other low-molecular-weight heparin. Numerous clinical studies have shown that Clexane/Lovenox can safely and effectively prevent and treat potentially life-threatening venous blood clots, which can occur in many surgical and non-surgical patients, and can treat certain cardiac conditions such as unstable angina (UA) or non-Q wave myocardial infarction (NQMI). The product is known as Lovenox in the United States, Canada and France, and generally known as Clexane in the rest of the world. In 2001, sales of Clexane/Lovenox were € 1.453 billion, more than 37 percent higher than the previous year.
ASSENT 3+ was a satellite study of ASSENT-3, a 6,000 patient trial published in The Lancet in August 2001, which evaluated several combination regimens with TNK in the hospital setting. ASSENT-3 showed significant benefit in efficacy and efficacy-safety with Clexane/Lovenox as compared to UFH. A combined analysis of ASSENT-3 and ASSENT-3+ shows that Clexane/Lovenox plus TNK is superior to UFH plus TNK in the primary composite efficacy and efficacy-safety endpoints.
“ASSENT-3+ shows that pre-hospital thrombolysis with UFH plus TNK is as safe and efficacious as when given in hospital. Taking into account the reduction of ischaemic events, the ease of administration and the absence of monitoring, the combination of Clexane/Lovenox and TNK emerges as a very promising treatment. Further trials with a reduced dose regimen in patients over 75 are warranted” says Lars Wallentin.
Based on the promising results of the ASSENT-3 program and other phase II trials, Aventis is sponsoring the ExTRACT-TIMI 25 trial. ExTRACT is a 21,000 patient, multinational and indication seeking trial, investigating the efficacy and safety of Clexane/Lovenox compared to UFH in patients with heart attack (STEMI) receiving thrombolytic therapy with TNK, streptokinase, alteplase, or reteplase. Patients over the age of 75 are receiving a reduced dose regimen of Clexane/Lovenox.
According to the World Health Organization (WHO), cardiovascular diseases account for 12 million deaths in the world each year. Currently, heart attack is a leading killer of men and women in developed countries. It is projected that by 2010, heart disease will be the number-one cause of death in developing countries. This year, as many as 1.1 million people in the United States will have a coronary attack (includes heart attack and fatal coronary disease), and 4 million people throughout Europe will die of cardiovascular disease.
In the last decade, thrombolytic therapy has emerged as the standard of care for the pharmacological management of AMI. To continue to build upon the success of these products in improving treatment outcomes, cardiologists now are investigating various combinations of thrombolytics with other pharmacological agents used in the armamentarium against ischaemic heart disease.