Compared with clopidogrel, non-fatal heart attacks occur less often in certain patients, but major bleeding events are more common
In order to better prevent blood clots, the drugs clopidogrel or prasugrel can be prescribed to patients with acute ischaemia of the heart muscle, in addition to acetylsalicylic acid (ASA). The German Institute for Quality and Efficiency in Health Care (IQWiG) has now investigated whether, in patients whose vessels were dilated by a percutaneous coronary intervention (PCI), the combination of prasugrel plus ASA has a higher patient-relevant benefit than ASA alone, or than combination therapy with clopidogrel plus ASA. The findings of the assessment provide indications that prasugrel decreases the risk of further non-fatal heart attacks better than clopidogrel in some patients, but that major bleeding events occur more often. This is the result of a final report presented by IQWiG on 5 September 2011.
ASA and prasugrel should complement each other in their effect
Prasugrel has been available on the German market since 2009 under the trade name "Efient-" and in some patients can be used as an alternative to the drug clopidogrel, which was already assessed by IQWiG in 2009.
Like clopidogrel, prasugrel is an anti-platelet drug ("platelet aggregation inhibitor") that is used in a similar way to ASA. It inhibits parts of the blood-clotting system, leading to a reduction in platelet clotting (aggregation) and of the subsequent formation of blood clots (thrombi). Prasugrel is thus supposed to reduce the risk of heart attacks and strokes, for example. However, the risk of bleeding may increase. As the manner in which prasugrel and ASA act on blood clotting differs, it is assumed that the 2 drugs complement each other and that the overall inhibitory effect on the formation of blood clots increases. Prasugrel differs mainly from clopidogrel through its faster onset of action, and is intended to be used if a rapid treatment effect is required.
Different approval status for clopidogrel and prasugrel
Prasugrel is approved in Germany solely in combination with ASA for patients with acute coronary syndrome (ACS), i.e. with acute stenosis of the coronary vessels, who are to undergo surgery in the form of a PCI to dilate their vessels. These patients have either unstable angina pectoris or have suffered an acute heart attack.
In contrast to prasugrel, clopidogrel is not approved in patients who experienced a "severe" heart attack (i.e. an "ST-segment-elevation myocardial infarction", STEMI) and therefore undergo a PCI. However, in practice, clopidogrel is still also commonly used in these patients, but it has not yet been sufficiently investigated in studies whether they benefit from this. Following the requirements of the contracting agency, the Federal Joint Committee (G-BA), the benefit assessment of prasugrel was to be conducted within the approval status valid in Germany. Accordingly, in patients with STEMI, IQWiG only compared prasugrel plus ASA combination therapy versus ASA monotherapy, but not versus clopidogrel plus ASA combination therapy.
Two studies included in the assessment
IQWiG included 2 studies in the assessment: in one long-term study (TRITON), patients were followed between 6 and 15 months, and in one short-term study (JUMBO) up to 35 days. TRITON and JUMBO were randomized controlled trials, and both compared the combination therapies prasugrel plus ASA versus clopidogrel plus ASA.
In both studies, large groups of participants were treated differently than envisaged in the German approval conditions for prasugrel and clopidogrel. IQWiG could therefore use the results only for the subgroups of participants receiving approval-compliant treatment. In this context, IQWiG's conclusions are primarily based on the TRITON study, as, with several thousand patients, considerably more patients received approval-compliant treatment than in the JUMBO study (less than 200 patients).
Studies comparing prasugrel plus ASA with ASA monotherapy were not available, which is why the final report cannot draw any conclusions on advantages and disadvantages of prasugrel in patients with STEMI.
No proof, but indication of a benefit