In order to better prevent blood clots, the drugs Clopidogrel ( Plavix ) or Prasugrel ( Efient, Effient ) can be prescribed to patients with coronary heart disease, in addition to Acetylsalicylic acid ( ASA; Aspirin ).
The German Institute for Quality and Efficiency in Health Care ( IQWiG ) has investigated whether, in patients whose vessels were dilated by a percutaneous coronary intervention ( PCI ), the combination of Prasugrel plus Acetylsalicylic acid has a higher patient-relevant benefit than ASA alone, or than combination therapy with Clopidogrel plus Acetylsalicylic acid. 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.

Like Clopidogrel, prasugrel is an anti-platelet drug that is used in a similar way to Acetylsalicylic acid. It inhibits parts of the blood-clotting system, leading to a reduction in platelet clotting and of the subsequent formation of blood clots. Prasugrel is thus supposed to reduce the risk of myocardial infarctions and strokes. However, the risk of bleeding may increase.
As the manner in which Prasugrel and Acetylsalicylic acid act on blood clotting differs, it is assumed that the two 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.

Prasugrel is approved in Germany solely in combination with Acetylsalicylic acid 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 Acetylsalicylic acid combination therapy versus ASA monotherapy, but not versus Clopidogrel plus Acetylsalicylic acid combination therapy.

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 Acetylsalicylic acid 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 Acetylsalicylic acid 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.

In patients with a minor heart attack or unstable angina, i.e. patients with a non-ST-segment-elevation myocardial infarction ( UA / NSTEMI ), IQWiG found indications of a potential advantage of Prasugrel plus ASA versus Clopidogrel plus ASA. In the TRITON study, patients taking Prasugrel suffered fewer non-fatal heart attacks or strokes, or required fewer interventions with a balloon catheter for dilatation of the coronary vessels.
IQWiG does not interpret these results as proof, but only as an indication of an advantage of Prasugrel, as the study participants only received the medications some time after the occurrence of heart attack symptoms. As Prasugrel generally has a more rapid onset of effect, Clopidogrel was presumably systematically disadvantaged by the study design.
Moreover, regarding the prevention of a stroke, the indication of an additional benefit of Prasugrel only applies to certain patients, as such indications were only found in the studies in patients without a known history of vascular disease.

At the same time, IQWiG also found indications of greater harm, as major bleeding events occurred more often with Prasugrel plus Acetylsalicylic acid than with Clopidogrel plus ASA. This included, for example, bleeding events that required a blood transfusion.
Neoplasia ( benign and malignant tumours ) were also diagnosed more often in patients treated with Prasugrel. However, due to the more common occurrence of bleeding, patients treated with Prasugrel were also closely examined more often. It is therefore possible that additional tumours not detected in patients taking Clopidogrel were detected by chance in such examinations. As the results of the TRITON study cannot be interpreted with certainty, IQWiG only sees a hint ( i.e. no indication or proof ) of greater harm.

Source: IQWiG, 2011

XagenaMedicine2011


Link: Xapedia - Medical Encyclopedia