Clopidogrel: Not beneficial for all patients

No evidence currently exists that long-term antiplatelet monotherapy with clopidogrel versus acetylsalicylic acid (ASA) has an overall additional benefit in preventing complications in patients with vascular disease (secondary prevention). In contrast, an additional benefit of long-term clopidogrel therapy has been demonstrated (compared with ASA) in patients with symptomatic peripheral arterial disease. The current studies available do not provide evidence that clopidogrel is superior to ASA in increasing quality of life or treatment satisfaction. This is the result of the final report published on 25 August 2006 by the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG).

The Federal Joint Committee ( Gemeinsamer Bundesausschuss, G-BA) commissioned IQWiG to evaluate the benefits and harms of clopidogrel in patients with heart and/or other vascular disease. The Institute was specifically asked to evaluate the benefits and harms of clopidogrel and ASA as antiplatelet monotherapy for secondary prevention in patients with ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD), or symptomatic peripheral arterial disease (PAD).

In addition, it was to be assessed whether a switch of treatment from ASA to clopidogrel had a beneficial effect on patient-relevant therapy goals in patients who had previously suffered an adverse event during ASA therapy (thromboembolic event or severe bleeding).

Benefit only shown in patients with symptomatic peripheral arterial disease

Compared with ASA, long-term antiplatelet monotherapy with clopidogrel in patients with symptomatic PAD has an additional benefit. The literature analysis showed that the risk for vascular/thromboembolic events, such as a myocardial infarction or stroke, was significantly reduced in this subgroup of patients. However, a reduction in all-cause mortality was not shown. No evidence was available to demonstrate a superiority of clopidogrel in patients with asymptomatic PAD. It was also unclear, whether in patients with IHD or ICVD (without co-existing PAD), clopidogrel has beneficial or even detrimental effects compared with ASA. In this context, IQWiG criticizes that the essential results of a study already completed including patients with IHD have not yet been fully published, thereby possibly condoning the suboptimal care of patients.

No evidence exists that in patient groups with an increased risk of thromboembolic events (e.g., patients with hypercholesterolaemia, diabetes mellitus, or manifestations of atherosclerosis in more than 1 vascular territory), clopidogrel has a particularly beneficial effect compared with ASA. According to the evidence available, patients who experienced a bleeding complication during low-dose ASA therapy do not profit from a switch to clopidogrel. On the contrary, there is some indication that a higher benefit for patients is achieved with combination therapy including low-dose ASA plus a proton pump inhibitor than with a switch of therapy.

No valid data available on quality of life and pain

In general, none of the studies included aimed to evaluate the beneficial or detrimental effects of the investigated therapy options on patients' quality of life. For example, none of the studies contained information on whether clopidogrel is more effective than ASA in reducing disease-related symptoms such as pain (when walking or resting) or angina pectoris symptoms. Nor was information available that indicated that clopidogrel increases patients' physical capacity or the ability to perform daily activities.

Contact: info@iqwig.de