Risk of myocardial infarction and re-operation is greater than for drug-coated stents
If narrowed or blocked coronary vessels have to be widened or opened, a vascular support (stent) is usually inserted. Drug-coated stents are preferred for patients at high risk of renewed narrowing of vessels (restenosis). However, the use of antibody-coated stents has been increasing in recent years. Current studies provide indications that these new antibody-coated stents more frequently lead to myocardial infarction and make re-operation necessary. This is the conclusion reached in the rapid report of the German Institute for Quality and Efficiency in Health Care (IQWiG), as published on 12 October 2012.
Focus on patients with a high risk of restenosis
The Federal Joint Committee (G-BA) had commissioned IQWiG to investigate the advantages and disadvantages of antibody-coated stents in comparison to alternative measures, focussing on patients with coronary heart disease (CHD) at high risk of restenosis. This depends on factors including the duration and degree of the narrowing as well as its precise localization. The curvature of the affected vessels can also play a role.
Even stented vessels may become blocked again
Narrowed coronary vessels are generally expanded by surgery and stabilized with stents (tubes of wire mesh). But even vessels supported by stents can become blocked again, if there is excessive tissue growth. Re-operation is then necessary (revascularization). Moreover, stents are foreign bodies. If they are not fully covered with a smooth cell layer (epithelium), platelets are more likely to stick to them and blood clots (thromboses) are more likely to form on them. It is attempted to counteract these two main risks (thrombosis formation and tissue proliferation) by specifically coating the stent and by treating the patient with anticoagulants.
Risk of thrombosis increases
The first generation of stents consisted of pure metal (bare-metal stents, BMS) and are now rarely used for patients at high risk of restenosis. The second generation of stents were coated and released small quantities of drugs (drug-eluting stents, DES). These drugs are meant to inhibit cell growth and thus avoid restenosis and the need for revascularization.
On the other hand, this coating delays incorporation of the stent, thus increasing the risk of thrombosis. Therefore patients with a DES must generally take antithrombotic drugs for at least 12 months after the operation. The active substances acetylsalicylic acid (ASS) and clopidogrel - so called platelet inhibitors - are most frequently used.
Antibody-stents are intended to reduce the use of anticoagulants
The third generation of stents act by using specific antibodies to stimulate cells growing into the vascular wall to form epithelium. This is supposed to accelerate the incorporation of the wire network and reduce the risk of thrombosis. The manufacturer claims that this greatly shortens the period for which antithrombotic drugs must be taken, thus helping to avoid the side effect of an increased tendency to bleed and also helping to reduce costs.
Two of three studies susceptible to bias
Three randomized controlled trials (RCTs) were available to IQWiG. Two studies compared antibody-stents with DES; one study compared antibody-stents with BMS. One DES study and one BMS study had only a few participants and were prematurely discontinued. These discontinuations were not planned, i.e. the criteria for stopping the studies had not been specified before the start of the studies. Moreover, it was unclear in one of the studies whether the randomized allocation to the two treatment groups was adequately concealed. These studies were thus highly susceptible to bias and the results can only be used to a limited extent.
In accordance with the mechanism of action of antibody-stents, the patients in all three studies were only given clopidogrel for one month. In contrast, the patients in the control groups were given clopidogrel for either 3 months (DES) or for six months (BMS).
The comparison with DES is mainly based on a single study
The comparative benefit assessment of DES- and antibody-stents is mainly based on a single study (TRIAS-HR). This was comparatively large - with 600 patients - and the risk of bias was low. Of the 304 patients who had been given an antibody-stent, 13 (4.3%) suffered a myocardial infarction, in comparison with 5 of 318 patients (1.6%) in the control group with DES.
The results for antibody-stents were also less favourable with respect to revascularization: re-operation was necessary for 71 of 297 (23.9%) patients in the antibody-stent group, in comparison with 51 of 315 patients (16.2%) in the DES group. As this conclusion was only based on a single study, IQWiG considers that there is no proof, but only an indication, of lesser benefit. This applies both to the outcome of myocardial infarction and to the outcome of revascularization.