In patients with coronary heart disease requiring a stent implantation, the benefit of treatment with antibody-coated drug-eluting stents (ABC-DES) versus drug-eluting stents without antibody coating (DES) is still unclear. This is the result of a final report published on 20 November 2015, which the German Institute for Quality and Efficiency in Health Care prepared on behalf of the Federal Joint Committee (G-BA).
The only two studies available comparing ABC-DES with DES were too small to be able to infer reliable conclusions on patient-relevant outcomes, and the data are insufficient for most outcomes. No comparative studies with treatment options other than DES were identified, nor did the commenting procedure after the preliminary report yield any information gain. There is thus no hint of a benefit of ABC-DES versus DES.
ABC-DES are supposed to render blood thinners superfluous
ABC-DES are coated with immunosuppressive drugs on their outer side (the side towards the wall of the blood vessel). On their inner side (the side towards the lumen of the blood vessel), they are coated with antibodies to promote adherence of endothelial cells to the mesh of the stent.This is supposed to shorten the duration of treatment with blood thinners, without increasing the risk of re-narrowing of the vessel (restenosis) or formation of blood clots (thrombosis).
Treatment with blood thinners over several months is the standard after DES implementation, but can be problematical in some patient groups, for example, in those who are scheduled to undergo major surgery. In addition, DES implantation is often inadvisable in patients who already have to take blood thinners permanently due to a different disease, as then 3 blood thinners would usually be required in parallel. It would thus be helpful if stents with the efficacy of DES, but without the need for long-term blood thinners, were available.
Available studies do not show a relevant difference
The results in the only two studies available (REMEDEE and REMEDEE OCT) do not show relevant differences between ABC-DES (tradename Combo) and the stents coated with drugs alone (DES) produced by different manufacturers.
In the REMEDEE study it was to be shown that ABC-DES (test group: 124 patients) were non-inferior to DES (control group: 59 patients). In the REMEDEE OCT study the superiority of ABC-DES over DES (29 patients vs. 31 patients) was to be shown. Neither of the two studies was designed to assess the patient-relevant benefit; tissue integration of ABC-DES versus DES was assessed instead.
Both studies provided data on the patient-relevant outcomes of mortality, myocardial infarction, cardiac bypass surgery, overall rate of serious adverse events, vascular complications, cerebrovascular events, and bleeding events. However, the data are insufficient for several outcomes and in many respects uncertain. Due to the different drug coatings of the various DES types, it is also unclear what impact antibody coating actually had on the study results.
Benefit or harm of ABC-DES versus DES is unclear
In patients requiring a stent implantation due to coronary heart disease, the benefit or harm of the new generation of stents (ABC-DES) versus DES is thus still unclear.
In patients with a high risk of restenosis, a previous assessment by IQWiG in October 2012 (rapid report N12-01) showed indications of a lesser benefit of ABC stents solely coated with antibodies versus DES. In March 2013, the G-BA subsequently excluded implantations with ABC stents from reimbursement by statutory health insurance in those patients who were also eligible for DES implantation.
For patients with coronary heart disease in whom a stent is indicated, it remains open whether the currently ongoing HARMONEE and RECOVERY studies can answer the question with regard to the benefit and harm of ABC-DES versus DES. None of the ongoing studies is designed to assess the patient-relevant benefit.
DES dominate stent implantations in patients with coronary heart disease
In Germany in 2013, a DES was used in nearly 80% of patients in whom a stent implantation was indicated; bare metal stents (BMS) were used in the remaining 20%. BMS are primarily suitable if treatment with blood thinners is problematical due to concomitant diseases of the patient. In contrast, ABC-DES have so far not played a relevant role in clinical practice and, for example, are given little attention in German or international guidelines.
One reason for the increasing number of stent implantations is, among others, the continuous further development of stents. Stefan Sauerland, Head of IQWiG's Department of Non-Drug Interventions, describes the current situation in health care: "It has been shown that modern DES are also being increasingly used in patients who were previously treated exclusively with BMS. The characteristics of second-generation DES are also gradually changing recommendations on the duration of necessary dual anti-platelet therapy following implantation: The shortened treatment period for blood thinners increases the number of patients eligible for DES implantation, thus reducing the need for ABC-DES."
Process of report production
IQWiG published the preliminary results in the form of the preliminary report in July 2015 and interested parties were invited to submit comments. At the end of the commenting procedure, the preliminary report was revised and sent as a final report to the commissioning agency in September 2015. The written comments submitted were published in a separate document together with the final report. The report was produced in collaboration with external experts.
An overview of the background, methods and further results of the final report is provided in the following German-language executive summary. An English-language executive summary will be available soon. If you would like to be informed when this document is available, please send an e-mail to » email@example.com.