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ePaper - CCN Ausgabe - Number 2012-4

Ausgabe 4 - Number 4 · 2012 CCNCCNCCNCCNCCNCCNCCNCCNCCNCCNCCNCCNCCCathlab &athlab &athlab & CCCardiovascularardiovascularardiovascularardiovascularardiovascularardiovascular NNNewsewsews PRODUCT NEWS Preliminary analysis of pooled data from four of the RESOLUTE clini- cal trials has recently suggested that patients who discontinued dual antiplatelet therapy after four weeks following stent implantation may not be at increased risk of stent thrombosis compared with those who maintained therapy for a longer time post-intervention. Rationale for this analysis of the pooled RESOLUTE data: It is known for many years that prolonged dual antiplatelet therapy (DAPT) is very important to prevent stent thrombosis (ST) after the implantation of drug-eluting stents (DES). However, there is some discrepancy in the guidelines regarding the duration of DAPT after implantation of DES in stable coronary patients. According to the European guidelines published in 2005 and the update published in 2010, patients should be prescribed DAPT for at least six months, while in the US-American guidelines it is at least one year. At first glance, it may not be obvious why there is such a difference between Europe and the United States. The most likely explanation is that, to date, no prospective randomized trial has ever evaluated the efficacy and safety of six months versus 12 months of DAPT. Therefore, the guideline recommendations are based on observational studies and individual experience. For first-generation DES, it is known that if one discontinues DAPT within the first six months, there is a considerably increased risk of ST, which is dangerous for the patient, because ST leads to myocardial infarction (MI) in almost every second patient, and may therefore result in death. With the newer generation DES, there is no data from randomized trials that have investigated the appropriate duration of dual antipla- telet therapy. There is, however, a considerable volume of data from clinical trials investigating the safety and efficacy of the newer DES. In the following, a post hoc analysis of data from four of the studies that were part of the RESOLUTE clinical trial program for the zotarolimus- eluting Resolute stent (Medtronic, Inc.) was performed and looked at rates of ST in relation to DAPT interruption or discontinuation. It is, of course, important to keep in mind that these data did not come from randomized clinical trials regarding the duration of DAPT. More detailed analysis: Data from the following four studies were analyzed: the randomized RESOLUTE All-Comers study (n=2,292), with a follow-up of three years; the RESOLUTE International study (n=2,349) an observatio- nal study with a follow-up of three years; the RESOLUTE US registry (n=1,402) with a follow-up of two years; and finally, the RESOLUTE Japan trial (n=100), in which patient follow-up was for two years. Of these patients, 907 had discontinued or interrupted the DAPT after at least one month following stent implantation; about two-thirds of these patients had totally discontinued and about one-third had inter- rupted and then re-started DAPT at a later point in time. In this analysis of discontinuation or interruption of DAPT from one month to one year, not a single instance of ST occurred in the follow- up period. This means that if from an analysis perspective the patient was off DAPT, having had at least four weeks of DAPT, there was no increased risk of ST in this subgroup analysis; however, if the patient discontinued before the first four weeks after stent implantation, there was a stent thrombosis rate of about 3%. This is a very striking result. This does not mean to suggest that one should recommend one month of DAPT for patients after Resolute stent implantation, but this data is reassuring that if patients have to interrupt or to discontinue, there is a very low risk of ST. These data, however, does not support early discontinuation in a high-risk population.This is a post hoc ana- lysis and, of course, there are limitations to such data. There is still a considerable amount of further evaluation needed to confirm these findings. Why might these findings be beneficial in clinical practice? DAPT increases the risk of bleeding compared with single antiplatelet therapy, so the combination of aspirin plus clopidogrel, prasugrel or ticagrelor increases bleeding. Each of these drugs increases bleeding and so the combinination of these drugs results in more bleeding and bleeding negatively affects even long-term prognosis. Ideally, mi- nimizing bleeding is achieved by cutting back the duration of DAPT. Another benefit is adherence to DAPT prescription. Sometimes the implantation of a bare metal stent (BMS) is preferred because the patient will be unable or unwilling to comply with the DAPT regimen, for example an elderly patient who may already take a large number of tablets. However, if the data show a reduced risk after only four weeks of DAPT, DES may become an option in such patients too. Indeed, data from the XIMA study (see this issue of CCN), which in- vestigated implantation of BMS versus DES in elderly (>80 years old) patients, observed that DES worked very well in those patients but there is an increased bleeding rate over time. A DES requiring only four weeks of DAPT would offer a particular advantage for elderly patients. Furthermore, as life expectancy increases and our society becomes older, the incidence of atrial fibrillation (AF), a very age-dependent disease, increases. In the future, there will be many more patients with AF, which must be managed with anticoagulation. This means treatment with vitamin K antagonists or new drugs such as rivaroxa- ban, dabigatran or apixiban, which help to prevent stroke and cere- bral bleeding. Since “triple therapy” (DAPT + anticoagulation) further increases the risk of bleeding in patients with AF, it would be better to minimize the duration of DAPT for a DES than to use a BMS. Compatibility of the data across the four RESOLUTE studies: The nice fact about the RESOLUTE program is that the protocols were harmonized before the studies started so the definitions were the same in all of the studies. This means that the data are really com- patible. All the events in the four studies included in the analysis were adjudicated by an independent data and safety monitoring commit- tee. Such activities help to ensure the quality of the dataset. Further data needed to support these findings: Randomized controlled trials represent the gold standard for evi- dence-based medicine. Therefore a randomized trial of four weeks versus six months of DAPT would be very important. At present, there are a number of ongoing randomized trials comparing different durations of dual antiplatelet therapy, such as one year of DAPT vs more than one year of DAPT or 6 months vs 12 months. However, such studies do not solve the need for studies investigating shorter treatment durations. Without results from a randomized clinical trial of four weeks versus six months DAPT, one should continue to use the European Society re- commendations of at least six months. However, if for some reason a patient has to discontinue DAPT before 6 months, these new data can help the physicians to feel more confident in doing so after implan- tation of a Resolute DES. The RESOLUTE clinical program: one month DAPT data presented atTCT 2012 in Miami, Florida 57