Dual Antiplatelet Therapy Cessation Research Articles

Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study

Dual antiplatelet therapy (DAPT) cessation increases the risk of adverse events after percutaneous coronary intervention (PCI). Whether risk changes over time, depends on the underlying reason for DAPT cessation, or both is unknown. We assessed associations between different modes of DAPT cessation and cardiovascular risk after PCI. The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010. Adult patients (aged 18 years or older) undergoing successful stent implantation in one or more native coronary artery and discharged on DAPT were eligible for enrolment. Patients were followed up at months 1, 6, 12, and 24 after implantation. Prespecified categories for DAPT cessation included physician-recommended discontinuation, brief interruption (for surgery), or disruption (non-compliance or because of bleeding). All adverse events and episodes of DAPT cessation were independently adjudicated. Using Cox models with time-varying covariates, we examined the effect of DAPT cessation on major adverse events (MACE [composite of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularisation]). Incidence rates for DAPT cessation and adverse events were calculated as Kaplan-Meier estimates of time to the first event. This study is registered with ClinicalTrials.gov, number NCT00998127. We enrolled 5031 patients undergoing PCI, including 5018 in the final study population. Over 2 years, the overall incidence of any DAPT cessation was 57·3%. Rate of any discontinuation was 40·8%, of interruption was 10·5%, and of disruption was 14·4%. The corresponding overall 2 year MACE rate was 11·5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1·41 (95% CI 0·94-2·12; p=0·10) and to disruption was 1·50 (1·14-1.97; p=0·004). Within 7 days, 8-30 days, and more than 30 days after disruption, adjusted HRs were 7·04 (3·31-14·95), 2·17 (0·97-4·88), and 1·3 (0·97-1·76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0·63 [0·46-0·86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE definition that did not include target lesion revascularisation. In a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type. Bristol-Myers Squibb and Sanofi-Aventis.

Antiplatelet therapy after coronary stenting: for how long?

Dual antiplatelet therapy (DAPT) with aspirin and an oral P2Y12 receptor blocker is the standard regimen to prevent atherothrombotic events in patients after percutaneous coronary stenting. 1 Wijns W Kolh P Danchin N et al. Guidelines on myocardial revascularization. Eur Heart J. 2010; 31: 2501-2555 Crossref PubMed Scopus (26) Google Scholar Although the prevalence is low in terms of numbers, the consequences of stent thrombosis are severe with a 64% rate of death or myocardial infarction and a mortality rate of 9–45%. 2 Iakovou I Schmidt T Bonizzoni E et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005; 293: 2126-2130 Crossref PubMed Scopus (2924) Google Scholar , 3 Cutlip DE Baim DS Ho KK et al. Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation. 2001; 103: 1967-1971 Crossref PubMed Scopus (821) Google Scholar The risk of stent thrombosis is difficult to assess in patients who need to cease treatment with DAPT, and the possibility of stent thrombosis causes much anxiety in patients awaiting DAPT. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational studyIn a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type. Full-Text PDF

PREDICTORS OF DUAL ANTIPLATELET THERAPY NON-ADHERENCE AFTER PCI: ONE-YEAR INSIGHTS FROM THE PARIS REGISTRY

Demographic and socioclinical factors affect adherence to dual anti-platelet therapy (DAPT) after percutaneous coronary intervention (PCI). DAPT cessation has been shown to increase stent thrombosis risk, recurrent myocardial infarction, and death. We investigated correlates of DAPT non-adherence

IMPACT OF GENDER ON PATTERNS OF DUAL ANTIPLATELET THERAPY CESSATION AND NON-ADHERENCE: ONE-YEAR RESULTS FROM THE PATTERNS OF NON-ADHERENCE TO ANTI-PLATELET REGIMENS IN STENTED PATIENTS (PARIS), AN OBSERVATIONAL SINGLE-ARM STUDY

Multiple clinical and sociodemographic factors are associated with adherence to dual antiplatelet therapy (DAPT) post percutaneous coronary intervention (PCI). Studies have shown women to have higher rates of adverse events after PCI. Whether this increased risk is attributable to DAPT cessation is

Women, Bleeding, and Coronary Intervention

Bleeding initiates a cascade of events that increase morbidity and mortality among patients undergoing percutaneous coronary intervention (PCI).1–5 Acute loss of blood impacts circulatory volume and can potentiate and perpetuate shock. In addition, bleeding leads to anemia and transfusion of blood products, which promote inflammation and untoward cardiovascular effects, especially in the setting of acute coronary syndrome.6–8 Finally, bleeding results in cessation of dual antiplatelet therapy, which increases risk of recurrent ischemic events such as stent thrombosis and myocardial infarction.9,10 Registries and randomized trials have shown the impact of bleeding on outcomes. Patient in the Global Registry of Acute Coronary Events were noted to have a 4.0% incidence of major bleeding across the spectrum of acute coronary syndrome (ACS). Furthermore, major bleeding was an independent predictor of in-hospital mortality (adjusted odds ratio, 1.64 [95% confidence interval, 1.18-2.28]).11 Ndrepepa et al2 evaluated 4 randomized control trials of patients undergoing PCI and identified major bleeding as the strongest independent predictor of 1-year mortality. Similarly, Mehran et al12 performed a patient level pooled analysis of >17 000 patients in 3 ACS trials: the occurrence of a major bleed within 30 days of hospitalization was associated with a 4-fold higher risk of mortality at 1 year. Finally, in patients with ST segment elevation myocardial infarction enrolled in the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction trial, bleeding related to PCI was an independent predictor of mortality after 3 years of follow-up (hazard ratio, 2.80 [95% confidence interval, 1.89–4.16]).13 Increased focus on the morbidity and mortality associated with PCI-related bleeding has led to pharmacological, procedural, and technological advances,14 which have resulted in improvement in post-PCI bleeding rates over the past decade (Figure 1).15–18 The …

Benefit of Long-Term Dual Anti-Platelet Therapy in Patients Treated With Drug-Eluting Stents: From the NHLBI Dynamic Registry

The optimal duration of dual-antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is an important, unanswered question. This study was designed to evaluate the association of varying durations of DAPT on clinical outcomes after DES implantation for the treatment of coronary artery disease. Using the National Heart, Lung, and Blood Institute Dynamic Registry, patients enrolled in the last 2 waves after index percutaneous coronary intervention with DES and who were event free at the time of landmark analysis were included. Landmark analysis was performed 12 and 24 months after percutaneous coronary intervention, and patients were stratified according to continued use of DAPT or not. Subjects were evaluated for rates of death, myocardial infarction, and stent thrombosis at 4 years from their index procedures. The numbers of evaluable patients were 2,157 and 1,918 for the 12- and 24-month landmarks, respectively. In both landmark analyses, there was a significantly lower 4-year rate of death or myocardial infarction in the group that continued DAPT compared to the group that did not (12 months: 10.5% vs 14.5%, p=0.01; 24 months: 5.7% vs 8.6%, p= 0.02). Beneficial differences in the group that continued on DAPT were preserved after multivariate and propensity adjustment. There were no significant differences in definite stent thrombosis in either landmark analysis. In conclusion, at 12 and 24 months after DES implantation, continued use of DAPT was associated with lower 4-year risk for death and myocardial infarction.

Clinical expert consensus statement on best practices in the cardiac catheterization laboratory: Society for cardiovascular angiography and interventions

The cardiac catheterization laboratory (CCL) is a setting in which elective, urgent, and emergent percutaneous procedures are performed. This poses challenges to maintaining and prioritizing high quality care and patient safety. Nonetheless, process expectations of a high-quality CCL include appropriate periprocedural communication, clinical management, documentation, and universal protocol. Regulations primarily targeted at open surgical operating rooms have the potential to negatively impact care because they may mandate focus on performance measures that are not necessarily relevant to the cardiac catheterization laboratory. For example, routine site marking for percutaneous access is irrelevant for most patients since failure to obtain access on one side (e.g., right femoral artery) simply leads to attempting access on the other side (e.g., left femoral artery). Instead, directives should be tailored to the percutaneous procedure setting to assure quality and optimal patient safety. This document will therefore provide expert consensus opinion on a number of issues pertaining to ‘‘best practices’’ within the CCL, focusing on quality and safety during each step of the process. The writing committee acknowledges a dearth in high-quality published studies in this area, making many of the enclosed recommendations based primarily on expert consensus. Although references are provided when available, further research specifically in catheterization laboratory processes and quality improvement is needed. The document is divided into ‘‘best practices’’ that should be performed during the preprocedure, intraprocedure, and postprocedure settings for diagnostic cardiac catheterization and coronary intervention, to be consistent with the typical patient flow into and out of the CCL. Despite the long history of cardiac catheterization that dates back several decades, a document describing these ‘‘best practices’’ has not yet been written. The purpose of this document is not to represent all acceptable practices, but to provide consensus opinion on what would currently be considered ‘‘best practices’’ as future goals for catheterization laboratories.

Duration of dual antiplatelet therapy and outcomes after coronary stenting with the genous™ bio‐engineered R stent™ in patients from the e‐healing registry

We investigated the relation between duration of dual antiplatelet therapy (DAPT) and clinical outcomes up to 12 months after Genous™ endothelial progenitor cell capturing R stent™ placement in patients from the e-HEALING registry. Cessation of (DAPT) has been shown to be associated with the occurrence of stent thrombosis (ST). After Genous placement, 1 month of DAPT is recommended. Patients were analyzed according to continuation or discontinuation of DAPT at a 30-day and 6-month landmark, excluding patients with events before the landmark. Each landmark was a new baseline, and outcomes were followed up to 12 months after stenting. The main outcome for our current analysis was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction and target vessel revascularization. Secondary outcomes included ST. (Un)adjusted hazard ratios (HR) for TVF were calculated with Cox regression. No difference was observed in the incidence of TVF [HR: 1.03; 95% confidence intervals (CI): 0.65-1.65, P = 0.89] in patients continuing DAPT (n = 4,249) at 30 days versus patients stopped (n = 309), and HR: 0.82 (95% CI: 0.55-1.23, P = 0.34) in patients continuing DAPT (n = 2,654) at 6 months versus patients stopped [n = 1,408] DAPT). Furthermore, no differences were observed in ST. Even after addition of identified independent predictors for TVF, adjusted TVF hazards were comparable. In a post-hoc analysis of e-HEALING, duration of DAPT was not associated with the occurrence of the outcomes TVF or ST. The Genous stent may be an attractive treatment especially in patients at increased risk for (temporary) cessation of DAPT or bleeding.

Initial Experience With an Institutional Bridging Protocol for Patients With Recent Coronary Stent Implantation Requiring Discontinuation of Dual Antiplatelet Therapy Resulting From Urgent Surgery

Patients that receive coronary bare-metal or drug-eluting stents have to be maintained on dual antiplatelet therapy (DAPT) for at least 4 weeks or 12 months, respectively. The prolonged time period required for drug-eluting stents is the result of delayed vascular healing that is associated with the drug and the polymeric coating. Premature cessation of DAPT may precipitate life-threatening stent thrombosis. However, some urgent, unplanned surgical procedures cannot be carried out under DAPT as a result of an unacceptable bleeding risk. Therefore, in these particular patients, DAPT therapy needs to be bridged for urgent surgery to avoid stent thrombosis, yet no clinical recommendation about a specific pharmacologic protocol is currently available for this specific purpose. We report about the initial experience with a novel institutional bridging protocol using bivalirudin that has been developed and applied successfully in a limited number of patients.

Intracranial Stenting With Wingspan

See related articles, pages 1971–1975 and 1976–1981. Intracranial atherosclerotic disease (ICAD) is a major cause of stroke and yet there are no proven effective treatments for it. Medical therapy has been associated with a high rate of recurrence, particularly in those with the most severe stenoses who have a 22.5% risk of stroke or death in the first year after a stroke.1 Clearly better alternatives are needed. Surgical bypass has been shown in at least 1 trial to be worse than medical therapy in the era before thienopyridines, statins, and angiotensin-converting enzyme inhibitors. In this issue of Stroke , Fiorella and colleagues describe their longer-term experience with intracranial stenting with the Wingspan (Stryker Inc, Fremont, CA) stent system and last year in this Journal, Jiang and colleagues published their long-term experience with 100 consecutive patients also treated with the Wingspan stent system.2,3 The question is do these publications broaden our knowledge enough to alter management of patients with ICAD? Do they prove that endovascular therapy is superior to medical treatment and that it is safe enough to be performed routinely? The article by Fiorella et al represents the largest (N=158) published series of Wingspan in the United States to treat ≥50% symptomatic stenoses.2 The immediate perioperative stroke and death rates were 5.7% (N=9) and 2.5% (N=4), respectively. Over a mean follow-up period of 14.2 months (only 110 patients [69.6%] had 12 months of follow-up), the primary end point (any perioperative stroke or death and any ipsilateral stroke thereafter) was noted in 15.7% of patients or approximately 13.2%/year. Seventy-six percent of the ipsilateral strokes occurred within the first 6 months with no events beyond 12 months. These event rates did not include transient ischemic attacks (TIAs) and did not include target lesion revascularization (TLR) for …

TCT-112: Dual Antiplatelet Therapy Cessation due to Bleeding Complication is Related to Long-Term Clinical Outcome Following Percutaneous Coronary Intervention

TCT-112: Dual Antiplatelet Therapy Cessation due to Bleeding Complication is Related to Long-Term Clinical Outcome Following Percutaneous Coronary Intervention

Recurrent very late thrombosis of drug-eluting stent: Optical coherence tomography findings

Very late stent thrombosis (VLST) after implantation of a drug-eluting stent (DES) is a rare but catastrophic complication and the mechanisms are not completely understood. We describe a 76-year-old patient with recurrent VLST of DES that developed at 13 and 23 months after the initial catheter procedure of DES implantation under the cessation of dual antiplatelet therapy. Optical coherence tomography (OCT) observation revealed small stent area of a DES. Based on the OCT findings, balloon angioplasty for expansion of the DES was performed and angiographic Thrombolysis In Myocardial Infarction grade 3 flow was subsequently obtained. Small stent area is considered a significant factor in acute or subacute stent thrombosis according to previous reports. The present report shows that small stent area of DES may be regarded as a key factor in recurrent VLST as well as cessation of dual antiplatelet therapy.

AS-267: Primary Angioplasty for Definite Stent Thrombosis: A Relook at Our Cases

Stent thrombosis (ST) accounted for 3.6% of emergency percutaneous coronary intervention (PCI) procedures as reported by the OPTIMIST study. The clinical circumstances producing ST differ depending on the type of stent initially implanted to cessation of dual antiplatelet therapy (DAPT). As per the ARC definition, definite ST requires angiographic confirmation of thrombus, associated with clinical or electrocardiographic signs of acute ischemia or elevation of cardiac enzymes.

Simultaneous late stent thrombosis in two coronary arteries following drug-eluting stent implantation

Late stent thrombosis has emerged as an infrequent but serious complication of drug-eluting stent (DES) implantation. Premature cessation of dual antiplatelet therapy is the most common risk factor for its occurrence. In the era of multivessel stenting with DES, there is a potential for multivessel late stent thrombosis following cessation of dual antiplatelet therapy. We present a rare case of a patient who sustained simultaneous late stent thromboses in DESs implanted in two coronary arteries as a result of premature cessation of dual antiplatelet therapy.

Drug-eluting stent thrombosis

Stent thrombosis is a rare complication following stent implantation; if it occurs, however, it is associated with a high morbidity and mortality. Despite reduced rates of restenosis, drug-eluting stents (DES) have not reduced the incidence of stent thrombosis as compared with bare-metal stents (BMS). Patient-, lesion-, and procedure-related factors as well as thrombogenicity of the stent itself are involved in the pathogenesis of stent thrombosis. Furthermore, early cessation of dual antiplatelet therapy correlates with an increased risk of stent thrombosis. This review focuses on clinical evidence and pathophysiological mechanisms of stent thrombosis with DES, particularly highlighting prothrombotic effects of the stent itself.

Safety in simple versus complex stenting of coronary artery bifurcation lesions. The Nordic Bifurcation Study 14-month follow-up results

The risk of stent thrombosis has been reported to increase with percutaneous coronary intervention (PCI) complexity. The present study reports the pre-specified secondary endpoint of a 14-month stent thrombosis and major adverse cardiac events in patients stented with a simple versus a complex bifurcation technique using sirolimus eluting stents (SES). A total of 413 patients with a coronary bifurcation lesion were randomised to a simple treatment strategy; stenting of main vessel and optional stenting of side branch (MV group), or to a complex stenting strategy; stenting of both main vessel and side branch (MV+SB group). Mortality data were available in all patients and 14-month clinical follow-up data in 395 (96%) of the patients. After 14 months, the rates of definite, probable and possible stent thrombosis (ARC criteria) were 1.0% vs. 0.5%, 1.0% vs. 0% and 0.5% vs. 0% (ns) in the MV and in the MV+SB groups, respectively. Rates of MACE were 9.5% in the MV group and 8.2% in the MV+SB group (ns). Total death was seen in 2.4% vs. 1.0% and non-PCI related myocardial infarction in 2.0% vs. 1.0% in the MV and the MV+SB groups, respectively. After 14 months, two months after recommended cessation of dual antiplatelet therapy, the rates of stent thrombosis and major adverse cardiac events were low and independent of treatment complexity in patients treated with SES for coronary artery bifurcation lesions.

Efficiency and safety of the sirolimus eluting stent in complex coronary artery lesions after cessation of dual antiplatelet therapy: fifteen months clinical outcome of the randomised Stenting Coronary Arteries in Non-stress/benestent Disease (SCANDSTENT) trial

The randomised Stenting Coronary Arteries in Non-stress/benestent Disease (SCANDSTENT) trial reported considerably less angiographic restenosis after implantation of sirolimus-eluting stents (SES) vs bare metal stents (BMS) in patients with complex coronary lesions. The purpose of this study was to evaluate the clinical outcome after a majority of the SCANDSTENT patients had stopped the dual antiplatelet therapy. The SCANDSTENT trial randomly assigned 322 patients with symptomatic complex coronary artery disease (occlusions, bifurcations, ostial or angulated lesions) to receive SES or BMS. At 15 months after stent implantation, when 80% of the patients had stopped taking clopidogrel, six patients in the SES group and 10 in the BMS group had died or suffered a myocardial infarction (non significant [NS]). Compared with BMS, SES reduced the rate of target vessel revascularisation (TVR) from 33.1% to 5.6% (P<0.001) and the frequency of major adverse cardiac events from 35.7% to 8.6% (p<0.001). Definite stent thrombosis was observed in five patients in the BMS group, and two cases of probable and possible stent thrombosis were observed in the SES group (NS). One case of possible SES thrombosis occurred more than one year after stent implantation. Compared with BMS, SES markedly reduced the frequency of TVR and MACE within 15 months in SCANDSTENT patients with complex coronary artery lesions without development of delayed restenosis.

Analysis of 36 Reported Cases of Late Thrombosis in Drug-Eluting Stents Placed in Coronary Arteries

Drug-eluting stents (DESs) have decreased the incidence of in-stent restenosis. Within the past 2 years several cases on late stent thrombosis (LST) have been reported. This study analyzed and reviewed all published cases of LST in DESs to explore possible trends not previously reported. We applied a Medline search using the key word "drug eluting stents." All 845 positive matches in March 2006 were screened for case reports of LST in DESs, defined as angiographic stent thrombosis >or=30 days after deployment. We included reported LSTs from randomized trials, observational registry reports, and letters to the editor if information regarding timing from stent deployment to clinical event, vessel, stent diameter and length, and antiplatelet regimen were available. There was no significant difference in the incidence of LST between sirolimus- and paclitaxel-eluting stents. Median time from stent deployment to clinical event was 242 days (total range 39 to 927). If aspirin and clopidogrel were discontinued, median time to clinical event was 7 days (3 to 150). In comparison, if only clopidogrel was discontinued, median time to clinical event was 30 days (14 to 690, p <0.0001). There was no significant difference in stent diameter and length between sirolimus- and paclitaxel-eluting stents. Forty-two percent of events occurred in relation to a surgical procedure for which the 2 antiplatelet agents or clopidogrel alone was discontinued. In conclusion, there was a strong association between occurrence of LST and cessation of dual antiplatelet therapy. Patients who continued on aspirin had a significant delay to the clinical event. Efforts should be made to maintain patients on aspirin during routine surgical procedures.