Prolonged Dual Antiplatelet Therapy Research Articles

Personalising the decision for prolonged dual antiplatelet therapy: development, validation and potential impact of prognostic models for cardiovascular events and bleeding in myocardial infarction survivors.

AimsThe aim of this study is to develop models to aid the decision to prolong dual antiplatelet therapy (DAPT) that requires balancing an individual patient’s potential benefits and harms.Methods and resultsUsing population-based electronic health records (EHRs) (CALIBER, England, 2000–10), of patients evaluated 1 year after acute myocardial infarction (MI), we developed (n = 12 694 patients) and validated (n = 5613) prognostic models for cardiovascular (cardiovascular death, MI or stroke) events and three different bleeding endpoints. We applied trial effect estimates to determine potential benefits and harms of DAPT and the net clinical benefit of individuals. Prognostic models for cardiovascular events (c-index: 0.75 (95% CI: 0.74, 0.77)) and bleeding (c index 0.72 (95% CI: 0.67, 0.77)) were well calibrated: 3-year risk of cardiovascular events was 16.5% overall (5.2% in the lowest- and 46.7% in the highest-risk individuals), while for major bleeding, it was 1.7% (0.3% in the lowest- and 5.4% in the highest-risk patients). For every 10 000 patients treated per year, we estimated 249 (95% CI: 228, 269) cardiovascular events prevented and 134 (95% CI: 87, 181) major bleeding events caused in the highest-risk patients, and 28 (95% CI: 19, 37) cardiovascular events prevented and 9 (95% CI: 0, 20) major bleeding events caused in the lowest-risk patients. There was a net clinical benefit of prolonged DAPT in 63–99% patients depending on how benefits and harms were weighted.ConclusionPrognostic models for cardiovascular events and bleeding using population-based EHRs may help to personalise decisions for prolonged DAPT 1-year following acute MI.

The optimal discontinuation of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention with drug-eluting stents: A meta-analysis of randomized trials

BackgroundCurrent guidelines recommend prolonged dual antiplatelet therapy (DAPT) for patients with drug-eluting stents (DES) implantation. Nevertheless, optimal discontinuation of DAPT remains a controversy. We performed a meta-analysis of all randomized controlled trials (RCTs) that evaluate optimal discontinuation of DAPT in patients undergoing percutaneous coronary intervention (PCI) with DES. MethodsWe searched electronic databases including PubMed, Cochrane Library, EMBASE and ClinicalTrials.gov from database RCTs that reported different modes of discontinuation of DAPT in patients with DES. The primary endpoints were all-cause death, cardiovascular death, myocardial infarction (MI) and probably or definite stent thrombosis (ST). Secondary endpoints were repeat revascularization, stroke, major bleeding and net adverse clinical events (NACE). ResultsWe included 13 RCTs meeting the criteria with a total of 36,749 patients. No significant difference was observed in all-cause death (RR [95% CI]=0.87 [0.75, 1.01], P=0.07, I2=0%), cardiovascular death (RR [95% CI]=0.97 [0.79, 1.19], P=0.76, I2=0%), repeat revascularization (RR [95% CI]=1.07 [0.92, 1.25], P=0.36, I2=0%), and stroke (RR [95% CI]=1.01 [0.80, 1.28], P=0.94, I2=0%). Compared with shorter DAPT, longer DAPT was associated with a significant reduction in MI (RR [95% CI]=1.46 [1.26, 1.69], P<0.00001, I2=28%) and ST (RR [95% CI]=1.93 [1.45, 2.58], P<0.00001, I2=32%), and a significant increase in major bleeding (RR [95% CI]=0.60 [0.49, 0.74], P<0.00001, I2=0%). However, there was no difference in NACE (RR [95% CI]=1.03 [0.91, 1.17], P=0.63, I2=0%). In subgroup analyses based on stent type, we demonstrated that longer DAPT was associated with a significant reduction in thrombotic events (MI and ST) after first-generation DES implantation (RR [95% CI]=2.58 [1.85, 3.58], I2=0%) and everolimus-eluting stents (EES, RR [95% CI]=1.54 [1.12, 2.11], I2=0%). Conversely, there was no difference in thrombotic events in patients with zotarolimus-eluting stents (ZES, RR [95% CI]=1.17 [0.83, 1.63], I2=75%) and biodegradable polymer DES (BP-DES, RR [95% CI]=1.15 [0.74, 1.79]). Conclusions1) Compared with shorter DAPT, longer DAPT was associated with a significant reduction in thrombotic events (MI and ST) and a higher rate of major bleeding. 2) By the assessment of the trade-off between thrombotic and hemorrhagic events, shorter DAPT was non-inferior to longer DAPT. 3) The benefit of longer DAPT was significant in patients with first-generation DES and EES and weakened with other second-generation DES (ZES and BP-DES).

A prospective, randomized, open-label trial of 6-month versus 12-month dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction: Rationale and design of the “DAPT-STEMI trial”

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors. Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required. The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT.

Single or dual antiplatelet therapy after PCI.

The optimal duration and type of antiplatelet therapy after implantation of a drug-eluting stent (DES) remains uncertain. At the time of the first-in-man implantation of the sirolimus DES in 1999, the protocol-defined dual antiplatelet therapy (DAPT) duration was only 2 months. Subsequently, DAPT duration was extended to 1 year on the basis of anecdotal historical data, and this practice was then incorporated into clinical guidelines. For >1 decade, trialists have sought to compare the safety and efficacy of abbreviated (<6 months) and prolonged (>12 months) DAPT regimens. However, the body of evidence is limited by the heterogeneity of end points, time of randomization, and bleeding criteria used in each trial. Pharmaceutical advances led to the introduction of new ADP-receptor antagonists, which are thought to be more effective than clopidogrel. The ADP-receptor antagonists moved the focus from the optimal duration of DAPT to the potential efficacy of single antiplatelet therapy after DES implantation. In this Review, we summarize the current evidence on the duration of DAPT and the risk of bleeding and adverse cardiac events after DES implantation, and describe the pitfalls of trial interpretation. The ongoing, prospective trials to test single antiplatelet therapy after DES implantation are also discussed.

CRT-100.62 High Bleeding Risk Influences the Use of Metallic Stents

Patients undergoing percutaneous coronary intervention (PCI) with Drug eluting stents (DES) are subject to prolonged dual antiplatelet therapy (DAPT) which can lead to increase in bleeding rate in high bleed risk (HBR) population. The aimof this study is to examine the effect of HBR on the

Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients.

We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify the optimal duration of DAPT after DES in individual patients based on their relative ischaemic and bleeding risks.

Secondary prevention with antiplatelet therapy in cardiac rehabilitation

The long-term increased cardiovascular risk of patients with an acute coronary syndrome (ACS) is a challenging and common clinical problem. Recent evidence demonstrated an ischemic benefit for a prolonged dual antiplatelet therapy beyond the initial 12 months at the cost of an increased bleeding risk. Individual, careful and repeated risk-benefit analyses are essential for an optimized patient management in which cardiovascular rehabilitation providers may play a central role.

Drug-Eluting vs. Bare-Metal Stents: Is it a Matter of Vessel Size?

Background: Although drug-eluting stents (DES) for percutaneous coronary intervention have dramatically reduced the incidence of in-stent restenosis, their deployment for large-size coronary lesions is still controversial because of problems such as prolonged dual antiplatelet therapy, late in-stent thrombosis and costs. Aim: This study sought to evaluate the safety and effectiveness of drug-eluting stents (DES) compared to baremetal stents (BMS) for patients with large coronary vessels ≥ 3.5 mm. Methods: This is a retrospective case-control comparative study conducted in the cardiology A department of the university hospital Fattouma Bourguiba in Monastir. A total of 77 consecutive patients (80 lesions) who underwent, between October 2003 and March 2014, successfully DES implantation were compared to 73 consecutive patients (84 lesions) who were treated with BMS in large coronary vessels ≥ 3.5 mm. Results: The average age in our population was 59.7 ± 11.3 years with a male majority without any significant difference between the two groups. The DES group contained significantly more patients with diabetes (67.5% vs. 38.1%; p<0.0001) and a history of coronary heart disease (40% vs. 16.7%; p=0.001). The BMS group had significantly more procedures in the aftermath of MI (18.8% vs. 40.5%; p=0.002) including more primary angioplasty (6.7% against 47.1%; p=0.006). About two-thirds of the study patients had multi-vessel disease with equal distribution in both groups. The average duration of dual antiplatelet therapy was significantly prolonged in the DES group: 13.01 ± 8.31 months vs. 7.59 ± 8.19 months; p<0.0001. A mean follow of 27.87 ± 14.82 months was obtained. At 12 months, DES led to a significant reduction in the combined rate of major cardiac events by about 70% (OR=0.32; 95% CI: 0.119 to 0.858; p=0.019) without allowing a significant reduction in the rates of in-stent restenosis, in-stent thrombosis, target vessel revascularization or non-combined major cardiac events. During longterm follow-up, the benefit of DES in terms of MACE was maintained by allowing a 60% reduction in the combined rate of major cardiac events (OR=0.406; 95% CI: 0.172 to 0.955; p=0.035). Multivariate analysis identified the BMS as an independent predictor of major cardiac events and death. However, the type of stent does not appear as a factor influencing the ISR and target lesion revascularization rates. Conclusion: The results of our study demonstrate a clear clinical benefit of drug-eluting stents during angioplasty of large coronary arteries in reducing major cardiac events and death without having any effect on in-stent restenosis, in-stent thrombosis nor target lesion revascularization.

Dual antiplatelet therapy and non-cardiac surgery: evolving issues and anesthetic implications

Dual antiplatelet therapy (DAPT) consisting of aspirin plus a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) is imperative for the treatment of acute coronary syndrome, particularly during the re-endothelialization period after percutaneous coronary intervention (PCI). When patients undergo surgery during this period, the consequences of stent thrombosis are far more serious than those of bleeding complications, except in cases of intracranial surgery. The recommendations for perioperative DAPT have changed with emerging evidence regarding the improved efficacy of non-first-generation drug (everolimus, zotarolimus)-eluting stents (DES). The mandatory interval of 1 year for elective surgery after DES implantation was shortened to 6 months (3 months if surgery cannot be further delayed). After this period, it is generally recommended that the P2Y12 inhibitor be stopped for the amount of time necessary for platelet function recovery (clopidogrel 5–7 days, prasugrel 7–10 days, ticagrelor 3–5 days), and that aspirin be continued during the perioperative period. In emergent or urgent surgeries that cannot be delayed beyond the recommended period after PCI, proceeding to surgery with continued DAPT should be considered. For intracranial procedures or other selected surgeries in which increased bleeding risk may also be fatal, cessation of DAPT (possibly with continuation or minimized interruption [3–4 days] of aspirin) with bridge therapy using short-acting, reversible intravenous antiplatelet agents such as cangrelor (P2Y12 inhibitor) or glycoprotein IIb/IIIa inhibitors (tirofiban, eptifibatide) may be contemplated. Such a critical decision should be individually tailored based on consensus among the anesthesiologist, cardiologist, surgeon, and patient to minimize both ischemic and bleeding risks.

PROLONGED DUAL ANTIPLATELET THERAPY AFTER MYOCARDIAL INFARCTION: WHAT THE RESULTS OF THE PEGASUS-TIMI 54 TRIAL SHOW

Prerequisites for the prolonged dual antiplatelet therapy after myocardial infarction are presented. The results of a large randomized placebo-controlled PEGASUS-TIMI 54 trial on the evaluation of efficacy and safety of prolonged use of a combination of acetylsalicylic acid and blocker P2Y12 platelet receptor, ticagrelor, in patients with high risk of thrombotic complications of atherosclerosis with a history of myocardial infarction 1-3 years ago are considered. The contribution of the results of this clinical trial in the modern understanding of the optimal use of antiplatelet agents in patients after myocardial infarction is analyzed.

Discontinuation of prolonged dual antiplatelet therapy for a dental extraction; A nearly-fatal decision

Stent thrombosis remains one of the most feared complications in patients with multiple stents implanted. In this clinical setting, optimal upfront dual antiplatelet therapy (DAPT) duration still remains controversial. Herein, we wish to report a case of life-threatening very-late stent thrombosis after DAPT temporary discontinuation, highlighting the prolonged increased thrombotic risk of complex angioplasty, even in otherwise low-ischemic risk patients according to recent recommendations. Our data are in line with novel information and might be useful in the pre-operative management of patients with complex percutaneous coronary intervention (PCI).

Optimal duration of dual anti-platelet therapy after percutaneous coronary intervention: 2016 consensus position of the Italian Society of Cardiology.

Definition of the optimal duration of dual anti-platelet therapy (DAPT) is an important clinical issue, given the large number of patients having percutaneous coronary intervention (PCI), the costs and risks of pharmacologic therapy, the consequences of stent thrombosis, and the potential benefits of DAPT in preventing ischaemic outcomes beyond stent thrombosis. Nowadays, the rationale for a prolonged duration of DAPT should be not only the prevention of stent thrombosis, but also the prevention of ischaemic events unrelated to the coronary stenosis treated with index PCI. A higher predisposition to athero-thrombosis may persist for years after an acute myocardial infarction, and even stable patients with a history of prior myocardial infarction are at high risk for major adverse cardiovascular events. Recently, results of pre-specified post-hoc analyses of randomized clinical trials, including the PEGASUS-TIMI 54 trial, have shed light on strategies of DAPT in various clinical situations, and should impact the next rounds of international guidelines, and also routine practice. Accordingly, the 2015 to 2016 the Board of the Italian Society of Cardiology addressed newer recommendations on duration of DAPT based on most recent scientific information. The document states that physicians should decide duration of DAPT on an individual basis, taking into account ischaemic and bleeding risks of any given patient. Indeed, current controversy surrounding optimal duration of DAPT clearly reflects the fact that, nowadays, a one size fits all strategy cannot be reliably applied to patients treated with PCI. Indeed, patients usually have factors for both increased ischaemic and bleeding risks that must be carefully evaluated to assess the benefit/risk ratio of prolonged DAPT. Personalized management of DAPT must be seen as a dynamic prescription with regular re-evaluations of the risk/benefit to the patient according to changes in his/her clinical profile. Also, in order to derive more benefit than harm from new treatments, a multi-parametric approach using several risk scores of the ischaemic and bleeding risks might improve the process of risk factor characterization. In patients with high ischaemic risk, particularly those with a history of myocardial infarction, the benefits of extended DAPT (particularly with ticagrelor up to 3 years) are likely to outweigh the risks.

Long-term effect of stents eluting 6-mercaptopurine in porcine coronary arteries.

BackgroundDrug-eluting stents (DES) have dramatically reduced restenosis rates compared to bare metal stents and are widely used in coronary artery angioplasty. The anti-proliferative nature of the drugs reduces smooth muscle cell (SMC) proliferation effectively, but unfortunately also negatively affects endothelialization of stent struts, necessitating prolonged dual anti-platelet therapy. Cell-type specific therapy may prevent this complication, giving rise to safer stents that do not require additional medication. 6-Mercaptopurine (6-MP) is a drug with demonstrated cell-type specific effects on vascular cells both in vitro and in vivo, inhibiting proliferation of SMCs while promoting survival of endothelial cells. In rabbits, we demonstrated that DES locally releasing 6-MP during 4 weeks reduced in-stent stenosis by inhibiting SMC proliferation and reducing inflammation, without negatively affecting endothelialization of the stent surface. The aim of the present study was to investigate whether 6-MP-eluting stents are similarly effective in preventing stenosis in porcine coronary arteries after 3 months, in order to assess the eligibility for human application.Methods6-MP-eluting and polymer-only control stents (both n = 7) were implanted in porcine coronary arteries after local balloon injury to assess the effect of 6-MP on vascular lesion formation. Three months after implantation, stented coronary arteries were harvested and analyzed.ResultsMorphometric analyses revealed that stents were implanted reproducibly and with limited injury to the vessel wall. Unexpectedly, both in-stent stenosis (6-MP: 41.1 ± 10.3 %; control: 29.6 ± 5.9 %) and inflammation (6-MP: 2.14 ± 0.51; control: 1.43 ± 0.45) were similar between the groups after 3 months.ConclusionIn conclusion, although 6-MP was previously found to potently inhibit SMC proliferation, reduce inflammation and promote endothelial cell survival, thereby effectively reducing in-stent restenosis in rabbits, stents containing 300 μg 6-MP did not reduce stenosis and inflammation in porcine coronary arteries.

Impact of stent type and prolonged dual antiplatelet therapy on long-term clinical outcomes in hemodialysis patients with coronary artery disease.

The aim of this study was to address 7-year clinical outcomes and impact of prolonged dual antiplatelet therapy (DAPT) after coronary stenting in hemodialysis patients. Our study included 123 consecutive hemodialysis patients who had undergone percutaneous coronary intervention with a drug-eluting stent (DES) or bare-metal stent (BMS) (DES: 64, BMS: 59) in our institution. We compared long-term clinical outcomes following DES with BMS implantation as well as clinical outcomes in patients on DAPT for ≥1year (DAPT on group, 89) with those on DAPT for <1year (DAPT off group, 34). We evaluated bleeding events and major adverse cardiac events (MACE), including cardiac death, non-fatal myocardial infarction, target vessel revascularization, and stent thrombosis. At 1year after stenting, the incidence of MACE was significantly lower in the DES group than in the BMS group (DES versus BMS: 33.2 versus 51.8%; p=0.045). However, this advantage of DES disappeared by the 7th year (DES versus BMS: 66.0 versus 70.0%; p=0.42). The cumulative incidence of MACE beyond 1year was significantly higher in the DAPT on group than in the DAPT off group (DAPT on versus DAPT off: 51.3 versus 18.5%; p=0.047). The bleeding events in the DAPT on group were 5.1 times greater than in the DAPT off group (DAPT on versus DAPT off: 16.4 versus 3.2%; p=0.06). Use of DES and prolonged DAPT did not improve 7-year clinical outcomes in hemodialysis patients with coronary artery disease.

Antiplatelet therapy in patients with glucose-6-phosphate dehydrogenases deficiency after percutaneous coronary intervention: A reappraisal for clinical and interventional cardiologists

Glucose-6-phosphate dehydrogenase (G6PD) deficiency represents one of the most common erythrocyte enzymopathy. In the era of drug-eluting stents (DESs), the use of prolonged dual antiplatelet therapy (DAPT) with aspirin (ASA) and thienopyridine (clopidogrel or ticlopidine) has become mandatory in the treatment of patients with acute coronary syndromes (ACS) and/or after percutaneous coronary intervention (PCI). However, the use of ASA, and more in general of antiplatelet drugs in patients with G6PD deficiency remains controversial, also for the absence of specific guidelines and scientific evidences. In the present manuscript, we reviewed the few cases available in medical literature, regarding patients with G6PD deficiency treated with percutaneous coronary artery intervention (PCI) and DAPT, with the aim to discuss and clarify the optimal treatment in these patients.

Dual Antiplatelet Therapy and Clinical Outcomes after Coronary Drug-Eluting Stent Implantation in Patients on Hemodialysis.

We aimed to investigate the benefits and risks of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent (DES) implantation in patients undergoing hemodialysis. A nested case-control analysis of patients on hemodialysis after receipt of DES and DAPT treatment was conducted using data from Taiwan's National Health Insurance Research Database for the period 2007-2011. Cases of myocardial infarction or death within 1 year after DES implantation were matched one-to-one with control patients. Odds ratios were calculated to compare DAPT continuation with discontinuation. Additionally, a propensity score-adjusted 6-month landmark cohort analysis was also conducted to evaluate the long-term benefits and risks of prolonged (>6 months) compared with ≤6 months of DAPT use. The primary outcomes were death and myocardial infarction. The secondary outcomes were ischemic stroke, revascularization, and major bleeding. In the nested case-control analysis, patients who continued DAPT had a lower rate of death or myocardial infarction within 1 year after receipt of a DES (adjusted odds ratio, 0.54; 95% confidence interval, 0.36 to 0.81; P=0.003), whereas this association became statistically nonsignificant when compared with patients who discontinued DAPT for the period between 6 and 12 months after receipt of a DES (adjusted odds ratio, 1.51; 95% confidence interval, 0.75 to 3.04). In the propensity score-adjusted cohort analysis, >6 months of DAPT use was not associated with different primary or secondary outcomes than shorter-term use. Our findings support that the clinical effectiveness of extended DAPT in a hemodialysis population may be tempered after 6 months post-DES implantation.

Long-term outcomes in patients with acute coronary syndromes related to prolonging dual antiplatelet therapy more than 12 months after coronary stenting.

To assess the impact of stent type on the risk of death or myocardial infarction (MI) related to dual antiplatelet therapy (DAPT) more than 12 months (prolonged DAPT) versus 12 or less months after PCI for an acute coronary syndrome (ACS). The recent DAPT study reported lower recurrent ischemic events from prolonged DAPT in patients treated with PCI for an ACS, but was underpowered to determine the impact of stent type. We determined clinical outcomes after PCI for an ACS (median follow-up: DES = 26 months, BMS = 46 months) in 18,484 patients in the Veterans Affairs system treated with first generation drug-eluting stents (DES) or bare-metal stents (BMS). We used landmark analyses starting 1 year after the index PCI to assess the risk of prolonged DAPT on the primary endpoint of death or MI. Multivariable and propensity models adjusted for confounding. There was a significant interaction between stent type and prolonged DAPT for death and MI (P = 0.0036), death (P = 0.054), and major bleeding (P = 0.0013). Patients treated with prolonged DAPT had lower risks of death or MI (HR = 0.71, 95% CI = 0.61, 0.82) and death (HR = 0.74, 95%CI = 0.62, 0.89) with DES, but not BMS, and higher risks of major bleeding, particularly with BMS (HR = 1.67, P < 0.001) than DES (HR = 1.24, p = 0.01). Prolonging DAPT more than 12 months after PCI for ACS only associated with a lower risk of ischemic events in the 1-4 years after PCI in those receiving first generation DES. Stent type may influence the benefit of prolonged DAPT. © 2016 Wiley Periodicals, Inc.

How long should dual antiplatelet therapy be used in diabetic patients after implantation of drug-eluting stents?

To analyze evidence from randomized clinical trials (RCTs) that identifies the optimal duration of dual antiplatelet therapy (DAPT) after implantation of newer generation drug-eluting stents (DESs) in diabetic patients. Patients with diabetes mellitus have increased risk of ischemic events and bleeding after DES implantation. The optimal duration of DAPT for this population is currently unknown. In a subgroup analysis of 8542 diabetic patients enrolled in eight RCTs of DAPT duration after implantation of newer generation DESs, prolonged courses of DAPT of 12-36 months in duration resulted in rates of major adverse cardiac events that were no different from those seen after shorter courses of DAPT of 3-12 months in duration (odds ratio 1.00, 95% Bayesian credible interval 0.74-1.33). Prolonged DAPT up to 36 months after newer generation DES implantation in diabetic subgroups has not been associated with better outcomes than shorter courses of 3-12 months. Until dedicated trials are completed in diabetic populations, DAPT duration after newer generation DES implantation in patients with diabetes mellitus should follow recommendations for the general population.

Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial

No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a result of recovered vasomotion of the scaffolded vessel. The ABSORB II trial is a prospective, randomised, active-controlled, single-blind, parallel two-group, multicentre clinical trial. We enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients (2:1) to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb; Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. At 3 year follow-up, the primary endpoint was superiority of the Absorb bioresorbable scaffold versus the Xience metallic stent in angiographic vasomotor reactivity after administration of intracoronary nitrate. The co-primary endpoint is the non-inferiority of angiographic late luminal loss. For the endpoint of vasomotion, the comparison was tested using a two-sided t test. For the endpoint of late luminal loss, non-inferiority was tested using a one-sided asymptotic test, against a non-inferiority margin of 0·14 mm. The trial is registered at ClinicalTrials.gov, number NCT01425281. Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the Absorb group (335 patients, 364 lesions) or the Xience group (166 patients, 182 lesions). The vasomotor reactivity at 3 years was not statistically different (Absorb group 0·047 mm [SD 0·109] vs Xience group 0·056 mm [0·117]; psuperiority=0·49), whereas the late luminal loss was larger in the Absorb group than in the Xience group (0·37 mm [0·45] vs 0·25 mm [0·25]; pnon-inferiority=0·78). This difference in luminal dimension was confirmed by intravascular ultrasound assessment of the minimum lumen area (4·32 mm2 [SD 1·48] vs 5·38 mm2 [1·51]; p<0·0001). The secondary endpoints of patient-oriented composite endpoint, Seattle Angina Questionnaire score, and exercise testing were not statistically different in both groups. However, a device-oriented composite endpoint was significantly different between the Absorb group and the Xience group (10% vs 5%, hazard ratio 2·17 [95% CI 1·01-4·70]; log-rank test p=0·0425), mainly driven by target vessel myocardial infarction (6% vs 1%; p=0·0108), including peri-procedural myocardial infarction (4% vs 1%; p=0·16). The trial did not meet its co-primary endpoints of superior vasomotor reactivity and non-inferior late luminal loss for the Absorb bioresorbable scaffold with respect to the metallic stent, which was found to have significantly lower late luminal loss than the Absorb scaffold. A higher rate of device-oriented composite endpoint due to target vessel myocardial infarction, including peri-procedural myocardial infarction, was observed in the Absorb group. The patient-oriented composite endpoint, anginal status, and exercise testing, were not statistically different between both devices at 3 years. Future studies should investigate the clinical impact of accurate intravascular imaging in sizing the device and in optimising the scaffold implantation. The benefit and need for prolonged dual antiplatelet therapy after bioresorbable scaffold implantation could also become a topic for future clinical research. Abbott Vascular.

TCT-209 Optimal duration of dual antiplatelet therapy after left main coronary artery stenting: A retrospective multicenter AOI LMCA stenting registry

Several studies suggested that prolonged dual antiplatelet therapy (DAPT) reduced the risks of ischemic events, but increased the risk of bleeding. Optimal duration of DAPT after left main coronary artery (LMCA) stenting remains unclear. From Nov. 2004 to Dec. 2012, we enrolled consecutive 1809