Longer Dual Antiplatelet Therapy Research Articles

Duration and clinical outcomes of dual antiplatelet therapy following percutaneous coronary intervention for acute coronary syndrome: A multicentre "real-world practice" registry-based study.

The optimal duration of dual antiplatelet therapy (DAPT) ought to be determined taking into account individual ischaemic or bleeding events risks. To date, studies have provided inconclusive evidence on the effects of prolonged DAPT. We sought to evaluate the long-term outcomes of this strategy following percutaneous revascularization in the context of acute coronary syndrome (ACS). Retrospectively from four centers in Madrid, we identified 750 consecutive ACS patients, divided in two groups of DAPT duration: <13 months and >13 months, with a mean follow-up of 48 months. Patients with DAPT > 13 months had a higher non-adjusted incidence of Major Adverse Cardiovascular Events (11.6% vs. 17.3%) and new revascularization (3.7% vs. 8.7%). Differences in all-cause death, cardiac death, myocardial infarction, stent thrombosis and stroke were non-significant. There was no difference in the incidence of major bleeding (7.4% vs. 6.3%). Multivariable Cox regression analysis showed that the independent risk predictors of MACE were age (HR: 1.04, 95% CI: 1.02-1.06, p < 0.001) and multivessel disease (HR: 2.29, 95% CI: 1.32-3.95, p = 0.003), whereas the independent protective predictor was normal hemoglobin (HR: 0.88, 95% CI: 0.78-0.98, p = 0.022). In this real-world registry cohort of ACS patients treated with PCI and 1 year of DAPT in Spain, we report a trend of increased rate of MACE and new revascularization not associated with TVR in patients with longer DAPT. Our findings support the need for future randomized controlled trials to confirm or refute these results.

Safety and efficacy of shortened dual antiplatelet therapy after complex percutaneous coronary intervention: A systematic review and meta-analysis

BackgroundOptimal duration of dual antiplatelet therapy (DAPT) in patients undergoing complex percutaneous coronary intervention (PCI) remains under investigation. Our aim is to compare shortened (≤3 months) DAPT with longer DAPT in patients undergoing complex PCIs. MethodsThree major databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) were screened. The primary endpoint was major bleedings as they are defined by the Bleeding Academic Research Consortium (BARC) 3–5. The secondary endpoints were major adverse cardiovascular events, all-cause and cardiovascular mortality, myocardial infarction, stroke, and stent thrombosis. ResultsFive studies were included in our analysis, with a total of 9,115 patients. Our meta-analysis met its primary endpoint, as abbreviated DAPT significantly reduced major bleedings by 43% (95% confidence intervals: 0.35–0.93). Ischemic events and mortality were not affected by the shortening of DAPT. ConclusionShortened DAPT significantly reduced the odds of major bleedings in patients undergoing complex PCI without increasing the ischemic events or mortality. Thus, it could be considered a safe and feasible option in such patients.

Abstract 11865: New Insights Into Optimal Duration of Dual Antiplatelet Therapy After Left Main Coronary Stenting: Findings From the Largest LM PCI Cohort

Background: The optimal duration of dual antiplatelet therapy (DAPT) and the risk-benefit ratio for long-term DAPT in patients with left main coronary artery disease (LMCAD) undergoing PCI remains uncertain. Objectives: The aim of this study was to assess the efficacy and safety of extended duration DAPT (&gt;12-month) versus ≤12-month DAPT in patients who received PCI for LMCAD. Methods: A total of 4,561 consecutive patients undergoing PCI and stenting of LMCAD at a single center from January 2004 to December 2016 were enrolled. The primary outcome was 3-year MACCE (death, myocardial infarction, stent thrombosis, or stroke). The key safety outcome was BARC 2, 3, or 5 bleeding at 3 years. Results: 3,865 patients free of major ischemic or bleeding events in the first 12 months were included in the primary analysis. The distal LM bifurcation disease was involved in 80.5% of cases, in whom 27.0% were treated with a 2-stent strategy. DAPT&gt;12-month (n=1,727) versus ≤12-month DAPT (n=2,138) was associated with a reduced risk of 3-year primary outcome (2.5% vs. 4.5%; adjusted HR [aHR]: 0.592, 95% CI: 0.414-0.948). Similar results were found for the other ischemic end points: all-cause mortality (0.9% vs. 3.0%; aHR: 0.315 [0.179-0.554]), cardiovascular mortality (0.5% vs. 1.6%; aHR: 0.354 [0.169-0.739]), myocardial infarction (0.8% vs. 1.9%; aHR: 0.451 [0.245-0.831]), and stent thrombosis (0.4% vs. 1.1%; aHR: 0.400 [0.171-0.936]). Long-term DAPT showed similar risks of BARC 2, 3, or 5 bleeding compared to short-term DAPT (1.8% vs. 1.6%; aHR: 1.109; 95% CI: 0.681-1.806). The lower risk of a net adverse clinical event (a composite of BARC 2, 3, or 5 bleeding and MACCE) was identified in patients in patients treated with extended-term DAPT (4.1% vs. 5.7%; aHR: 0.729; 95% CI: 0.543-0.980). The effect of DAPT&gt;12-month on the reduction of primary outcome was consistent across clinical presentations (stable CAD vs. ACS), P2Y 12 inhibitor (clopidogrel vs. ticagrelor), and LM bifurcation PCI (1- vs. 2-stent strategy). Conclusions: In a large cohort of consecutive patients undergoing LM PCI, longer DAPT duration (&gt;12 months) could achieve more favorable outcomes by reducing ischemic risk, not significantly offsetting the increases in clinically relevant bleeding events.

Evaluation of Optimal Dual Antiplatelet Therapy Duration for High-Risk Patients with Diabetes Following PCI

The efficacy and safety of prolonged (>1-year) dual antiplatelet therapy (DAPT) duration in high-risk patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) remain unknown. All patients undergoing PCI at Fuwai hospital between January 2013 and December 2013 were prospectively enrolled into the Fuwai PCI registry. A total of 3,696 high-risk diabetics patients with at least one additional atherothrombotic risk factor were screened for inclusion. The primary efficacy outcome was the composite of all-cause mortality, myocardial infarction, or stroke. The median follow-up duration was 887 days. 69.8% of DM patients were on DAPT at 1 year without discontinuation. Based on multivariate Cox regression model and inverse probability of treatment weighting (IPTW) analysis, long-term (>1-year) DAPT reduced the risk of primary efficacy outcome (1.7% vs 4.1%; adjusted hazard ratio [adjHR]: 0.382, 95% confidence interval [CI]: 0.252 to 0.577; IPTW-HR: 0.362 [0.241 to 0.542]), as well as cardiovascular death and definite/probable stent thrombosis, compared with short-course (≤ 1-year) DAPT. Risk of the safety end point of clinically relevant bleeding (adjHR: 0.920 [0.467 to 1.816]; IPTW-HR: 0.969 [0.486 to 1.932]) was comparable between longer DAPT and shorter DAPT. A lower number of net clinical benefit adverse outcomes was observed with >1year DAPT versus ≤ 1-year DAPT (adjHR: 0.471 [0.331 to 0.671]; IPTW-HR: 0.462 [0.327 to 0.652]), which appeared increasingly favorable in those with multiple atherothrombotic risk characteristics. In high-risk patients with DM receiving PCI who were event free at 1 year, DAPT prolongation resulted in significant reduction in the risk of ischemic events not offset by increase of clinically meaningful bleeding events, thereby achieving a net clinical benefit. Extending DAPT beyond the period mandated by guidelines seems reasonable in high-risk DM patients not deemed at high bleeding risk.

Impact of DAPT duration on clinical outcome after stent implantation for coronary bifurcation lesions: multicentre experience

Abstract Background The period of dual antiplatelet therapy (DAPT) following acute coronary syndrome (ACS) or stable coronary artery disease (SCAD) that is managed with coronary stenting is still under consideration. In real-world registries, the association between length of DAPT, bifurcation intervention and its effect on clinical outcome has been poorly studied. In sequential all-comer patients treated with stenting of coronary artery bifurcation lesions we examined the effect of DAPT length on clinical results including our single centre registry. Methods Responses were extracted from January 2017 to December 2018 on 536 consecutive patients who had PCI on coronary bifurcation at three centres in India. The primary endpoint of the analysis was the cumulative incidence of major adverse cardiac cerebrovascular events (MACCE), identified as a composite of cardiac death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR) and stroke during follow-up; the secondary objectives were the single occurrence of any of the aforementioned incidents. 496 patients (92.5 percent) had data on the length of DAPT. Group 1) DAPT&amp;lt;6-months (n=174); group 2) DAPT&amp;gt;6-months but &amp;lt;12-months (n=162); group 3) DAPT &amp;gt;12-months (n=160). Results In 490 (98.8 percent) patients with an 18-month median (CI: 12–28) follow-up was concluded. MACCE developed more often in the 18 Group 1 patients (10.3%) than in Group 2 and 3 versus 14 [8.6%] and 8 [5%], HR: 0.76, 95% CI: 0.67- 0.92, p&amp;lt;0.001), respectively. After correction for clinical and angiographic features this disparity persisted (HR: 0.68, 95% CI: 0.68–0.79, p&amp;lt;0.001). At Kaplan-Meier analysis, in patients who received DAPT with less than 6 months (p&amp;lt;0.001) the freedom from MACCE survival was substantially lower. Conclusions In a real-world registry of hospitalized patients with DES-PCI for coronary artery bifurcation stenosis, short DAPT length (&amp;lt;6 months) is correlated with a considerably higher risk of MACCE relative to longer DAPT. Funding Acknowledgement Type of funding sources: None.

COBRA PzF™ coronary stent in clinical and preclinical studies: setting the stage for new antithrombotic strategies?

Major advances have been made in coronary artery stent technology over the last decades. Drug-eluting stents reduced in-stent restenosis and have shown better outcomes compared with bare metal stents, yet some limitations still exist to their use. Because they delay healing of the vessel wall, longer dual antiplatelet therapy is mandatory to mitigate against stent thrombosis and this limitation is most concerning in subjects at high risk for bleeding. The COBRA PzF nanocoated coronary stent has been associated with accelerated endothelialization relative to drug-eluting stents, reduced inflammation and thromboresistance in preclinical studies, suggesting more flexible dual antiplatelet therapy requirement with potential benefits especially in those at high bleeding risk. Here, we discuss the significance of COBRA PzF in light of recent experimental and clinical studies.

P2Y12 Inhibitor Monotherapy Versus Conventional Dual Antiplatelet Therapy or Aspirin Monotherapy in Acute Coronary Syndrome: A Pooled Analysis of the SMART-DATE and SMART-CHOICE Trials

Controversy remains regarding the optimal antiplatelet regimen in patients with acute coronary syndrome (ACS). This study sought to investigate the efficacy and safety of P2Y12 inhibitor monotherapy compared with conventional dual antiplatelet therapy (DAPT) and aspirin monotherapy in patients with ACS undergoing percutaneous coronary intervention. Data on 4,453 patients were pooled from SMART-DATE and SMART-CHOICE randomized trials. Antiplatelet therapy regimens were categorized as P2Y12 inhibitor monotherapy (P2Y12 inhibitor monotherapy after 3-month DAPT), conventional DAPT (12-month or longer DAPT), and aspirin monotherapy (aspirin monotherapy after 6-month DAPT). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE, a composite of all-cause death, myocardial infarction, and stroke). Inverse-probability of treatment-weighted (IPTW) analysis was performed. At 1 year, patients in the P2Y12 inhibitor monotherapy had a comparable risk of MACCE compared with those in the conventional DAPT (IPTW-adjusted hazard ratio [HR], 0.655; 95% confidence interval [CI] 0.393 to 1.094; p = 0.106), and tended to have a lower risk of MACCE than those in the aspirin monotherapy (IPTW-adjusted HR, 0.606; 95% CI, 0.347 to 1.058; p = 0.078). The adjusted hazard for the Bleeding Academic Research Consortium (BARC) type 2 to 5 bleeding was significantly lower in P2Y12 inhibitor monotherapy than in conventional DAPT (IPTW-adjusted HR, 0.341; 95% CI, 0.190 to 0.614; p < 0.001) and in aspirin monotherapy (IPTW-adjusted HR, 0.359; 95% CI, 0.182 to 0.708; p = 0.003). In conclusion, among patients with ACS undergoing PCI, P2Y12 inhibitor monotherapy after 3-month DAPT reduced risk of bleeding compared with conventional DAPT and aspirin monotherapy after 6-month DAPT without increasing MACCE.

Influence of dual antiplatelet therapy duration on neointimal condition after second-generation drug-eluting stent implantation

Guidelines recommend shorter duration (1–12 months) for dual antiplatelet therapy (DAPT) in the second-generation drug-eluting stent (DES) era. However, whether shorter DAPT duration affects stent strut conditions and neointimal characteristics at mid-term follow-up remains uncertain. Therefore, we studied the relation between DAPT duration and vascular healing response as assessed by optical coherence tomography (OCT). This study was retrospective observational study. Participants comprised 64 patients who underwent serial OCT at both 9 and 18 months after DES implantation. All patients received DAPT until the 9-month follow-up then were divided into two groups: 49 patients who continued DAPT (longer DAPT group); and 15 patients who stopped taking the P2Y12 inhibitor and were treated with aspirin alone (shorter DAPT group) at the 18-month follow-up. Using OCT, we evaluated and compared stent strut conditions and neointimal characteristics between groups at both 9 and 18 months after stent implantation. Baseline clinical and procedural parameters were mostly similar between groups. At the 18-month follow-up, no in-stent thrombus assessed by OCT was observed in either group. No significant differences in OCT characteristics or measurements of neointima were seen between groups at 9- or 18-month follow-ups. Neointimal volume increased from 9 to 18 months in both groups, with a similar degree of neointimal proliferation in both groups (shorter DAPT group, 0.23 ± 0.29 mm3/mm; longer DAPT group, 0.19 ± 0.27 mm3/mm; P = 0.56). In conclusion, interrupting DAPT 9 months after second-generation DES implantation did not affect the development of in-stent thrombus, neointimal proliferation or stent strut coverage at 18-month follow-up compared with continuing DAPT.

Benefits and Risks of Prolonged Duration Dual Antiplatelet Therapy (Clopidogrel and Aspirin) After Percutaneous Coronary Intervention in High-Risk Patients With Diabetes Mellitus

The efficacy and safety of prolonged (>1-year) dual antiplatelet therapy (DAPT) duration in high-risk patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) remain unknown. All patients undergoing PCI at Fuwai hospital between January 2013 and December 2013 were prospectively enrolled into the Fuwai PCI registry. A total of 3,696 high-risk diabetics patients with at least one additional atherothrombotic risk factor were screened for inclusion. The primary efficacy outcome was the composite of all-cause mortality, myocardial infarction, or stroke. The median follow-up duration was 887 days. 69.8% of DM patients were on DAPT at 1 year without discontinuation. Based on multivariate Cox regression model and inverse probability of treatment weighting (IPTW) analysis, long-term (>1-year) DAPT reduced the risk of primary efficacy outcome (1.7% vs 4.1%; adjusted hazard ratio [adjHR]: 0.382, 95% confidence interval [CI]: 0.252 to 0.577; IPTW-HR: 0.362 [0.241 to 0.542]), as well as cardiovascular death and definite/probable stent thrombosis, compared with short-course (≤1-year) DAPT. Risk of the safety end point of clinically relevant bleeding (adjHR: 0.920 [0.467 to 1.816]; IPTW-HR: 0.969 [0.486 to 1.932]) was comparable between longer DAPT and shorter DAPT. A lower number of net clinical benefit adverse outcomes was observed with >1-year DAPT versus ≤1-year DAPT (adjHR: 0.471 [0.331 to 0.671]; IPTW-HR: 0.462 [0.327 to 0.652]), which appeared increasingly favorable in those with multiple atherothrombotic risk characteristics. In high-risk patients with DM receiving PCI who were event free at 1 year, DAPT prolongation resulted in significant reduction in the risk of ischemic events not offset by increase of clinically meaningful bleeding events, thereby achieving a net clinical benefit. Extending DAPT beyond the period mandated by guidelines seems reasonable in high-risk DM patients not deemed at high bleeding risk.

Accuracy of the PARIS score and PCI complexity to predict ischemic events in patients treated with very thin stents in unprotected left main or coronary bifurcations.

The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed. The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents. After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI. In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

P2794Real-world reasons and outcomes for 1-month versus longer dual antiplatelet therapy strategies with a polymer-free biolimus A9-coated stent: insights from the all-comers FREEDOM registry

Abstract Background The LEADERS FREE trial established the favourable clinical profile of a new polymer-free biolimus A9-eluting stent (PF-BES) in patients at high bleeding risk when used with a 1-month dual anti-platelet therapy (DAPT) strategy. Purpose This is the first study evaluating real-world reasons and outcomes for a 1-month versus longer DAPT strategies following PF-BES percutaneous coronary intervention (PCI). Methods FREEDOM is an all-comers registry including all patients who underwent PCI with at least one PF-BES at 10 sites, between January 2016 and July 2018. Patients were stratified according to DAPT strategy at discharge (1-month vs &gt;1-month). Baseline features, reasons for PF-BES as reported by the treating physician, and outcomes were compared between groups. Primary outcomes were the 390-day estimates of a patient-oriented composite endpoint (POCE: death, myocardial infarction (MI) or target vessel revascularization) and of a device-oriented composite endpoint (DOCE: cardiac death, target vessel-MI or ischemia-driven target lesion revascularization). Incidence rates were adjusted for clinically relevant factors and outcome predictors. To avoid survival bias, landmark analyses starting from 1-month post-PCI were further carried. Results Following PF-BES PCI, 328 (40.3%) patients were discharged with 1-month DAPT and 485 (59.6%) patients with longer DAPT (median 12 months, IQR 6–12 months). Patients with hypertension or on oral anticoagulation (OAT) were more likely and patients with a previous or an index MI were less likely to be discharged on 1-month DAPT. Patients prescribed with 1-month DAPT were more likely to have had a PF-BES for a LEADERS FREE high bleeding risk criterium than those with longer DAPT (90.2% vs 69.9%, p=0.001). The same association was observed when the reason for PF-BES was a planned major surgery (13.1% vs 6.2%; p=0.001) or OAC to be continued after PCI (38.7% vs 16.5%, p&lt;0.001). Conversely, patients with planned longer DAPT were more likely to have had a PF-BES following the operator preference (2.4% vs 15.5%, p&lt;0.001) or for a reason other than a LEADERS FREE criterium or operator preference (5.2% vs 11.3%, p&lt;0.001). No between-groups differences in the occurrence of the primary outcomes (1-month vs &gt;1-month DAPT: POCE 11.9% vs 13.2%, p=0.747; adj-HR 1.29 [95% CI 0.78–2.10]; DOCE: 4.8% vs 8.1%, p=0.500; adj-HR 1.01 [95% CI 0.50–2.07]) and of bleedings (any: 11.3% vs 9.4%, p=0.472; adj-HR 0.87 [95% CI 0.51–1-50]; BARC 3–5: 4.2% vs 2.2%; p=0.108; adj-HR 1.50 [95% CI 0.58–3.87]) were observed. Landmark analyses showed similar results. Conclusions In a large contemporary all-comers registry, factors reflecting the operator-perceived patient high bleeding risk were the main drivers of a very-short DAPT strategy following PF-BES PCI. We found no interaction of DAPT duration with outcomes following PF-BES PCI, an observation warranting investigation in adequately powered randomised studies.

TCT-394 Differential Effects of Prolonged Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients Presenting With Versus Without Acute Myocardial Infarction

Despite the broad spectrum of acute coronary syndrome, the benefits and risks of prolonged dual antiplatelet therapy (DAPT) according to initial presentation with or without myocardial infarction (MI) have not been well studied. In the SMART-DATE trial, 12-month or longer DAPT, when compared with 6

Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry.

Limited data are available concerning differences in clinical outcomes for real-life patients treated with ticagrelor versus prasugrel after percutaneous coronary intervention (PCI). Our objective was to determine and compare the efficacy and safety of ticagrelor and prasugrel in a real-world population. RENAMI was a retrospective, observational registry including the data and outcomes of consecutive patients with acute coronary syndrome (ACS) who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT) between January 2012 and January 2016. The mean follow-up period was 17 ± 9months. In total, 11 university hospitals from six European countries participated. After propensity-score matching, there were no substantial differences in the baseline clinical and interventional features. All patients were treated with acetylsalicylic acid plus prasugrel 10mg once daily or acetylsalicylic acid plus ticagrelor 90mg twice daily. Mean duration of DAPT was 12.04 ± 3.4months with prasugrel and 11.90 ± 4.1months with ticagrelor (p = 0.47). The primary and secondary endpoints were long-term net adverse clinical events (NACE) and major adverse cardiovascular events (MACE), respectively, along with their single components. Subgroup analysis for freedom from NACE and MACE was performed according to length of DAPT and clinical presentation [ST-elevation myocardial infarction (STEMI)-ACS versus non-ST-elevation myocardial infarction (NSTEMI)-ACS]. In total, 4424 patients (2725 ticagrelor, 1699 prasugrel) were enrolled. After propensity-score matching, 1290 patients in each cohort were included in the analysis. At 12months, the incidence of both NACE and MACE was lower with prasugrel (NACE: 5.3% vs. 8.5% [p=0.001]; MACE: 5% vs. 8.1% [p= 0.001]) mainly driven by a reduction in recurrent myocardial infarction (MI) (2.4 vs. 4.0%; p = 0.029) and a lower rate of Bleeding Academic Research Consortium (BARC) 3-5 bleeding (1.5 vs. 2.9%; p = 0.011). The benefit of prasugrel was confirmed for patients with NSTEMI and for those discharged with a DAPT regimen of ≤ 12months. Only a trend in the reduction of NACE and MACE was noted for STEMI or for those treated with longer DAPT. Comparison of these drugs suggested that prasugrel is safer and more efficacious than ticagrelor in combination with aspirin after NSTEMI but not STEMI. No differences were found for events occurring after 12months. The nonrandomized design of the present research means further studies are required to support these findings.

Risk-Benefit Profile of Longer-Than-1-Year Dual-Antiplatelet Therapy Duration After Drug-Eluting Stent Implantation in Relation to Clinical Presentation.

We sought to determine whether the risks and benefits of prolonging dual-antiplatelet therapy (DAPT) beyond 1 year after drug-eluting stent implantation depend on clinical presentation in a meta-analysis of randomized controlled trials. Randomized controlled trials comparing ≤1- versus >1-year DAPT after drug-eluting stent placement were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. The primary efficacy end point was myocardial infarction, whereas the primary safety end point was major bleeding. Net clinical benefit was defined as the composite of myocardial infarction or major bleeding. Outcomes were analyzed according to patient presentation with stable ischemic heart disease versus acute coronary syndromes. The meta-analysis included 6 trials with a total of 21 457 patients, including 14 132 with stable ischemic heart disease and 7325 with acute coronary syndrome. After a median follow-up of 19.5 months, ≤1-year DAPT was associated with higher rates of myocardial infarction compared with >1-year DAPT (hazard ratio [HR], 1.63; 95% CI, 1.37-1.95), with no interaction apparent between treatment effect and clinical presentation. Shorter DAPT was associated with reduced rates of major bleeding compared with longer DAPT (HR, 0.64; 95% CI, 0.42-0.99) with no significant interaction between treatment effect and clinical presentation. However, a net clinical benefit of >1-year DAPT was present in patients with acute coronary syndrome (HR of shorter versus longer DAPT, 1.59; 95% CI, 1.24-2.02) but not in those with stable ischemic heart disease (HR, 1.15; 95% CI, 0.89-1.51; Pinteraction=0.04). Shorter DAPT was also associated with lower rates of noncardiac mortality compared with longer DAPT (HR, 0.71; 95% CI, 0.52-0.96), with no significant interaction between treatment effect and clinical presentation ( Pinteraction=0.12). Compared with ≤1-year DAPT, >1-year DAPT reduces the risk of myocardial infarction but increases the risk of major bleeding and noncardiac mortality. A net clinical benefit of extended DAPT was apparent for patients with acute coronary syndrome but not for those with stable ischemic heart disease.

LONG-TERM OUTCOME COMPARISON OF DRUG-ELUTING STENTS AND BARE-METAL STENTS IN PATIENTS WITH HIGH BLEEDING RISK

There has been an increased use of drug-eluting stents (DES) for percutaneous coronary intervention (PCI). It was considered that patients with DES needed longer dual anti-platelet therapy (DAPT) than those with bare-metal stents (BMS) to prevent stent thrombosis. Although longer DAPT duration may

Clopidogrel and aspirin after ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis of randomized clinical trials.

Recurrent stroke is common immediately following a transient ischemic attack (TIA) or ischemic stroke. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin may provide greater protection against subsequent stroke than monotherapy. Electronic databases were searched for randomized clinical trials (RCTs) comparing DAPT with monotherapy in ischemic stroke/TIA. Sixteen RCTs with a total of 29,032 patients were included. Compared with monotherapy, DAPT was associated with significantly lower rates of any stroke (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.72-0.89) and ischemic stroke (RR 0.75; 95% CI 0.66-0.85) during any follow-up period. Although significant increases in intracranial bleeding (RR 1.55; 95% CI 1.20-2.01) and major bleeding (RR 1.90; 95% CI 1.33-2.72) were associated with DAPT, especially with long-term follow-up, the number needed to harm was 258 and 113, respectively. Nevertheless, short-duration DAPT (≤ 1month) started during the early acute ischemic phase was associated with less bleeding than longer DAPT and greater reduction of recurrent strokes compared with monotherapy. In contrast, long DAPT and DAPT started later after the index event (≥ 1month) were associated with similar rates of any stroke and increased risks of bleeding compared with monotherapy. Other clinical outcomes were essentially similar between the two groups and included recurrent TIA (RR 0.88; 95%CI 0.72-1.07), myocardial infarction (RR 1.04; 95% CI 0.84-1.29), vascular death (RR 0.99; 95%CI 0.82-1.19), and any death (RR 1.12; 95% CI 0.88-1.42). Similar findings were observed in patients who presented with minor stroke/TIA. Conclusions: Among patients who presented with ischemic stroke/TIA, short-course clopidogrel plus aspirin immediately following the index event appears to be more effective than and as safe as monotherapy for secondary stroke prevention.

Are Shorter Durations of Dual Antiplatelet Therapy Acceptable Following Percutaneous Coronary Intervention?

Much debate has centered on whether or not the standard 12-month duration of dual antiplatelet therapy (DAPT) is still necessary postpercutaneous coronary intervention, given recent improvements in stent technology. The benefits of shorter (3-6 months) durations of DAPT include a potential lower risk for bleeding and less patient drug cost and pill burden. Although randomized clinical trials have shown noninferiority for shorter versus longer DAPT regimens in many regards, some endpoints (e.g., myocardial infarction) may still occur less frequently with longer DAPT regimens, particularly in higher risk populations (e.g., acute coronary syndromes). Bleeding risk is either comparable or less with shorter versus longer DAPT regimens. Given the lack of unequivocal data regarding the equality of shorter versus longer DAPT regimens in all patients, there is a growing consensus that an individualized approach is advisable for determining DAPT duration postpercutaneous coronary intervention. Clinical decision aids and updated clinical practice guidelines are available that consider risk:benefit ratios and clinical trial data to assist the clinician in developing a personalized DAPT regimen.

Relevance of Antiplatelet Therapy Duration After Stent-Assisted Coil Embolization for Unruptured Intracranial Aneurysms

The optimal duration of dual-antiplatelet therapy (DAPT) for preventing delayed thromboembolic events (DTEs) remains unclear. We aimed to determine whether longer DAPT provides improved protection against delayed DTEs. This retrospective cohort study included 507 stent-assisted coil embolization procedures using a single stent for unruptured intracranial aneurysms. We performed coarsened exact matching according to the duration of maintenance DAPT. DTEs were defined as any neurologic symptoms concerning the stented vascular territory and occurring at 1 month or later after the procedure. After stratification according to DAPT duration (short-term, <9 months; long-term, ≥9 months), the log-rank test and Z-analysis were performed to evaluate the efficacy of long-term DAPT for preventing DTEs. Of 507 treated patients (median follow-up, 44 months), 25 (4.9%) experienced DTEs at 1 month after the procedure. Among all DTEs, 9 (1.8%) were infarctions confirmed on magnetic resonance imaging. Permanent neurologic deficit (modified Rankin Scale score ≥2) occurred in 2 (0.4%) patients. On procedure-to-event analysis, long-term DAPT was not superior for preventing DTEs. Most events occurred within 1 month of switching from DAPT to single-antiplatelet therapy, regardless of DAPT duration. The longest time from the procedure to DTE occurrence was 22 months. Age older than 54.5 years was identified as independent risk factor for DTE-stroke. Compared with short-term DAPT, long-term DAPT delays the occurrence of DTEs but does not lower their incidence. Longer-term DAPT (>9 months) should be considered after stent-assisted coil embolization for unruptured intracranial aneurysms, although its efficacy remains to be clarified.

6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial

Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population. We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2-5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453. Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6%] patients vs 39 [2·9%]; hazard ratio [HR] 0·90 [95% CI 0·57-1·42]; p=0·90) and neither did stroke (11 [0·8%] patients vs 12 [0·9%]; 0·92 [0·41-2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%] patients vs ten [0·8%]; 2·41 [1·15-5·05]; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 [95% CI 0·68-3·35]; p=0·32). The rate of BARC type 2-5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95% CI 0·45-1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis. The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care. Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.

6- Versus 24-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents in Patients Nonresistant to Aspirin: Final Results of the ITALIC Trial (Is There a Life for DES After Discontinuation of Clopidogrel)

ObjectivesThe aim of this study was to test the hypothesis that 6-month dual antiplatelet therapy (DAPT) is noninferior to 24-month DAPT in aspirin-sensitive patients. BackgroundThe ITALIC (Is There a Life for DES After Discontinuation of Clopidogrel) trial showed that rates of bleeding and thrombotic events at 1 year were much the same with 6 versus 12 months of DAPT after percutaneous coronary intervention with second-generation drug-eluting stents. In this report, 2-year follow-up is presented. MethodsIn a multicenter randomized study, patients with confirmed nonresistance to aspirin undergoing drug-eluting stent implantation were allocated to 6 or 24 months of DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post–percutaneous coronary intervention. The secondary endpoints comprised the same composite endpoint at 24 months and each individual component. ResultsOverall, 2,031 patients from 70 centers were screened; 926 were randomized to 6-month and 924 to 24-month DAPT. Noninferiority was demonstrated for 6- versus 12-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: −1.04% to 1.26%; p = 0.0002). At 2 years, the composite endpoint was unchanged, at 3.5% for 6 months and 3.7% for 24 months (p = 0.79), and rates of myocardial infarction (1.3% vs. 1.0%; p = 0.51), stroke (0.6% vs. 0.8%; p = 0.77), and target vessel revascularization (1.0% vs. 0.3%; p = 0.09) were likewise similar. There was a trend toward higher mortality with longer DAPT (2.2% vs. 1.2%; p = 0.11). Four patients (0.4%) in the 24-month group and none in the 6-month group had major bleeding. ConclusionsTwo-year outcomes in the ITALIC trial confirmed the 1-year results and showed that patients receiving 6-month DAPT after percutaneous coronary intervention with second-generation drug-eluting stent have similar outcomes to those receiving 24-month DAPT.