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The authors comment on a Japanese study that examined iterations of shorter-duration dual antiplatelet therapy (DAPT) in patients in Japan who received everolimus-eluting stents by discontinuing aspirin instead of the P2Y12 inhibitor as has commonly been the approach. They compare the findings of the study with those of a similar study in Korea that involved patients who received a current-generation drug-eluting stent. They also discuss the possible impact of the results on clinical practice.

Objectives: This study sought to evaluate ischemic and bleeding outcomes in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Background: Previous studies have shown that CKD is associated with poor outcomes after PCI. However, these studies were largely conducted before the introduction of DES and aggressive antithrombotic therapy or were performed in the setting of randomized trials. With data from a contemporary registry, we evaluated the influence of CKD on major cardiovascular events and bleeding complications in unselected “real-world” patients undergoing PCI. Methods: Data from 4,791 patients enrolled in the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) Registry between July 2004 and September 2005 were analyzed. Patients were stratified into 4 groups: creatinine clearance (CrCl) >75, 50 to 75, 30 to 49 and <30 ml/min. Results: During the index hospital stay, there was a step-wise increase in bleeding complications with decreasing CrCl (3.3%, 5.0%, 8.8%, and 14.3%; p < 0.0001 for trend). Lower CrCl was also associated with more frequent death or myocardial infarction (MI) during the initial hospital stay (p = 0.001) and at 1 year (p < 0.001). These findings were confirmed in multivariate analyses that adjusted for baseline differences in demographic, clinical, and angiographic factors. Use of guideline-recommended medications at 1 year, including aspirin, clopidogrel, angiotensin-converting enzyme inhibitors, and statins, also decreased with declining renal function. Conclusions: Renal function is an independent and powerful predictor of bleeding and ischemic complications in the era of DES and contemporary antithrombotic therapy in patients undergoing PCI. The low use of guideline-recommended drugs among patients with CKD undergoing PCI might contribute to these adverse outcomes and warrants further evaluation. [Copyright &y& Elsevier]

SUMMARY BACKGROUND: Two placebo-controlled trials testing intravenous platelet glycoprotein IIb/IIIa antagonists in the setting of percutaneous coronary revascularisation with intracoronary stents have shown a durable reduction in ischaemic events to 6 months. These trials differed regarding their patient population, IIb/IIIa inhibitor, and reported extent of benefit. Whether a small-molecule agent affecting only the IIb/IIIa receptor would provide a similar outcome for ischaemic events and clinical restenosis at 6 months when directly compared with a monoclonal antibody known to affect several integrin receptors is unknown. METHODS: In 18 countries at 149 hospitals, 4809 patients undergoing elective or urgent stent implantation were randomly assigned a bolus and infusion of tirofiban or abciximab. Patients were followed for 6 months for the occurrence of death, myocardial infarction, and any target-vessel revascularisation. The results at 30 days have been reported previously. FINDINGS: At 6 months the composite endpoint of death, myocardial infarction, and target-vessel revascularisation occurred in 356 (14.8%) patients who received tirofiban and 345 (14.3%) patients who received abciximab (hazard ratio 1.04, 95% CI 0.90-1.21; p=0.591). The rates for the individual endpoints were 191 (8.0%) versus 159 (6.6%) for myocardial infarction (hazard ratio 1.21, 95% CI 0.98-1.50; p=0.074), 26 (1.1%) versus 25 (1.0%) for death (1.04, 0.60-1.80; p=0.893), and 194 (8.1%) versus 208 (8.6%) for target-vessel revascularisation (0.93, 0.77-1.14; p=0.495). INTERPRETATION: At 6 months, tirofiban provided a similar level of overall protection to abciximab against the composite of death, myocardial infarction, and any target-vessel revascularisation. [ABSTRACT FROM AUTHOR]

The editorial focuses on target vessel revascularization (TVR) and in-stent restenosis (ISR). The results of clinical trials, such as TAXUS V ISR whose patients had paclitaxel-eluting stents and Sirolimus-Eluting Stent with Vascular Brachytherapy for the Treatment of In-Stent Restonisis (SISR), indicate outcomes from drug-eluting stent implantation are better than those using brachytherapy. The author suggests methods for further research.

This editorial comments on a study in this issue which compared two drug-eluting stents and found little difference in their efficacy. Although the study did not find much difference, the authors say a meta-analysis of 38 trials suggested that the sirolimus-eluting stents were better than the paclitaxel-eluting stents. Physicians will have to choose which stent to use based on multiple factors such as safety, availability, cost and effectiveness.

A response by David J. Moliterno to a letter to the editor about his article related to drug-eluting coronary stents in a previous issue is presented.

The article presents the author's opinion on the effectiveness of the placement of a coronary-artery stent that has emerged as the technique of choice for percutaneous coronary intervention restenosis. According to the author, the technique provides a substantial reduction in the percentage of patients who need subsequent target-lesion revascularization. Several clinical cases are also mentioned in the article.

Background: The Bleeding Academic Research Consortium (BARC) scale has been proposed to standardize bleeding endpoint definitions and reporting in cardiovascular trials. Validation in large cohorts of patients is needed.Objectives: This study sought to investigate the relationship between BARC-classified bleeding and mortality and compared its prognostic value against 2 validated bleeding scales: TIMI (Thrombolysis In Myocardial Infarction) and GUSTO (Global Use of Strategies to Open Occluded Arteries).Methods: We analyzed bleeding in 12,944 patients with acute coronary syndromes without ST-segment elevation, with or without early invasive strategy. The main outcome measure was all-cause death.Results: During follow-up (median: 502 days), noncoronary artery bypass graft (CABG) bleeding occurred in 1,998 (15.4%) patients according to BARC (grades 2, 3, or 5), 484 (3.7%) patients according to TIMI minor/major, and 514 (4.0%) patients according to GUSTO moderate/severe criteria. CABG-related bleeding (BARC 4) occurred in 155 (1.2%) patients. Patients with BARC (2, 3, or 4) bleeding had a significant increase in risk of death versus patients without bleeding (BARC 0 or 1); the hazard was highest in the 30 days after bleeding (hazard ratio: 7.35; 95% confidence interval: 5.59 to 9.68; p < 0.0001) and remained significant up to 1 year. The hazard of mortality increased progressively with non-CABG BARC grades. BARC 4 bleeds were significantly associated with mortality within 30 days (hazard ratio: 10.05; 95% confidence interval: 5.41 to 18.69; p < 0.0001), but not thereafter. Inclusion of BARC (2, 3, or 4) bleeding in the 1-year mortality model with baseline characteristics improved it to an extent comparable to TIMI minor/major and GUSTO moderate/severe bleeding.Conclusions: In patients with acute coronary syndromes without ST-segment elevation, bleeding assessed with the BARC scale was significantly associated with risk of subsequent death up to 1 year after the event and risk of mortality increased gradually with higher BARC grades. Our results support adoption of the BARC bleeding scale in ACS clinical trials. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER] [Study P04736]; NCT00527943). [ABSTRACT FROM AUTHOR]

The therapeutic potential of vorapaxar in patients with none--ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (PCI) is unknown. This prespecified analysis of a postrandomization subgroup evaluated the effects of vorapaxar compared with placebo among Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) participants undergoing PCI, focusing on the implanted stent type (drug-eluting stent [DES] vs bare-metal stent [BMS]). Among 12,944 recruited patients, 7,479 (57.8%) underwent PCI during index hospitalization, and 3,060 (40.9%) of those patients received exclusively BMS, whereas 4,015 (53.7%) received DES. The median (twenty-fifth, seventy-fifth percentiles) duration of thienopyridine therapy was 133 days (47, 246) with BMS and 221 days (88, 341) with DES. At 2 years among patients undergoing PCI, the primary (cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) and secondary (cardiovascular death, myocardial infarction, or stroke) end points did not differ between vorapaxar and placebo groups, which was consistent with the treatment effect observed in the overall study population (p value for interaction [ 0.540). However, the treatment effect trended greater (p value for interaction[0.069) and the risk for bleeding in patients taking vorapaxar versus placebo appeared attenuated in BMS-only recipients. After adjustment for confounders, the interaction was no longer significant (p value[ 0.301). The covariate that mostly explained the stent-type-by-treatment interaction was the duration of clopidogrel therapy. In conclusion, among patients with PCI, the effect of vorapaxar is consistent with the overall TRACER results. Patients who received a BMS underwent shorter courses of clopidogrel therapy and displayed trends toward greater ischemic benefit from vorapaxar and lesser bleeding risk, compared with patients who received a DES. [ABSTRACT FROM AUTHOR]

Intense investigation continues on the pathobiology of stent thrombosis (ST) because of its morbidity and mortality. Because little advance has been made in outcomes following ST, ongoing research is focused on further understanding predictive factors as well as ST frequency and timing in various patient subsets, depending upon whether a drug-eluting stent or bare-metal stent has been implanted. Although the preventive role of antiplatelet therapies remains unchallenged, new data on genomics and variability in response to antiplatelet therapy, as well as the effects of novel therapeutic agents and duration of therapy, have become available. The goal remains identification of patients at particularly increased risk of ST so that optimal prevention strategies can be developed and employed. [ABSTRACT FROM AUTHOR]

Abstract: Dual antiplatelet therapy with aspirin and a thienopyridine has been shown to reduce cardiac events after coronary stenting. However, many patients and healthcare providers prematurely discontinue dual antiplatelet therapy, which greatly increases the risk of stent thrombosis, myocardial infarction, and death. This advisory stresses the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent and educating the patient and healthcare providers about hazards of premature discontinuation. It also recommends postponing elective surgery for 1 year, and if surgery cannot be deferred, considering the continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents. [Copyright &y& Elsevier]

Clinical outcomes after multivessel versus single-vessel percutaneous coronary intervention (PCI) in the era of stents, glycoprotein IIb/IIIa inhibitors, and clopidogrel pretreatment have not been well studied. Thus, we compared outcomes from the Do Tirofiban and ReoPro Give Similar Efficacy Outcome Trial (TARGET) for patients who underwent multivessel versus single-vessel PCI and separately considered the effect of acute coronary syndromes on the results. Composite clinical outcomes (death, myocardial infarction, and target vessel revascularization) were evaluated at 30 days and 6 months and mortality at 1 year. Safety analysis included in-patient major and minor bleeding. Despite similar baseline characteristics, patients who underwent multivessel PCI (n = 775) had significantly higher 30-day and 6-month composite event rates than did those who were treated in a single coronary artery territory (n = 3,969). This association remained significant at 30 days (hazard ratio 1.57, 95% confidence interval 1.06 to 2.33, p = 0.025) after using propensity matching to minimize confounding factors. The higher event rate was primarily due to an increase in periprocedural myocardial infarction. However, there were no significant differences in propensity-matched ischemic outcomes at 6 months and 1 year or in bleeding. In addition, in a propensity-matched analysis that included 810 patients with acute coronary syndrome, multivessel stenting resulted in numerically more ischemic events than did single-vessel stenting, although this did not reach statistical significance (hazard ratio 1.32, 95% confidence interval 0.85 to 2.05, p = 0.221). In conclusion, multivessel PCI was more often associated with periprocedural myocardial infarction than single-vessel intervention, although this did not translate into higher 1-year mortality. A randomized trial comparing multivessel PCI with staged or surgical revascularization is warranted. [Copyright &y& Elsevier]

We studied stent thrombosis in 4,607 patients with acute coronary syndromes who received a coronary stent as part of routine care during 2 trials of aspirin versus sibrafiban for secondary prevention. In these patients, stent thrombosis occurred more often than in previous patients who underwent elective percutaneous coronary intervention. These patients and their outcomes may be more representative of patients with typical acute coronary syndromes undergoing stenting in clinical practice. [Copyright &y& Elsevier]

The association between peripheral vascular disease and outcomes after percutaneous coronary intervention was examined in the Do Tirofiban and Reopro Give Similar Efficacy Outcome Trial (TARGET). After adjustments in a multivariate model, a history of peripheral vascular disease was found to be associated with a two- to threefold increase in mortality at 1 year after coronary stent placement. [Copyright &y& Elsevier]