Impact of complete revascularization in the IschemiaTrial

BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

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

AIM: We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation.METHODS AND RESULTS: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.

Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting

BACKGROUND:Although some randomized controlled trials (RCTs) and meta-analyses have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated with increased mortality, the mechanistic underpinnings of this association remain unclear.OBJECTIVES:The aim of this study was to analyze the associations among bleeding, mortality, and DAPT duration after drug-eluting stent implantation in a meta-analysis of RCTs.METHODS:RCTs comparing different DAPT durations after drug-eluting stent placement were sought through the MEDLINE, Embase, and Cochrane databases and the proceedings of international meetings. Deaths were considered possibly bleeding related if occurring within 1 year of the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary analysis was performed in a modified intention-to-treat population in which events occurring when all patients were on DAPT were excluded.

A novel drug-coated scoring balloon for the treatment of coronary in-stent restenosis: Results from the multi-center randomized controlled PATENT-C first in human trial

Scoring balloons produce excellent acute results in the treatment of instentrestenosis (ISR), fibro-calcific and bifurcation lesions but have not been shown toaffect the restenosis rate. A novel paclitaxel-coated scoring balloon (SB) was developedand tested to overcome this limitation. Methods and Results: SB were coatedwith paclitaxel admixed with a specific excipient. Patients at four clinical sites inGermany and one in Brazil with ISR of coronary bare metal stent (BMS) were randomized1:1 to treatment with either a drug-coated or uncoated SB. Baseline and 6-monthfollow-up quantitative coronary angiography was performed by an independent blindedcore lab and all patients will be evaluated clinically for up to one year. The primaryendpoint was angiographic in-segment late lumen loss (LLL). Secondary endpoints included the rate of clinically driven target lesion revascularization (TLR), composite ofmajor adverse cardiovascular events (MACE), stent thrombosis and other variables.Sixty-one patients were randomized (28 uncoated and 33 drug-coated SB); mean age65 years, males 72%, and presence of diabetes 39%. At 6-month angiography, insegmentLLL was 0.48 6 0.51 mm in the uncoated SB group versus 0.17 6 0.40 mm inthe drug-coated SB group (P 5 0.01; ITT analysis). The rate of binary restenosis was41% in the uncoated SB group versus 7% in the drug-coated SB group (P 5 0.004). TheMACE rate was 32% with the uncoated SB vs. 6% in the drug-coated SB group(P 5 0.016). This difference was primarily due to the reduced need for clinically drivenTLR in the coated SB group (3% vs. 32% P 5 0.004). Conclusions: A novel paclitaxelcoatedcoronary SB has been developed and successfully used in a first-in-human randomized controlled trial...

Efficacy and safety of dual antiplatelet therapy after complex PCI

BACKGROUND: Optimal upfront dual antiplatelet therapy (DAPT) duration after complex percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear. OBJECTIVES: This study investigated the efficacy and safety of long-term (≥12 months) versus short-term (3 or 6 months) DAPT with aspirin and clopidogrel according to PCI complexity. METHODS: The authors pooled patient-level data from 6 randomized controlled trials investigating DAPT durations after PCI. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. The primary safety endpoint was major bleeding. Intention-to-treat was the primary analytic approach. RESULTS: Of 9,577 patients included in the pooled dataset for whom procedural variables were available, 1,680 (17.5%) underwent complex PCI. Overall, 85% of patients received new-generation DES. At a median follow-up time of 392 days (interquartile range: 366 to 710 days), patients who underwent complex PCI had a higher risk of MACE (adjusted hazard ratio [HR]: 1.98; 95% confidence interval [CI]: 1.50 to 2.60; p < 0.0001)...

Short- Versus Long-TermDual Antiplatelet Therapy AfterDrug-Eluting Stent Implantation

Randomized controlled trials comparing short- (#6 months) with long-term ($1 year) dual antiplatelettherapy (DAPT) after drug-eluting stent(s) (DES) placement have been insufficiently powered to detect significantdifferences in the risk of major adverse cardiac events (MACE).OBJECTIVES This study sought to compare clinical outcomes between short- (#6 months) and long-term (1 year)DAPT and among 3 months, 6 months, and 1 year of DAPT post-DES placement by performing an individual patient datapairwise and network meta-analysis.METHODS Randomized controlled trials comparing DAPT durations after DES placement were searched through theMEDLINE, EMBASE, and Cochrane databases and in international meeting proceedings. The primary study outcomewas 1-year risk of MACE (cardiac death, myocardial infarction, or definite/probable stent thrombosis).RESULTS Four trials including 8,180 randomized patients were identified. At 1-year follow-up, short-term DAPT wasassociated with similar rates of MACE (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.86 to 1.43; p » 0.44), butsignificantly lower rates of bleeding (HR: 0.66; 95% CI: 0.46 to 0.94; p » 0.03) versus prolonged DAPT. Comparableresults were apparent in the landmark period between DAPT discontinuation and 1-year follow-up (for MACE: HR: 1.20;95% CI: 0.77 to 1.89; p » 0.42) (for bleeding: HR: 0.44; 95% CI: 0.21 to 0.91; p » 0.03). There were no significantdifferences in 1-year rates of MACE among 3-month versus 1-year DAPT, 6-month versus 1-year DAPT, or 3-month versus6-month DAPT.CONCLUSIONS Compared with prolonged DAPT, short-term DAPT is associated with similar rates of MACE but lowerrates of bleeding after DES placement.

Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials

BACKGROUND:Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies.METHODS:We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches.FINDINGS:We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31,666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year...