Entrapment of dissection flap and intimal tissue cleavage during rotational atherectomy

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The Impact of the Second Generation Everolimus-eluting Stent in Daily Clinical Practice

Clinical studies with first-generation sirolimus-eluting stents (SES) and paclitaxel- eluting stents (PES) have demonstrate a dramatic reduction in restenosis rates compared with bare-metal stents (BMS)1,2, however, reintervention rates were still high in patients with complex coronary artery disease3, and an ongoing propensity for stent thrombosis (ST) beyond one year raised further concerns regarding safety issues with these devices4. Furthermore, as both of these devices were relatively high-profile stainless steel stents, they were difficult to deliver in complex anatomy, and the SES in particular was prone to a high fracture rate, contributing to late adverse events. The everolimus-eluting stent (EES), (XIENCE V, Abbott Vascular, CA, USA; also distributed as the PROMUS stent by Boston Scientific, MA, USA) is a secondgeneration drug-eluting stent (DES) designed to overcome the limitations of earlier DES

Factors associated with deferred lesion failure following fractional flow reserve assessment in patients with diabetes mellitus

Objective: To explore the predictors of deferred lesion failure (DLF) in patients with diabetes mellitus (DM) and lesions with a fractional flow reserve (FFR) >0.80 and to examine whether a predictive relationship between negative FFR values (>0.80\u20131.00) and DLF exists. Background: DM is associated with rapidly progressive atherosclerosis and predictors of DLF in FFR negative lesions in this high-risk group are unknown. Methods: All DM patients who underwent FFR-assessment between 1/01/2010 and 31/12/2013 were included, and followed until 1/7/2015. Patients carrying 651 FFR negative lesion(s) were assessed for DLF, and multivariate models used to identify independent factors associated with DLF. Results: A total of 205 patients with 252 FFR >0.80 lesions were identified. At a mean follow-up of 3.1 \ub1 1.4 years, DLF occurred in 29/205 (14.1%) patients, 31/252 (12.3%) lesions. Using marginal Cox regression multivariate analysis, insulin requiring DM [HR 2.24 (95%CI; 1.01\u20134.95), P = 0.046] and prior revascularization [HR 2.70 (95%CI 1.21\u20136.01), P = 0.015] were identified as being associated with a higher incidence of DLF. Absolute FFR values in FFR negative lesions in DM patients are not predictive of DLF (receiver operating characteristics curve analysis: area under the curve: 0.57 \ub1 0.06, 95%CI 0.46\u20130.69). Conclusions: In DM patients with FFR negative lesions, insulin requiring DM and prior revascularization are predictors for DLF. In contrast to non-DM patients, no predictive relationship between absolute negative FFR values (ranging >0.80\u20131.00) and the risk of DLF exists in DM patients

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 \u201cDAPT-STEMI trial\u201d

Background 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. Hypothesis Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. Study design 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. Summary 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

Fractional Flow Reserve\u2013Guided Deferred Versus Complete Revascularization in Patients With Diabetes Mellitus

To assess the safety and efficacy of deferred versus complete revascularization using a fractional flow reserve (FFR)\u2013guided strategy in patients with diabetes mellitus (DM), we analyzed all DM patients who underwent FFR-guided revascularization from January 1, 2010, to December 12, 2013. Patients were divided into 2 groups: those with 651 remaining FFR-negative (>0.80) medically treated lesions [FFR( 12)MT] and those with only FFR-positive lesions ( 640.80) who underwent complete revascularization [FFR(+)CR] and were followed until July 1, 2015. The primary end point was the incidence of major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), target lesion (FFR assessed) revascularization, and rehospitalization for acute coronary syndrome. A total of 294 patients, 205 (69.7%) versus 89 (30.3%) in FFR( 12)MT and FFR(+)CR, respectively, were analyzed. At a mean follow-up of 32.6 \ub1 18.1\ua0months, FFR( 12)MT was associated with higher MACE rate 44.0% versus 26.6% (log-rank p\ua0=\ua00.02, Cox regression\u2013adjusted hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.21 to 3.33, p\ua0<0.01), and\ua0driven by both safety and efficacy end points: death/MI (HR 2.02, 95% CI 1.06 to 3.86, p\ua0= 0.03), rehospitalization for acute coronary syndrome (HR 2.06, 95% CI 1.03 to 4.10, p\ua0= 0.04), and target lesion revascularization (HR 3.38, 95% CI 1.19 to 9.64, p\ua0= 0.02). Previous MI was a strong effect modifier within the FFR( 12)MT group (HR 1.98, 95% CI 1.26 to 3.13, p <0.01), whereas this was not the case in the FFR(+)CR group (HR 0.66, 95% CI 0.27 to 1.62, p\ua0= 0.37). Significant interaction for MACE was present between FFR groups and previous MI (p\ua0= 0.03). In conclusion, in patients with DM, particularly those\ua0with previous MI, deferred revascularization is associated with poor medium-term outcomes. Combining FFR with imaging techniques may be required to guide our treatment strategy in these patients with high-risk, fast-progressing atherosclerosis

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Polymer-based or polymer-free stents in patients at high bleeding risk

Background: polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. Methods: in an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. Results: a total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority). Conclusions: among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.)

Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial†

Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results The nominal change in the total atheroma volume (adjusted means) was −2.71, −3.13, −1.50, and −3.05 mm3 with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, −0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was −0.022, −0.036, −0.022, and −0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was −0.51, 2.65, 0.71, and −0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2; Trial registration number: NCT0120183

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients.</p> <p>Methods</p> <p>In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen.</p> <p>Discussion</p> <p>The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI.</p> <p>Trial registration</p> <p>ClincalTrials.gov number <a href="http://www.clinicaltrials.gov/ct2/show/NCT01267734">NCT01267734</a>.</p