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It is still a matter of debate which patients with acute inferior myocardial infarction are at increased risk of developing right ventricular (RV) myocardial infarction (RVMI). Cardiac magnetic resonance imaging (CMRI) with late enchancement (LE) is regarded as the gold standard for RVMI assessment. We aimed to determine the impact of initial angiographic status and salutary effect of primary percutaneous coronary intervention (PCI) on the presence of RVMI. In 114 patients undergoing emergency angiography and primary PCI of right coronary artery, 3-5 days after index PCI, LE CMRI was performed for assessing the RVMI. Forty-eight patients (42%) demonstrated RVMI. Multivariate regression analysis identified TIMI flow <2 in at least one RV branch after PCI as an independent angiographic predictor of RVMI [odds ratio (OR) 143.00, 95% confidence interval (CI) 18.10-1130.05, p < 0.001]. ST-segment elevation ≥ 1 mm in V4R was present in 83 (73%). TIMI flow <3 in at least one RV branch before PCI (OR 4.07, 95% CI 1.24-13.33, p = 0.02) was independent angiographic predictor of ST-segment elevation ≥ 1 mm in V4R. The only predictor of RVMI was TIMI flow <2 in at least one RV branch after PCI. ST-segment elevation ≥ 1 mm in V4R is caused by TIMI <3 flow in at least one RV branch before index PCI.

There is a critical need for alternative, potent agents that can reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with heterozygous familial hyperlipidemia and statin intolerance and those not reaching lipid-lowering treatment goals who are at high risk for cardiovascular (CV) events. The first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was approved in July 2015 by the US Food and Drug Administration as an adjunct to diet and maximally tolerated statin therapy for treatment of adults with heterozygous familial hyperlipidemia or clinical atherosclerotic CV disease, who require additional lowering of LDL-C levels. In clinical trials, PCSK9 inhibitors have been shown to reduce LDL-C levels by as much as 60% to 70% when administered as monotherapy or as an add-on treatment to statins and other lipid-lowering therapies. In studies of PCSK9 genetic mutations, loss of function in the PCSK9 allele was associated with a relative decrease of 88% in the risk for atherosclerotic CV events during 15 years of patient follow-up. The use of PCSK9 inhibitors may eventually support the LDL-C hypothesis that the lower the LDL-C level, the lower the CV risk. Although some recent clinical practice guidelines have deemphasized the importance of numeric LDL-C targets, many clinicians are reluctant to discard them, and this position is supported by recent clinical evidence. We eagerly await the results of the ODYSSEY, FOURIER, and SPIRE clinical outcome trials, which we anticipate will provide further validation that "lower is better" with respect to reducing LDL-C levels and improving clinical outcomes.

Background: The TAXUS Element (ION) platinum chromium paclitaxel-eluting stent (PtCr-PES) incorporates a thin (81 μm) strut design with a similar polymer and drug dose density as prior PES. The pivotal PERSEUS trial program consisted of two studies: PERSEUS Workhorse (WH) and PERSEUS Small Vessel (SV). The PERSEUS WH trial demonstrated the PtCr-PES to be non-inferior to the predicate TAXUS Express PES (TE-PES) for target lesion failure (TLF) at 1 year and in-segment angiographic percent diameter stenosis at 9 months. The PERSEUS SV trial demonstrated the PtCr-PES to be superior to a historical bare metal stent (BMS) for angiographic late lumen loss at 9 months. Long-term (5-year) clinical outcomes following PtCr-PES have not been previously reported., Methods: PERSEUS WH was a prospective, Bayesian, 3:1 randomized (PtCr-PES vs. TE-PES) trial in patients with lesion length ≤28 mm and vessel diameter ≥2.75 to ≤4.0 mm. PERSEUS SV was a prospective, single-arm trial in patients with lesion length ≤20 mm and vessel diameter ≥2.25 to <2.75 mm comparing PtCr-PES to a matched historical BMS control., Results: Among randomized subjects in the PERSEUS WH study, clinical event rates at 5 years were similar between treatment groups, including TLF (12.9% TE-PES vs. 12.1% PtCr-PES; P = 0.66). In the PERSEUS SV study, 5-year rates of MACE, and TLF were significantly lower for PtCr-PES (vs. BMS) following adjustment for baseline characteristics and were primarily due to lower target lesion revascularization rates (27.2% BMS vs. 14.9% PtCr-PES; P = 0.049)., Conclusions: At 5 years, the PtCr-PES provides efficacy and safety that is comparable to the TE-PES and superior efficacy with similar safety when compared with BMS in smaller caliber vessels. Cumulative stent thrombosis rates remained low and similar through 5 years for both DES platforms., (© 2015 Wiley Periodicals, Inc.)

Background: In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes., Methods: In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year., Results: Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13)., Conclusions: In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III ClinicalTrials.gov number, NCT01751906.).

The advent of fully bioresorbable stent technology and specifically the ABSORB™, a bioresorbable vascular scaffold (BVS) stent, is heralded as breakthrough technology in the current era of percutaneous coronary interventions. This article reviews the current understanding of this technology along with the clinical evidence from trials and registries of ABSORB BVS that included patients with both simple as well as more complex "real-world" coronary lesions. In addition, considering the current limitations of this device-mostly associated with the mechanical properties of the polymeric scaffold structure-a review of guidelines on successful implantation of the ABSORB BVS is presented. Although expert feedback suggests extensive use of this device in routine clinical practice outside the United States despite a paucity of data on long-term safety in this setting, attention to procedural details and implantation technique is obligatory to achieve optimal clinical outcomes., (© 2015 Wiley Periodicals, Inc.)

Objectives: This study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS., Background: Despite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES., Methods: Prospective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES- and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months., Results: Among 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference -1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference -1.8%, p = 0.053, noninferiority p < 0.001)., Conclusions: DES-treated subjects have long-term rates of stent thrombosis that are lower than BMS-treated subjects. (The Dual Antiplatelet Therapy Study [DAPT study]; NCT00977938)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Randomized trials have demonstrated progressive improvements in clinical and angiographic measures of restenosis with technologic iterations from balloon angioplasty to bare-metal stents and subsequently to drug-eluting stents (DES). However, the permanent presence of a metal stent prevents coronary vasomotion, autoregulation, and adaptive coronary remodeling. The limitations imposed by a permanent metal implant may be overcome with a bioresorbable scaffold. ABSORB III is a large-scale, multicenter, randomized trial designed to support US premarket approval of the ABSORB BVS platform and is the first study with sufficient size to allow valid examination of the relative clinical outcomes between metallic DES and bioresorbable scaffold., Design: ABSORB III (ClincalTrials.gov NCT01751906) will register approximately 2,262 patients and includes a lead-in phase (n = 50), the primary randomized analysis group (n = 2,000), an imaging cohort (n = 200), and a pharmacokinetic substudy (n = 12). In the primary analysis group, approximately 2,000 patients with up to 2 de novo native coronary artery lesions in separate epicardial vessels will be prospectively assigned in a 2:1 ratio to ABSORB BVS versus XIENCE everolimus-eluting stents (EES). The primary end point is target lesion failure (the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year, powered for noninferiority of ABSORB BVS compared to XIENCE EES. Clinical follow-up will continue for 5 years. Enrollment has been completed, and the principal results will be available in the fall of 2015., Conclusions: The large-scale ABSORB III randomized trial will evaluate the safety and effectiveness of ABSORB BVS compared to XIENCE EES in the treatment of patients with coronary artery disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Objectives: Sodium bicarbonate has been proposed for protection of the kidney from contrast-induced AKI (CIAKI). However, the effects of bicarbonate on long-term important clinical outcomes are uncertain., Design, Setting, Participants, & Measurements: In a prospective, double-blind, multicenter randomized clinical trial, 391 patients with an eGFR<45 ml/min per 1.73 m(2) undergoing elective coronary or peripheral angiography were randomized to an infusion with a high dose of isotonic sodium bicarbonate (target 2.0 mEq/kg) or a similar molar amount of isotonic sodium chloride. The primary outcome was a composite of mortality, dialysis, or a sustained 20% reduction in eGFR at 6 months., Results: There were 391 patients enrolled between March 2010 and May 2012. The incidence of the primary outcome was 14.9% in the bicarbonate group and 16.3% in the control group in the intention-to-treat population (P=0.78). There was also no difference in the incidence of CIAKI between the treatment groups (14.5% versus 12.1%, respectively; P=0.20). CIAKI was associated with a higher incidence of sustained loss of kidney function at 6 months compared with those without CIAKI (21.2% versus 7.7%, respectively; P=0.06)., Conclusions: High-dose sodium bicarbonate infusion in patients with eGFR<45 ml/min per 1.73 m(2) undergoing angiography did not demonstrate a difference in incidence of the composite of death, dialysis, or sustained 6-month reduction in eGFR or CIAKI compared with sodium chloride., (Copyright © 2015 by the American Society of Nephrology.)

Background: Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new lipid-lowering approach., Purpose: To assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia., Data Sources: MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015., Study Selection: Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia., Data Extraction: Two investigators independently extracted data on study characteristics and lipid and clinical outcomes, and rated risk of bias of trials. Prespecified primary end points were all-cause and cardiovascular mortality., Data Synthesis: Twenty-four RCTs comprising 10 159 patients were included. Compared with no antibody, treatment with PCSK9 antibodies led to marked reductions in low-density lipoprotein cholesterol levels (mean difference, -47.49% [95% CI, -69.64% to -25.35%]; P < 0.001] and other atherogenic lipid fractions, and it reduced all-cause mortality (odds ratio [OR], 0.45 [CI, 0.23 to 0.86]; P = 0.015; heterogeneity P = 0.63; I2 = 0%) and cardiovascular mortality (OR, 0.50 [CI, 0.23 to 1.10]; P = 0.084; heterogeneity P = 0.78; I2 = 0%). The rate of myocardial infarction was significantly reduced with use of PCSK9 antibodies (OR, 0.49 [CI, 0.26 to 0.93]; P = 0.030; heterogeneity P = 0.45; I2 = 0%), and increases in the serum creatine kinase level were reduced (OR, 0.72 [CI, 0.54 to 0.96]; P = 0.026; heterogeneity P = 0.65; I2 = 0%). Serious adverse events did not increase with administration of PCSK9 antibodies., Limitation: Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare., Conclusion: PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia., Primary Funding Source: CRC 1116 Masterswitches in Myocardial Ischemia, German Research Council DFG.

Background: The ODYSSEY COMBO I study (http://clinicaltrials.gov/show/NCT01644175) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia., Methods: This multicenter, phase 3, randomized (2:1 alirocumab vs placebo), double-blind, 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia. Alirocumab (75 mg every 2 weeks [Q2W]) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen. The alirocumab dose was increased to 150 mg Q2W (also 1 mL) at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥70 mg/dL. The primary efficacy end point was percent change in LDL-C from baseline to week 24 (intention-to-treat analysis)., Results: At week 24, estimated mean (95% CI) changes in LDL-C from baseline were -48.2% (-52.0% to -44.4%) and -2.3% (-7.6% to 3.1%) for alirocumab and placebo, respectively, an estimated mean (95% CI) difference of -45.9% (-52.5% to -39.3%) (P < .0001). Low-density lipoprotein cholesterol <70 mg/dL was achieved by 75% alirocumab versus 9% placebo patients at week 24. At week 12, 83.2% of evaluable alirocumab-treated patients remained on 75-mg Q2W. Treatment-emergent adverse events were comparable between groups., Conclusions: Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals, versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy. The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations., Objectives: This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI., Methods: The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding., Results: Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21)., Conclusions: Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study [The DAPT Study]; NCT00977938)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Outcomes of percutaneous coronary intervention (PCI) versus medical therapy (MT) in the management of stable ischemic heart disease (SIHD) remain controversial, with some but not all studies showing improved results in patients with ischemia. We sought to elucidate whether PCI improves mortality compared to MT in patients with objective evidence of ischemia (assessed using noninvasive imaging or its invasive equivalent). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PCI to MT in patients with SIHD. To maintain a high degree of specificity for ischemia, studies were only included if ischemia was defined on the basis of noninvasive stress imaging or abnormal fractional flow reserve. The primary outcome was all-cause mortality. We identified 3 RCTs (Effects of Percutaneous Coronary Interventions in Silent Ischemia After Myocardial Infarction II, Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2, and a substudy of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial) enrolling a total of 1,557 patients followed for an average of 3.0 years. When compared with MT in this population of patients with objective ischemia, PCI was associated with lower mortality (hazard ratio 0.52, 95% confidence interval 0.30 to 0.92, p=0.02). There was no evidence of study heterogeneity or bias among included trials. In this meta-analysis of published RCTs, PCI was shown to have a mortality benefit over MT in patients with SIHD and objective assessment of ischemia using noninvasive imaging or its invasive equivalent. In conclusion, this study provides insight into the management of a higher-risk SIHD population that is the focus of the ongoing International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Drug eluting stents with durable polymers may be associated with hypersensitivity, delayed healing, and incomplete endothelialization, which may contribute to late/very late stent thrombosis and the need for prolonged dual antiplatelet therapy. Bioabsorbable polymers may facilitate stent healing, thus enhancing clinical safety. The SYNERGY stent is a thin-strut, platinum chromium metal alloy platform with an ultrathin bioabsorbable Poly(D,L-lactide-co-glycolide) abluminal everolimus-eluting polymer. We performed a multicenter, randomized controlled trial for regulatory approval to determine noninferiority of the SYNERGY stent to the durable polymer PROMUS Element Plus everolimus-eluting stent., Methods and Results: Patients (n=1684) scheduled to undergo percutaneous coronary intervention for non-ST-segment-elevation acute coronary syndrome or stable coronary artery disease were randomized to receive either the SYNERGY stent or the PROMUS Element Plus stent. The primary end point of 12-month target lesion failure was observed in 6.7% of SYNERGY and 6.5% PROMUS Element Plus treated subjects by intention-to-treat (P=0.83 for difference; P=0.0005 for noninferiority), and 6.4% in both the groups by per-protocol analysis (P=0.0003 for noninferiority). Clinically indicated revascularization of the target lesion or definite/probable stent thrombosis were observed in 2.6% versus 1.7% (P=0.21) and 0.4% versus 0.6% (P=0.50) of SYNERGY versus PROMUS Element Plus-treated subjects, respectively., Conclusions: In this randomized trial, the SYNERGY bioabsorbable polymer everolimus-eluting stent was noninferior to the PROMUS Element Plus everolimus-eluting stent with respect to 1-year target lesion failure. These data support the relative safety and efficacy of SYNERGY in a broad range of patients undergoing percutaneous coronary intervention., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01665053., (© 2015 American Heart Association, Inc.)

Background: Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized., Methods and Results: Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively (P<0.001). Increasing severity of RV dysfunction as well as right atrial and RV enlargement were also associated with increased mortality (P<0.001). After multivariable adjustment, severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50-6.82; P=0.003) and moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02-2.52; P=0.042) remained associated with increased mortality as did right atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity (P=0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation., Conclusions: In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether concomitant treatment of TR in operable but high-risk patients with aortic stenosis is warranted., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01314313., (© 2015 American Heart Association, Inc.)

Importance: Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown., Objective: To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses., Design, Setting, and Participants: International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014., Interventions: Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11,648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES., Main Outcomes and Measures: Stent thrombosis, MACCE, and moderate or severe bleeding., Results: Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n = 4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P = .24), rates of MACCE were 4.04% vs 4.69% (n = 33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P = .72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n = 16 vs 7; P = .07), respectively. Among all 11,648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32% (n = 23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P < .001), rates of MACCE were 4.29% vs 5.74% (n = 244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P < .001), and rates of moderate/severe bleeding were 2.45% vs 1.47% (n = 135 vs 80; P < .001)., Conclusions and Relevance: Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested., Trial Registration: clinicaltrials.gov Identifier: NCT00977938.

Objectives: This study sought to assess the frequency and clinical impact of dual antiplatelet therapy (DAPT) nonadherence., Background: There are limited data on the impact of DAPT nonadherence during the first year after a second-generation drug-eluting stent placement., Methods: After successful Endeavor zotarolimus-eluting stent implantation, 2,265 patients were enrolled in a registry with limited exclusions and monitored during 12 months of prescribed DAPT. Predictors of any nonadherence (ANA) at 6 months were analyzed by multivariable analysis, and the association between ANA at 6 or 12 months with the endpoints of death, myocardial infarction, and stent thrombosis was assessed., Results: The study population included 30% female patients, 34% with diabetes and 36% with acute coronary syndromes. ANA occurred in 208 patients (9.6%) before 6 months and 378 patients (18.5%) before 1 year. Major bleeding (odds ratio [OR]: 12.83, 95% confidence interval [CI]: 7.55 to 21.80, p < 0.001) was the only predictor of ANA at 6 months. In time-dependent analyses, ANA before 6 months was associated with an increased risk of death or myocardial infarction (7.6% vs. 3.0%, p < 0.001) and a numerical increase in stent thrombosis (2.0% vs. 0.9%, p = 0.12). After adjustment for baseline differences, ANA within 6 months remained associated with death or MI (OR: 1.95, 95% CI: 1.02 to 3.75). ANA occurring after 6 months did not increase the risk of subsequent ischemic events., Conclusions: DAPT ANA occurs frequently and is associated with increased risk for thrombotic complications if it occurs within the first 6 months. Major bleeding was a significant correlate of DAPT ANA within 6 months. (EDUCATE: The MEDTRONIC Endeavor Drug Eluting Stenting: Understanding Care, Antiplatelet Agents and Thrombotic Events; NCT01069003)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Treatment with aspirin and a P2Y12 inhibitor is commonly used in patients with cardiovascular disorders. The overall effect of such treatment on all-cause mortality is unknown. In the Dual Antiplatelet Therapy (DAPT) Study, continuation of dual antiplatelet therapy beyond 12 months after coronary stenting was associated with an unexpected increase in non-cardiovascular death. In view of the potential public health importance of these findings, we aimed to assess the effect of extended duration dual antiplatelet therapy on mortality by doing a meta-analysis of all randomised, controlled trials of treatment duration in various cardiovascular disorders., Methods: We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomised controlled trials assessing the effect of extended duration versus no or short duration dual antiplatelet therapy, published before Oct 1, 2014. We did a meta-analysis to pool results with a hierarchical Bayesian random-effects model. The primary outcomes were hazard ratios comparing rates of all-cause, cardiovascular, and non-cardiovascular death., Findings: Including the DAPT Study, we identified 14 eligible trials that randomly assigned 69,644 participants to different durations of dual antiplatelet therapy. Compared with aspirin alone or short duration dual antiplatelet therapy (≤6 months), continued treatment was not associated with a difference in all-cause mortality (hazard ratio [HR] 1·05, 95% credible interval [CrI] 0·96-1·19; p=0·33). Similarly, cardiovascular (1·01, 0·93-1·12; p=0·81) and non-cardiovascular mortality (1·04, 0·90-1·26; p=0·66) were no different with extended duration versus short duration dual antiplatelet therapy or aspirin alone., Interpretation: Extended duration dual antiplatelet therapy was not associated with a difference in the risk of all-cause, cardiovascular, or non-cardiovascular death compared with aspirin alone or short duration dual antiplatelet therapy., Funding: None., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The TAXUS Liberté Post Approval Study (TL-PAS) contributed patients treated with TAXUS Liberté paclitaxel-eluting stent and prasugrel to the Dual Antiplatelet Therapy Study (DAPT) that compared 12 and 30 months thienopyridine plus aspirin therapy after drug-eluting stents., Methods and Results: Outcomes for 2191 TL-PAS patients enrolled into DAPT were assessed. The DAPT coprimary composite end point (death, myocardial infarction [MI], or stroke) was lower with 30 compared with 12 months prasugrel treatment (3.7% versus 8.8%; hazard ratio [HR], 0.407; P<0.001). Rates of death and stroke were similar between groups, but MI was significantly reduced with prolonged prasugrel treatment (1.9% versus 7.1%; HR, 0.255; P<0.001). The DAPT coprimary end point, stent thrombosis, was also lower with longer therapy (0.2% versus 2.9%; HR, 0.063; P<0.001). MI related to stent thrombosis (0% versus 2.6%; P<0.001) and occurring spontaneously (1.9% versus 4.5%; HR, 0.407; P=0.007) were both reduced with prolonged prasugrel. MI rates increased within 90 days of prasugrel cessation after both 12 and 30 months treatment. Composite Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) moderate or severe bleeds were modestly increased (2.4% versus 1.7%; HR, 1.438; P=0.234) but severe bleeds were not more frequent (0.3% versus 0.5%; HR, 0.549; P=0.471) in the prolonged treatment group., Conclusions: Prasugrel and aspirin continued for 30 months reduced ischemic events for the TAXUS Liberté paclitaxel-eluting stent patient subset from DAPT through reductions in MI and stent thrombosis. Withdrawal of prasugrel was followed by an increase in MI after both 12 and 30 months therapy. The optimal duration of dual antiplatelet therapy with prasugrel after TAXUS Liberté paclitaxel-eluting stent remains unknown, but appears to be >30 months., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00997503., (© 2014 American Heart Association, Inc.)

Background: The Dual Antiplatelet Therapy Study is large streamlined clinical trial designed to evaluate antiplatelet treatment strategies in a broadly inclusive population of subjects treated with coronary stents. Whether large streamlined trials can successfully include a representative group of study sites and patients has not been formally assessed., Methods and Results: Within the National Cardiovascular Data Registry CathPCI Registry, we compared characteristics and outcomes of hospitals participating versus not participating in the Dual Antiplatelet Therapy Study. We also compared clinical and procedural characteristics of trial subjects undergoing percutaneous coronary intervention (PCI) with drug-eluting stents to contemporaneous patients within the National Cardiovascular Data Registry CathPCI Registry. Standardized differences between groups were estimated. Between September 2009 and July 2011, 1.1 million PCIs were performed among 1276 hospitals, of which 309 (24.2%) participated in the Dual Antiplatelet Therapy Study. Participating hospitals were larger (468 versus 311 beds), more frequently located in urban settings (61.2% versus 42.6%), and had higher annual PCI volumes (858 versus 378) compared with nonparticipating hospitals, although hospital case mix and procedural outcomes were similar. Compared with CathPCI patients, trial patients undergoing PCI with drug-eluting stents were similar with respect to race, sex, and rates of diabetes mellitus, hypertension, and smoking, although they had lower rates of prior cardiovascular disease., Conclusions: Within the Dual Antiplatelet Therapy Study, clinical trial sites had similar patient case mix and clinical outcomes as nonparticipating sites. Although trial participants were representative of PCI patients with respect to race, sex and most comorbidities, they had a lower prevalence of chronic cardiovascular disease compared with registry patients. Although a streamlined cardiovascular clinical trial may successfully involve a large number of hospitals and rapidly enroll a diverse population of patients, differences between eligible patients and those actually enrolled remained., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00977938., (© 2014 American Heart Association, Inc.)

Purpose: The aim of the study was to assess the presence and spectrum of cardiac abnormalities identified by cardiac magnetic resonance (CMR) in women with hypereosinophilic syndrome (HES) of undefined etiology, who present with normal electrocardiography (ECG) and transthoracic echocardiography (TTE) and no history of heart disease., Methods: Ten women (mean age, 48 ± 14 years) with HES of undefined etiology, normal ECG and TTE, and no history of heart disease underwent CMR., Results: CMR showed cardiac abnormalities in 6 subjects. Five patients had nonischemic late gadolinium enhancement (LGE) lesions within the left ventricular (LV) myocardium, and 3 patients demonstrated CMR evidence of myocardial inflammation. The LV ejection fraction was 68.5 ± 5.7%, and the end-diastolic volume index was 62.7 ± 14.7 mL/m(2). The maximum measured blood eosinophil count correlated with LVLGE volume (r = 0.80, P = 0.006) and was 11374 ± 6242 cells/μL and 4114 ± 2972 cells/μL (P = 0.047) in patients with and without LGE lesions, respectively. The actual blood eosinophil count in subjects with and without CMR evidence of myocarditis was 1058 ± 520 cells/μL and 354 ± 377 cells/μL (P = 0.04), respectively., Conclusions: Despite normal ECG, TTE, and absence of history of heart disease, women with HES of unknown etiology frequently demonstrate cardiac abnormalities on CMR, the presence and extent of which are related to blood eosinophil count.

Background: Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain., Methods: Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding., Results: A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment., Conclusions: Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).

Objective(s): Evaluate efficacy/safety of olmesartan medoxomil (OM)/amlodipine (AML)/ hydrochlorothiazide (HCTZ) in Hispanic/Latino adults with hypertension., Design: Randomized, double-blind, 12-week, parallel-group study followed by a 40-week open-label extension phase., Setting: Clinical sites (317) in the United States and Puerto Rico., Patients or Participants: Individuals > or =18 years of age with mean seated blood pressure (BP) > or =140/100 or > or =160/90 mm Hg divided into Hispanic/Latino (369) and non-Hispanic/Latino (2122) subgroups., Interventions: Participants were randomized to OM 40/AML 10 mg, OM 40/HCTZ 25 mg, AML 10/HCTZ 25 mg, or OM 40/AML 10/HCTZ 25 mg during the double-blind phase. During the open-label extension, all participants received OM 40/AML 5/HCTZ 12.5 mg; participants not reaching BP goal within 2 weeks were randomly titrated to OM 40/AML 10/HCTZ 12.5 mg or OM 40/AML 5/HCTZ 25 mg, then to OM 40/AML 10/ HCTZ 25 mg after another 2 weeks., Main Outcome Measure: Change in mean seated diastolic BP (SeDBP) from baseline (double-blind phase)., Results: Triple-drug therapy vs the dual therapies resulted in greater mean reduction in SeBP (Hispanic/Latino: 35.0/20.9 mm Hg vs 27.8-30.9/15.3-17.7 mm Hg; non-Hispanic/Latino: 39.0/21.7 mm Hg vs 28.9-31.5/14.6-17.8 mm Hg) and enabled more participants to reach BP goal (Hispanic/Latino: 56.8% vs 40.6%-51.2%; non-Hispanic/Latino: 65.7% vs 33.8%-46.6%) irrespective of ethnicity. The efficacy of triple-drug therapy in achieving BP goal was sustained long-term (40-week open-label extension period) in Hispanic/Latino (63.3%) and non-Hispanic/ Latino (64.2%) participants. Triple-drug therapy was well tolerated in Hispanic/Latino and non-Hispanic/Latino participants., Conclusions: In this study, OM/AML/HCTZ was an effective treatment option in Hispanic/ Latino patients with hypertension.

Background: Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9) under investigation for treatment of hypercholesterolemia and reduction of cardiovascular events., Methods/design: The COMBO studies, part of the Phase 3 ODYSSEY clinical trial program, are designed to evaluate the efficacy and safety of alirocumab as add-on therapy to stable, maximally tolerated daily statin, with or without other lipid-lowering therapy (LLT), in a planned 966 patients with hypercholesterolemia at high cardiovascular risk. COMBO I ( http://clinicaltrials.gov/show/NCT01644175) is placebo-controlled, with a double-blind treatment period of 52 weeks, and 306 planned patients who may receive other LLTs in addition to statin therapy. COMBO II ( http://clinicaltrials.gov/show/NCT01644188) has a double-blind treatment period of 104 weeks, comparing alirocumab with ezetimibe in 660 planned patients receiving statin therapy (but no other LLTs). The primary efficacy endpoint is the difference between treatment arms in percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 24. Both studies utilized a starting dose of alirocumab 75 mg every 2 weeks (Q2W; administered as 1 mL solution via auto-injector). Patients with LDL-C levels ≥70 mg/dL after 8 weeks of treatment were up-titrated in a blinded manner at week 12 to alirocumab 150 mg Q2W (also 1 mL auto-injector)., Discussion: In conclusion, the COMBO studies will provide information on the long-term efficacy and safety of alirocumab in high-risk patients when administered in addition to maximally tolerated statin therapy, with a flexible dosing strategy which allows for individualized therapy based on the degree of LDL-C lowering needed to achieve the desired treatment response., Trial Registrations Combo I: NCT01644175 ( NCT01644175)., Combo Ii: NCT01644188 ( NCT01644188).

Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease, with limited treatment options. This analysis evaluated the effect of a monoclonal antibody to proprotein convertase subtilisin/kexin 9, alirocumab 150 mg every 2 weeks (Q2W), on Lp(a) levels in pooled data from 3 double-blind, randomized, placebo-controlled, phase 2 studies of 8 or 12 weeks' duration conducted in patients with hypercholesterolemia on background lipid-lowering therapy (NCT01266876, NCT01288469, and NCT01288443). Data were available for 102 of 108 patients who received alirocumab 150 mg Q2W and 74 of 77 patients who received placebo. Alirocumab resulted in a significant reduction in Lp(a) from baseline compared with placebo (-30.3% vs -0.3%, p <0.0001). Median percentage Lp(a) reductions in the alirocumab group were of a similar magnitude across a range of baseline Lp(a) levels, resulting in greater absolute reductions in Lp(a) in patients with higher baseline levels. Regression analysis indicated that <5% of the variance in the reduction of Lp(a) was explained by the effect of alirocumab on low-density lipoprotein cholesterol. In conclusion, pooled data from 3 phase 2 trials demonstrate substantive reduction in Lp(a) with alirocumab 150 mg Q2W, including patients with baseline Lp(a) >50 mg/dl. Reductions in Lp(a) only weakly correlated with the magnitude of low-density lipoprotein cholesterol lowering., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure trial, ultrafiltration (UF) removed volume more effectively than usual care (UC). Hypothetically, UF may be superior to UC due to increased sodium (Na) removal and less neurohormonal activation. We compared UF and UC in a randomized pilot trial of target weight guided therapy for acute decompensated heart failure (ADHF)., Subjects and Methods: Sixteen patients with ADHF were enrolled and target weights established prospectively, prior to randomization to UC or UF. UF patients did not receive diuretics and UC patients were all treated with a continuous furosemide drip. All urine and ultrafiltrate were collected and Na concentrations measured., Results: Similar volumes were removed in UC and UF groups (110105 mL and 107415 mL, respectively) and the UF group also produced 45325 mL of urine. Na concentration was 138±6 meq/L in the ultrafiltrate, 85±73 meq/L in the UC group's urine, and 26±23 meq/L in the UF group's urine. Given the relevant associated volumes, total meq of the Na removed was similar (1168 in UC vs. 1216 in UF). The UF group produced isotonic ultrafiltrate and a higher volume of dilute urine than anticipated., Conclusion: In a randomized pilot study of target weight guided therapy with UC or UF for ADHF, there were no differences in total volumes or Na removed, and lengths of hospital stays were similar. Isotonic fluid loss by UF was accompanied by the production of very dilute urine.

Coronary revascularization may be performed for relief of anginal symptoms or, in specific patient subgroups, to reduce the incidence of myocardial infarction and mortality. Achieving complete revascularization of all significantly obstructed coronary segments has been an established goal of coronary bypass graft surgery (CABG) and more recent data demonstrate a salutary effect of complete revascularization following percutaneous coronary intervention (PCI) on long-term clinical outcomes as well. Incomplete coronary revascularization is associated with increased mortality following both CABG and PCI, as well as with an increased incidence of myocardial infarction, repeat revascularization, and major adverse cardiovascular or cerebrovascular events following PCI. The relationship between completeness of revascularization and late adverse clinical outcomes is both qualitative and quantitative as reflected by the residual SYNTAX score (angiographic lesion complexity) following PCI. Thus, complete revascularization has evolved as an important objective for either CABG or PCI and the ability to achieve complete revascularization should enter into the decision algorithm for choice of revascularization modality.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability in developed nations, and it is rising rapidly in other parts of the developing world. Levels of low-density lipoprotein cholesterol (LDL-C) are directly correlated with atherogenic risk, and statin-based therapy is the most common management for these patients. However, many patients exhibit resistance to and/or adverse effects from statin therapy, and there is a need for adjunctive therapies or statin alternatives for these patients. The recently discovered human protein proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in LDL-C metabolism. PCSK9 promotes LDL receptor (LDL-R) degradation with a consequent reduction in LDL-R density and an increase in LDL-C levels. Consequently, PCSK9 inhibition to reduce LDL-C levels has become a primary focus for drug development. Numerous clinical trials focusing on monoclonal antibodies against PCSK9 have demonstrated efficacy equal to or greater than statin therapy for lowering LDL-C levels. Long-term trials are underway to assess safety, tolerability, and ability to reduce ASCVD.

Objectives: We compared the outcomes of patients treated with everolimus-eluting stents (EES) versus paclitaxel-eluting stents (PES) at 3 years from the large-scale randomized SPIRIT IV trial., Background: SPIRIT IV is the largest randomized trial comparing the outcomes of EES and PES. The present report represents the final long-term follow-up analysis from this study., Methods: A total of 3,687 patients were randomized 2:1 to EES or PES, stratified by presence of diabetes mellitus and lesion characteristics. Prespecified subgroups were compared for interaction with stent allocation. The primary end point was target lesion failure (TLF) (the composite of cardiac death, target vessel-related myocardial infarction [MI], or ischemia-driven target lesion revascularization)., Results: At 3 years, TLF occurred in 9.2% versus 11.7% of EES- and PES-treated patients (hazard ratio [HR] 0.78 [0.63-0.97], P = .02). The incidence of death or MI was 5.9% versus 9.1%, respectively (HR 0.67 [0.52-0.85], P = .001), and there was a 64% reduction in stent thrombosis (Academic Research Consortium definite or probable definition) with EES (0.59% vs 1.60%, HR 0.36 [0.18-0.72], P = .003). The difference in target lesion revascularization at 3 years did not reach statistical significance (6.2% vs 7.8%, respectively, HR 0.78 [0.60-1.01], P = .06). There was no significant interaction between treatment allocation and any of the subgroups, including diabetes., Conclusions: When compared with PES, EES provides durable and significant reduction in TLF, especially due to its enhanced safety profile, with lower rates of death or MI and stent thrombosis up to 3 years., (© 2013.)

Objectives: To investigate the safety and efficacy of durable polymer drug eluting stents (DES) and biodegradable polymer biolimus eluting stents (biolimus-ES)., Design: Network meta-analysis of randomised controlled trials., Data Sources and Study Selection: Medline, Google Scholar, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) database search for randomised controlled trials comparing at least two of durable polymer sirolimus eluting stents (sirolimus-ES) and paclitaxel eluting stents (paclitaxel-ES), newer durable polymer everolimus eluting stents (everolimus-ES), Endeavor and Resolute zotarolimus eluting stents (zotarolimus-ES), and biodegradable polymer biolimus-ES., Primary Outcomes: Safety (death, myocardial infarction, definite or probable stent thrombosis) and efficacy (target lesion and target vessel revascularisation) assessed at up to one year and beyond., Results: 60 randomised controlled trials were compared involving 63,242 patients with stable coronary artery disease or acute coronary syndrome treated with a DES. At one year, there were no differences in mortality among devices. Resolute and Endeavor zotarolimus-ES, everolimus-ES, and sirolimus-ES, but not biodegradable polymer biolimus-ES, were associated with significantly reduced odds of myocardial infarction (by 29-34%) compared with paclitaxel-ES. Compared with everolimus-ES, biodegradable polymer biolimus-ES were associated with significantly increased odds of myocardial infarction (by 29%), while Endeavor zotarolimus-ES and paclitaxel-ES were associated with significantly increased odds of stent thrombosis. All investigated DES were similar with regards to efficacy endpoints, except for Endeavor zotarolimus-ES and paclitaxel-ES, which were associated with significantly increased the odds of target lesion and target vessel revascularisations compared with other devices. Direction of results beyond one year did not diverge from the findings for up to one year follow-up. Bayesian probability curves showed a gradient in the magnitude of effect, with everolimus-ES and Resolute zotarolimus-ES offering the highest safety profiles., Conclusions: The newer durable polymer everolimus-ES and Resolute zotarolimus-ES and the biodegradable polymer biolimus-ES maintain the efficacy of sirolimus-ES; however, for safety endpoints, differences become apparent, with everolimus-ES and Resolute zotarolimus-ES emerging as the safest stents to date.

Background: The access to and growth of percutaneous coronary intervention (PCI) has not been fully explored with regard to geographic equity and need. Economic factors and timely access to primary PCI provide the impetus for growth in PCI centers, and this is balanced by volume standards and the benefits of regionalized care., Methods and Results: Geospatial and statistical analyses were used to model capacity, growth, and access of PCI hospitals relative to population density and myocardial infarction (MI) prevalence at the state level. Longitudinal data were obtained for 2003-2011 from the American Hospital Association, the U.S. Census, and the Centers for Disease Control and Prevention (CDC) with geographical modeling to map PCI locations. The number of PCI centers has grown 21.2% over the last 8 years, with 39% of all hospitals having interventional cardiology capabilities. During the same time, the US population has grown 8.3%, from 217 million to 235 million, and MI prevalence rates have decreased from 4.0% to 3.7%. The most densely concentrated states have a ratio of 8.1 to 12.1 PCI facilities per million of population with significant variability in both MI prevalence and average distance between PCI facilities., Conclusions: Over the last decade, the growth rate for PCI centers is 1.5× that of the population growth, while MI prevalence is decreasing. This has created geographic imbalances and access barriers with excess PCI centers relative to need in some regions and inadequate access in others.

Objectives: This study sought to investigate whether the everolimus-eluting stent (EES) is superior to the paclitaxel-eluting stent (PES) with respect to long-term individual clinical outcomes., Background: Individual studies have indicated a clinical advantage of coronary EES compared with PES with respect to restenosis and the composite endpoint of major adverse cardiac events. However, these trials were not powered for superiority in low-frequency event rates and have reported limited data beyond 1-year follow-up., Methods: We conducted a meta-analysis of the final 3-year results from the international SPIRIT (Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) II, III, and IV clinical trials. Individual patient data from 4,989 patients who were prospectively randomized to treatment with EES (n = 3,350) or PES (n = 1,639) were pooled for analysis., Results: At 3-year follow-up, EES was superior to PES in reducing the following event rates: target lesion failure (8.9% vs. 12.5%, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.59 to 0.85; p = 0.0002), all-cause mortality (3.2% vs 5.1%, HR: 0.65, 95% CI: 0.49 to 0.86; p = 0.003), myocardial infarction (3.2% vs. 5.1%, HR: 0.64, 95% CI: 0.48 to 0.85; p = 0.002), cardiac death or myocardial infarction (4.4% vs. 6.3%, HR: 0.70, 95% CI: 0.54 to 0.90; p = 0.005), ischemia-driven target lesion revascularization (6.0% vs. 8.2%, HR: 0.72, 95% CI: 0.58 to 0.90; p = 0.004), stent thrombosis (0.7% vs. 1.7%, HR: 0.45, 95% CI: 0.26 to 0.78; p = 0.003), and major adverse cardiac events (9.4% vs. 13.0%, HR: 0.71, 95% CI: 0.60 to 0.85; p = 0.0002). No interaction was present between stent type and the 3-year relative rates of target lesion failure across a broad range of subgroups, with the exception of diabetes and vessel (left anterior descending vs. other)., Conclusions: In this large dataset with 3-year follow-up, coronary implantation of EES compared with PES resulted in reduced rates of all-cause mortality, myocardial infarction, ischemia-driven target lesion revascularization, stent thrombosis, and target lesion failure. Further research is warranted to characterize possible interactions between stent type, diabetes, and vessel., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to evaluate the effect of smoking on the pharmacokinetics and pharmacodynamics (PD) of clopidogrel and prasugrel therapy., Background: Major randomized trial data demonstrated that nonsmokers experience less or no benefit from clopidogrel treatment compared with smokers (i.e., the "smokers' paradox")., Methods: PARADOX was a prospective, randomized, double-blind, double-dummy, placebo-controlled, crossover study of objectively assessed nonsmokers (n = 56) and smokers (n = 54) with stable coronary artery disease receiving aspirin therapy. Patients were randomized to receive clopidogrel (75 mg daily) or prasugrel (10 mg daily) for 10 days and crossed over after a 14-day washout. PD was assessed by using VerifyNow P2Y12 and vasodilator-stimulated phosphoprotein phosphorylation assays. Clopidogrel and prasugrel metabolite levels, cytochrome P450 1A2 activity, CYP2C19 genotype, and safety parameters were determined., Results: During clopidogrel therapy, device-reported inhibition of platelet aggregation (IPA) trended lower in nonsmokers than smokers (least squares mean treatment difference ± SE: 7.7 ± 4.1%; p = 0.062). Device-reported IPA was significantly lower in clopidogrel-treated smokers than prasugrel-treated smokers (least squares mean treatment difference: 31.8 ± 3.4%; p < 0.0001). During clopidogrel therapy, calculated IPA was lower and P2Y12 reaction units and vasodilator-stimulated phosphoprotein phosphorylation and platelet reactivity index were higher in nonsmokers than in smokers (p = 0.043, p = 0.005, and p = 0.042, respectively). Greater antiplatelet effects were present after prasugrel treatment regardless of smoking status (p < 0.001 for all comparisons)., Conclusions: PARADOX demonstrated lower clopidogrel active metabolite exposure and PD effects of clopidogrel in nonsmokers relative to smokers. Prasugrel was associated with greater active metabolite exposure and PD effects than clopidogrel regardless of smoking status. The poorer antiplatelet response in clopidogrel-treated nonsmokers may provide an explanation for the smokers' paradox. (The Influence of Smoking Status on Prasugrel and Clopidogrel Treated Subjects Taking Aspirin and Having Stable Coronary Artery Disease; NCT01260584)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Preclinical trials indicate that CD34+ cells represent an effective angiogenic stem cell component. Early-phase clinical trials suggest that intramyocardial administration of autologous CD34+ cells may improve functional capacity and symptoms of angina. RENEW is a pivotal phase 3 trial designed to determine the efficacy of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ stem cells for the treatment for patients with refractory angina and chronic myocardial ischemia. Patients (n = 444) receiving maximally tolerated antianginal therapies and lacking conventional revascularization options with Canadian Cardiovascular Society class III or IV angina and ischemia on stress testing will be randomized 2:1:1 to cell therapy (G-CSF-mediated stem cell mobilization, apheresis, and intramyocardial injection of 1 × 10(5) autologous CD34(+) cells/kg), active control (G-CSF-mediated stem cell mobilization, apheresis, and intramyocardial placebo injection), or open-label standard of care. The primary efficacy end point is change in exercise treadmill time in the treated vs active control patients, with 90% power to detect a 60-second difference in exercise time between cell-treated (n = 200) and active control (n = 100) patients. Key secondary end points include total number of anginal episodes per week and the incidence of independently adjudicated major adverse cardiac events and serious adverse events. RENEW will be the first adequately powered study aimed at definitively determining the efficacy of a cell therapy (intramyocardially delivered autologous CD34+ cells) for improvement of functional capacity in patients with refractory angina., (Copyright © 2013 Mosby, Inc. All rights reserved.)

The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate clinical and angiographic outcomes using a 1.20 mm diameter angioplasty catheter as part of a predilation strategy for coronary lesion treatment., Background: Development of an angioplasty catheter with low crossing profile and small balloon diameter represents an opportunity to facilitate percutaneous revascularization of complex coronary disease., Methods: Clinical and angiographic outcomes were evaluated following a predilation treatment strategy using a low profile, 1.20 mm angioplasty catheter. The primary end-point of procedural success was defined as successful device delivery, performance and lesion treatment without occurrence of perforation, flow-limiting dissection, reduction in baseline TIMI grade, or clinically significant arrhythmias, and with final achievement of TIMI 3 flow. In-hospital major adverse events were also determined., Results: Among 71 patients (83 lesions), angiographic characteristics included: de novo lesion, 75.9%; saphenous vein graft 9.6%; lesion length (mean ± standard deviation), 12.27 ± 5.96 mm; reference vessel diameter, 2.61 ± 0.57 mm; lesion classification B2/C, 59.0%; baseline TIMI 0/1 flow, 4.8%. Procedural success was achieved for 98.5% (66/67) of patients. Catheter delivery to the target lesion was achieved in all patients, and the rate of device success with luminal improvement after predilation was 96.2% (75/78). No acute procedural complications were observed, and in-hospital target lesion failure occurred in 6 patients (8.5%) related to peri-procedural non-Q wave myocardial infarction., Conclusions: Coronary lesion predilation with a low profile, 1.20 mm angioplasty catheter is associated with favorable procedural safety and efficacy and may represent an effective treatment for complex coronary anatomy., (© 2013, Wiley Periodicals, Inc.)

The aim of the study was to evaluate the presence and spectrum of cardiac abnormalities identified by cardiac magnetic resonance (CMR) in subjects in clinical remission of Churg-Strauss syndrome (CSS) and granulomatosis with polyangiitis (Wegener's) (WG) with normal ECG and transthoracic echocardiography (TTE). Eleven (7 females, 4 males, mean age 42.4 ± 9.6 years) CSS and 10 (4 females, 6 males, mean age 45.3 ± 10.9 years) WG patients in clinical remission with normal ECG and TTE underwent CMR. Segmental peak-systolic myocardial strain (εps) was measured using feature tracking cine-sequence based technique. Left ventricular (LV) ejection fraction, end-diastolic volume and myocardial mass indexes were 66.2 ± 5.8 %, 66.1 ± 6.6 ml/m(2), and 61.0 ± 8.9 g/m(2), respectively. No patient showed regional wall motion abnormalities and signs of myocarditis. Nine CSS and 8 WG patients demonstrated decreased segmental longitudinal, circumferential or radial εps and myocardial late gadolinium enhancement (LGE) (6 subendocardial, 10 midwall, 8 subepicardial) areas. In CSS and WG subjects with LVLGE lesions the mean LVLGE extent was 2.0 ± 1.6 % and 2.3 ± 1.5 % (p = 0.65), respectively. Segmental εps was decreased longitudinally (-11.8 ± 5.6 %) for subendocardial LGE, radially (13.7 ± 8.7 %) for subepicardial LGE, and circumferentially (-16.6 ± 4.2 %), longitudinally (-13.2 ± 5.5 %) and radially (18.8 ± 8.1 %) for midwall LGE, if compared to longitudinal (-22.7 ± 5.1 %), circumferential (-23.6 ± 5.6 %) and radial (34.2 ± 15.7 %) εps in controls (11 females, 10 males, mean age 43.9 ± 10.5 years) (all p < 0.01). Despite clinical remission, normal ECG and TTE, most CSS and WG patients demonstrate decreased segmental εps and non-ischemic LGE lesions without signs of myocarditis.