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Background— Effective progenitor cell recruitment to the ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent myocardial infarction are not defined. We tested the hypothesis that myocardial uptake of autologous CD34 + cells delivered via an intracoronary route after recent myocardial infarction is related to left ventricular (LV) ejection fraction (LVEF) and infarct size. Methods and Results— Thirty-one subjects (age, 36–69 years; 28 men) with primary percutaneous coronary intervention–treated anterior ST-segment–elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/dL [limits, 58–356 ng/dL]) and sustained LVEF depression at ≤45% were recruited. On day 10 (days 7–12), 4.3×10 6 (0.7–9.9×10 6 ) 99m Tc-extametazime–labeled autologous bone marrow CD34 + cells (activity, 77 MBq [45.9–86.7 MBq]) were administered transcoronarily (left anterior descending coronary artery). 99m Tc-methoxyisobutyl isonitrile (99 m Tc-MIBI) single-photon emission computed tomography before cell delivery showed 7 (2–11) (of 17) segments with definitely abnormal/absent perfusion. Late gadolinium-enhanced infarct core mass was 21.7 g (4.4–45.9 g), and infarct border zone mass was 29.8 g (3.9–60.2 g) (full-width at half-maximum, signal intensity thresholding algorithm). One hour after administration, 5.2% (1.7%–9.9%) of labeled cell activity localized in the myocardium (whole-body planar γ scan). Image fusion of labeled cell single-photon emission computed tomography with LV perfusion single-photon emission computed tomography or with cardiac magnetic resonance infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with late gadolinium-enhanced infarct border zone mass ( r =0.84, P r =0.76, P r =0.45, P =0.008) and late gadolinium-enhanced infarct core ( r =0.58 and r =0.84, P r =−0.07, P =0.68) or gated single-photon emission computed tomography LVEF ( r =−0.28, P =0.16). The correlation with cardiac magnetic resonance imaging-LVEF was weak ( r =−0.38; P =0.04). Conclusions— This largest human study with labeled bone marrow CD34 + cell transcoronary transplantation after recent ST-segment–elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone.

Medical therapies and revascularization play complementary roles in the treatment of patients with coronary atherosclerosis. In general, the degree of clinical benefit from percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), or medical therapy is proportional to the acuity of the clinical syndrome being treated. PCI for ST-segment elevation myocardial infarction1 and early angiography and revascularization for non–ST-segment elevation ACS2 have been demonstrated to improve survival and reduce myocardial infarction (MI) compared with medical therapy alone. Conversely, PCI in patients with stable coronary artery disease (CAD) has been proven to reduce symptoms and improve quality of life but has not been shown to prevent death or MI.3,4 Clinical trials and observational registries have demonstrated that objective evidence of myocardial ischemia is both qualitatively and quantitatively related to the subsequent risk of death and MI, and that greater reduction of ischemia with revascularization compared with medical therapy alone may correlate with improved event-free survival.5–7 This report examines the links between ischemia and prognosis, between revascularization and ischemia reduction, and therefore the likely relationship between revascularization and freedom from death/MI in patients with stable CAD. Ischemia documented by single photon emission computed tomography (SPECT) myocardial perfusion scanning (MPS) has been quantitatively correlated with the occurrence of cardiac death/MI.6 Among 10 627 consecutive patients evaluated for CAD by SPECT MPS, quantitative ischemia was directly proportional to 2-year mortality in medically treated patients, and the relative survival advantage provided by coronary revascularization (versus medical therapy alone) was directly related to the magnitude of ischemic burden (Figure 1).6,7 The observation that revascularization above a quantitative ischemic threshold involving 10% of the left ventricle (LV)7 may be associated with an incremental survival advantage has gained acceptance. A graded relationship between …

Item does not contain fulltext OBJECTIVES: The authors sought to identify and verify independent correlates of device thrombosis from an analysis of multicenter trials and registries. BACKGROUND: Recent analyses suggest an increased risk of device thrombosis with Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, California) implantation compared with metallic drug-eluting stents, and data from moderate size studies suggest a risk relationship to vessel size and technique. METHODS: From 8,771 consecutively treated patients, 105 patients (1.2%) were identified with scaffold thrombosis within 1 year of implantation. They were matched 2:1 with controls selected randomly from nonthrombosis patients. Data-restricted multiple logistic analysis was used to identify significant independent covariates of the outcome. RESULTS: Early (within 1 month) scaffold thrombosis occurred in 69 patients and late (1 to 12 months) thrombosis occurred in 36 patients. Modelling found significant correlations of thrombosis to be final minimal lumen diameter 1.1:1 balloon/scaffold ratio (OR: 2.3; p = 0.022), and reference vessel diameter

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. (J Interven Cardiol 2013;26:131–136)

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.

This study sought to determine whether patients with peripheral arterial disease (PAD) experience different reductions in ischemic event and increases in bleeding events with extended duration dual antiplatelet therapy versus those without PAD.Patients with PAD have increased ischemic and bleeding risks after coronary stenting.The DAPT (Dual Antiplatelet Therapy) study randomized 11,648 patients free from ischemic and bleeding events 12 months after coronary stenting to continued thienopyridine plus aspirin therapy for an additional 18 months versus aspirin therapy alone. The effects of continued thienopyridine on myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (death, MI, or stroke) and bleeding (GUSTO [Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries] moderate or severe) were assessed among those with versus without PAD.Among 11,648 randomized patients, 649 (5.57%) had PAD. Between 12 and 30 months, randomized patients with PAD had higher rates of MI/stent thrombosis (6.03% vs. 2.92%; p 0.001), major adverse cardiovascular and cerebrovascular events (11.65% vs. 4.62%; p 0.001), and bleeding (4.86% vs. 1.74%; p 0.001). Continued thienopyridine versus placebo was associated with consistent treatment effects for MI/stent thrombosis (with PAD, HR: 0.63; 95% CI: 0.32 to 1.22; without PAD, HR: 0.53; 95% CI: 0.42, 0.66; interaction p = 0.631), major adverse cardiovascular and cerebrovascular events (with PAD, HR: 1.06; 95% CI: 0.67 to 1.67; without PAD, HR: 0.70; 95% CI: 0.59 to 0.84; interaction p = 0.103), and bleeding (with PAD, HR, 1.82; 95% CI: 0.87 to 3.83; without PAD, HR: 1.66; 95% CI: 1.23 to 2.24; interaction p = 0.811).Among patients undergoing coronary stenting, those with PAD have more ischemic and bleeding events versus those without PAD. Extended duration dual antiplatelet therapy is associated with consistent ischemic benefit and bleeding harm among patients with and without PAD.

The purpose of this study was to evaluate the economic impact of the Absorb bioresorbable vascular scaffold compared with the Xience everolimus-eluting stent in patients undergoing percutaneous coronary intervention.The ABSORB III trial (Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease) demonstrated that the Absorb scaffold was noninferior to the Xience stent with respect to target lesion failure at 1 year. Whether health care costs differ between the Absorb scaffold and the Xience stent is unknown.We performed a prospective health economic study alongside the ABSORB III trial, in which patients undergoing percutaneous coronary intervention for stable or unstable angina were randomized to receive the Absorb scaffold (n = 1,322) or Xience stent (n = 686). Resource use data were collected through 1 year of follow-up. Costs were assessed using resource-based accounting (for procedures), MedPAR data (for other index hospitalization costs), and Medicare reimbursements (for follow-up costs and physician fees).Initial procedural costs were higher with the Absorb scaffold than the Xience stent ($6,316 ± 1,892 vs. $6,103 ± 1,895; p = 0.02), driven mainly by greater balloon catheter use and the higher cost of the scaffold in the Absorb group. Nonetheless, index hospitalization costs ($15,035 ± 2,992 for Absorb vs. $14,903 ± 3,449 for Xience; p = 0.37) and total 1-year costs ($17,848 ± 6,110 for Absorb vs. $17,498 ± 7,411 for Xience; p = 0.29) were similar between the 2 groups.Although initial procedural costs were higher with the Absorb scaffold, there were no differences in total 1-year health care costs between the 2 cohorts. Longer term follow-up is needed to determine whether meaningful cost savings emerge after scaffold resorption. (A Clinical Evaluation of Absorb™ BVS, the Everolimus-Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT01751906).

Although current everolimus-eluting coronary stents have shown improved event-free survival within the first year following implantation compared with bare-metal stents or earlier generation drug-eluting stents, they remain associated with an ongoing risk for adverse outcomes (thrombosis, myocardial infarction, and restenosis) beyond 1 year at rates similar to those observed following bare-metal stent deployment. This ongoing very late hazard has been attributed to the permanent presence of the metal frame and/or polymer in these stents. The Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) has been developed to provide mechanical support and drug-delivery functions similar to metallic drug-eluting stents, followed by complete resorption with recovery of more normal vascular structure and function, thus avoiding the limitations associated with permanent metallic endovascular prostheses. Absorb BVS has shown safety and efficacy in the dedicated clinical trial development program of Abbott Vascular and in an array of investigator-sponsored studies involving a broad spectrum of clinical (patient) as well as coronary anatomic complexity. Longer-term evidence, largely limited to single-arm studies, appears to reflect durable safety and efficacy and suggests Absorb BVS to be an attractive therapeutic option. Interim evidence from a series of randomized-clinical trials (RCTs) comparing Absorb BVS with the Xience cobalt-chromium metallic everolimus-eluting stent has shown noninferiority of Absorb BVS with respect to target lesion failure (composite occurrence of cardiac death, target vessel-related myocardial infarction, and ischemia-driven target lesion revascularization) beyond the first year, with no statistically significant differences in other safety/efficacy measures. However, concerns do exist in terms of increased rates of scaffold thrombosis, the risk for which may be mitigated by improved patient and lesion selection, procedural technique, and device iteration. We provide an overview of the evolution of percutaneous coronary intervention, in-vivo characterization of Absorb BVS resorption, and a summary with a critical evaluation of available evidence from RCTs, pooled analyses, and meta-analyses of RCTs for the safety and efficacy of Absorb BVS obtained primarily following the treatment of noncomplex coronary lesions in patients with stable ischemic heart disease and/or stabilized acute coronary syndromes.

The study sought to evaluate the efficacy and safety of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) (Abbott Vascular, Abbott Park, Illinois) in patients with diabetes mellitus.Randomized, controlled trials have demonstrated comparable clinical outcomes following percutaneous coronary intervention with either Absorb BVS or metallic Xience everolimus-eluting stent. However, these trials lack power required to provide reliable treatment effect estimates in this high-risk population.In a pre-specified, powered analysis, patients with diabetes who received ≥1 Absorb were pooled from the ABSORB II, III, and JAPAN randomized trials and from the single arm ABSORB EXTEND registry. The study composite primary endpoint was target lesion failure (TLF) at 1 year following Absorb BVS compared with a performance goal of 12.7%.Among 754 diabetic patients included in analysis (27.3% insulin treated), the 1-year TLF rate was 8.3% (upper 1-sided 95% confidence limit: 10.1%; p = 0.0001 vs. performance goal). Scaffold thrombosis (definite or probable) was observed in 2.3% of patients. Multivariable regression identified older age, insulin treatment, and smaller pre-procedure reference vessel diameter as significant independent predictors of 1-year TLF.The Absorb diabetic substudy suggests efficacy and safety of the Absorb BVS for treatment of patients with diabetes mellitus.

Background: Continued dual antiplatelet therapy and optimal medical therapy (OMT) improve outcomes in selected patient populations with established coronary heart disease, but whether OMT modifies the treatment effect of dual antiplatelet therapy is unknown. Methods: The DAPT (Dual Antiplatelet Therapy) Study, a double-blind trial, randomly assigned 11 648 patients who had undergone coronary stenting and completed 1 year of dual antiplatelet therapy without major bleeding or ischemic events to an additional 18 months of continued thienopyridine or placebo. OMT was defined as a combination of statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use in patients with an American College of Cardiology/American Heart Association class I indication for each medication. Per protocol, all patients were treated with 75 to 325 mg aspirin daily. End points included myocardial infarction, major adverse cardiovascular and cerebrovascular events, and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate or severe bleeding events. Results: Of 11 643 randomly assigned patients with complete medication data, 63% were on OMT. Between 12 and 30 months, continued thienopyridine reduced myocardial infarction in comparison with placebo in both groups (on OMT 2.1% versus 3.3%, hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.48–0.86; P =0.003; off OMT 2.2% versus 5.2%, HR, 0.41; CI, 0.29–0.58; P P =0.103). Comparing continued thienopyridine versus placebo, rates of major adverse cardiovascular and cerebrovascular events were 4.2% versus 5.0% among patients on OMT (HR, 0.82; CI, 0.66–1.02; P =0.077) and 4.5% versus 7.0% among those off OMT (HR, 0.63; CI, 0.49–0.82; P P =0.250); rates of bleeding for thienopyridine versus placebo in patients on OMT were 2.2% versus 1.0% (HR, 2.13; CI, 1.43–3.17; P P =0.189; interaction P =0.073). Overall, patients on OMT had lower rates of myocardial infarction (2.7% versus 3.7%, P =0.003), major adverse cardiovascular and cerebrovascular events (4.6% versus 5.7%, P =0.007), and bleeding (1.6% versus 2.5%, P P =0.171) and death (1.6% versus 1.9%, P =0.155) did not differ. Conclusions: Continued thienopyridine therapy reduced the rate of myocardial infarction regardless of OMT status and had consistent effects on reduction in major adverse cardiovascular and cerebrovascular events and increased bleeding. Clinical Trial Registration: URL: http://clinicaltrials.gov . Unique identifier: NCT00977938.

An increasing number of patients have refractory angina despite optimal medical therapy and are without further revascularization options. Preclinical studies indicate that human CD34

Dual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia but increases bleeding.To develop a clinical decision tool to identify patients expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI.Among 11,648 randomized DAPT Study patients from 11 countries (August 2009-May 2014), a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014).Twelve months of open-label thienopyridine plus aspirin, then randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin.Ischemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI.Among DAPT Study patients (derivation cohort; mean age, 61.3 years; women, 25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; -1 point for age 65 to younger than 75 years; and -2 points for age 75 years or older. Among the high score group (score ≥2, n = 5917), continued thienopyridine vs placebo was associated with reduced ischemic events (2.7% vs 5.7%; risk difference [RD], -3.0% [95% CI, -4.1% to -2.0%], P .001) compared with the low score group (score2, n = 5731; 1.7% vs 2.3%; RD, -0.7% [95% CI, -1.4% to 0.09%], P = .07; interaction P .001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; RD, 0.4% [95% CI, -0.3% to 1.0%], P = .26) compared with the low score group (3.0% vs 1.4%; RD, 1.5% [95% CI, 0.8% to 2.3%], P .001; interaction P = .02). Among PROTECT patients (validation cohort; mean age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n = 2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding.Among patients not sustaining major bleeding or ischemic events 1 year after PCI, a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts.clinicaltrials.gov Identifier: NCT00977938.

This study tested whether intramyocardial (IM) administration of mobilized, purified autologous CD34(+) cells would improve total exercise time (TET) and angina frequency in patients with refractory angina.IM administration of autologous CD34(+) cells has been associated consistently with improvements in functional capacity and angina symptoms in early phase clinical trials.RENEW (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina) was a randomized, double-blind, multicenter trial comparing IM CD34(+) administration with no intervention (open-label standard of care) or IM placebo injections (active control). The primary efficacy endpoint was change in TET at 12 months. Key secondary endpoints include changes in angina frequency at 3, 6, and 12 months, and TET at 3 and 6 months. The key safety analysis was the incidence of major adverse cardiovascular events through 24 months.The sponsor terminated the study for strategic considerations after enrollment of 112 of planned 444 patients. The difference in TET between patients treated with cell therapy versus placebo was 61.0 s at 3 months (95% confidence interval (CI): -2.9 to 124.8; p = 0.06), 46.2 s at 6 months (95% CI: -28.0 to 120.4; p = 0.22), and 36.6 s at 12 months (95% CI: -56.1 to 129.2; p = 0.43); angina frequency was improved at 6 months (relative risk: 0.63; p = 0.05). Autologous CD34(+) cell therapy seemed to be safe compared with both open-label standard of care and active control (major adverse cardiovascular events 67.9% [standard of care], 42.9% (active control), 46.0% [CD34(+)]).Due to early termination, RENEW was an incomplete experiment; however, the results were consistent with observations from earlier phase studies. These findings underscore the need for a definitive trial. (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34(+) Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina [RENEW]: NCT01508910).

Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients.We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort.The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation.In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) are an emerging therapy for dyslipidemia. Acute coronary events induce a dynamic increase of PCSK9 levels that may play a role in plaque vulnerability of both culprit and nonculprit coronary vessels. Growing evidence highlights a potential key role of PCSK9 antibodies in managing acute coronary syndrome. This review describes the influence of PCSK9 antibodies on plaque composition and instability, as well as the pharmacokinetic profile and the potential anti-inflammatory and antithrombotic mechanisms associated with PCSK9 inhibition that may confer benefits during the early phase of acute coronary syndrome. The authors posit a rationale for the use of PCSK9 antibodies in patients with acute coronary syndrome and highlight the need for further investigation in this area.

Background Although awareness of hypertension in Black patients has increased, blood pressure (BP) is frequently inadequately controlled. Objective This prespecified subgroup analysis of the TRINITY study evaluated the efficacy and safety of olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with the component dual-combination treatments in Black and non-Black study participants. Study Design TRINITY was a 12-week, randomized, double-blind, parallel-group evaluation. The first patient was enrolled in May 2008 and the last patient completed the study in February 2009. The study consisted of a 3-week washout period for participants receiving antihypertensive therapy and a 12-week double-blind treatment period. For the treatment phase, all study participants were stratified by age, race, and diabetes mellitus status and randomized to a treatment sequence that led to their final treatment assignment, which they received from weeks 4 to 12 (OM 40 mg/AML 10 mg/HCTZ 25 mg, OM 40 mg/AML 10 mg, OM 40 mg/HCTZ 25 mg, or AML 10 mg/HCTZ 25 mg). In the first 2 weeks of the double-blind treatment period, all participants received either dual-combination treatment or placebo. Participants assigned to dual-combination treatment continued treatment until week 4, and participants receiving placebo were switched at week 2 to receive one of the dual-combination treatments until week 4. At week 4, participants either continued dual-combination treatment or randomly received triple-combination treatment until week 12. Setting 317 clinical sites in the USA and Puerto Rico were included in the study. Patients Study participants eligible for randomization (N = 2492) were ≥18 years of age with mean seated blood pressure (SeBP) ≥140/100 mmHg or ≥160/90 mmHg (off antihypertensive medication). Intervention The intervention was with dual- or triple-combination antihypertensive treatment: OM 40 mg/AML 10 mg/HCTZ 25 mg, OM 40 mg/AML 10 mg, OM 40 mg/HCTZ 25 mg, or AML 10 mg/HCTZ 25 mg. Main Outcome Measure The primary efficacy variable was the change in least squares (LS) mean seated diastolic BP (SeDBP) from baseline to week 12. Secondary efficacy variables included the LS mean change in seated systolic BP (SeSBP), percentage of study participants reaching BP goal, and safety parameters. >Results In both Black and non-Black participants, triple-combination treatment resulted in significant and similar mean reductions in SeDBP and SeSBP (p≤0.0001 vs each dual-combination treatment) with a greater proportion of participants reaching BP goal compared with dual-combination treatments, regardless of race. Most treatment-emergent adverse events were mild or moderate in severity and no new safety concerns were identified. Conclusion Triple-combination treatment provided greater BP reductions than dual-combination treatments regardless of race. Clinical Trial Registration Registered at ClinicalTrials.gov as NCT00649389.

Background— A consensus definition for periprocedural myocardial infarction (MI) in coronary stent trials has not been established. Differences between a historic definition, based on modified World Health Organization (WHO) criteria, and a proposed universal definition have not been compared in a prospective clinical trial. Methods and Results— We randomly assigned 3687 patients with stable coronary artery disease to undergo stenting with either everolimus-eluting stents (2458 patients) or paclitaxel-eluting stents (1229 patients). Serial creatine kinase (CK) and CKMB or troponin measurements were obtained before and after stenting. MI was classified by protocol according to the WHO definition (total CK >2× normal with elevated CKMB) and post hoc according to the Universal/Academic Research Consortium (ARC) definition (CKMB or troponin >3× normal). Protocol MI was determined in 58 (1.6%) and universal/ARC MI in 287 (7.8%) patients within 48 hours post index procedure. There were substantial differences in frequency of universal/ARC MI if only CKMB (5.4%) or troponin (18.7%) data were included for evaluation. Total stent length was a strong predictor of both protocol and universal/ARC MI. Mortality at 2 years was low (2.3%) and was not different for either MI definition. The mortality rates did not increase with elevations of CKMB or troponin to >10× normal. Conclusions— There was a marked difference in periprocedural MI rates according to protocol or universal/ARC MI definitions. No association was present between periprocedural MI and mortality up to 2 years by either definition. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00307047.

Appropriate utilization of percutaneous coronary intervention (PCI) and medical therapy is deservedly a national healthcare policy priority for the United States. Because PCI is both common and costly, appraisal of appropriateness is warranted. The initial appropriate use criteria (AUC) have been developed for coronary revascularization procedures and investigators recently reported the appropriateness for the approximately 500,000 PCI procedures performed at centers participating in the National Cardiovascular Data Registry. The AUC have broad implications for both healthcare providers and our patients and will be used as the basis for indications, referral patterns, treatment options, physician education, shared decision-making, and reimbursement for years to come. While we acknowledge the importance of thoughtfully assessing appropriateness for all medical procedures including PCI, there are a number of concerns with the current AUC and methods used to report appropriateness that warrant expanded commentary.

J Clin Hypertens (Greenwich). 2012;14:149-157. ©2012 Wiley Periodicals, Inc. Most patients with hypertension require combination therapy in order to achieve blood pressure (BP) goals. This 40-week open-label extension of the 12-week double-blind Triple Therapy With Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY) evaluated the efficacy and safety of triple-combination treatments with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide (OM/AML/HCTZ) in 2112 participants with moderate to severe hypertension. Following 2 weeks of initial treatment with OM 40/AML 5/HCTZ 12.5 mg, participants not achieving BP goal were titrated to OM 40/AML 5/HCTZ 25 mg or OM 40/AML 10/HCTZ 12.5 mg on a randomized basis. At week 16, participants who did not achieve BP goal were further titrated to OM 40/AML 10/HCTZ 25 mg. At the end of the study, 44.5% to 79.8% of participants reached BP goal and the mean BP decreased from 168.6/100.7 mm Hg (baseline BP at randomization) to 125.0 to 136.8 mm Hg/77.8 to 82.5 mm Hg, depending on treatment. Long-term treatment with OM/AML/HCTZ was well tolerated and effective with no new safety concerns.

Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome) is a rare, systemic, small- to medium-sized vessel necrotizing vasculitis. The disease is characterized by common cardiac involvement, which remains the major determinant of mortality [(1)][1]. Glucocorticoids and

Recent analyses suggest an increased risk of very late scaffold thrombosis (VLST) beyond 1 year after implantation of Absorb BVS compared to metallic DES, but insights as to correlates of risk emanate from a limited number of patients. We sought to identify and verify independent correlates of

Objectives The aim of this study was to investigate the impact of reference vessel diameter (RVD) and lesion length (LL) on the relative safety and efficacy of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES). Background Lesion length and RVD are well-known predictors of adverse events after percutaneous coronary intervention. Methods Patient-level data were pooled from the randomized SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) II, III, IV and COMPARE (Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice) trials. Quantitative angiographic core laboratory data were available for 6,183 patients randomized to EES (n = 3,944) or PES (n = 2,239). Long lesions and small vessels were defined as LL >median (13.4 mm) and RVD ≤median (2.65 mm), respectively. Major adverse cardiac events (MACE) (consisting of cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization) were assessed at 2 years, according to stent type in 3 groups: short lesions in large vessels (group A, n = 1,297); long lesions or small vessels but not both (group B, n = 2,981); and long lesions in small vessels (group C, n = 1,905). Results The pooled 2-year MACE rates were 5.6%, 8.2%, and 10.4% in Groups A, B, and C, respectively (p Conclusions Patients with short lesions in large vessels have low rates of MACE at 2 years after treatment with either EES or PES. In higher-risk patients with long lesions and/or small vessels, EES results in significant improvements in both clinical safety and efficacy outcomes. (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions; NCT01016041 )

This 12-week, multicenter, randomized, double-blinded, 4-arm study in 440 patients with moderate to severe hypertension compared ambulatory blood pressure (ABP) responses with a triple-combination regimen (olmesartan medoxomil [OM] 40 mg, amlodipine besylate [AML] 10 mg, and hydrochlorothiazide [HCTZ] 25 mg) and its component dual-combination regimens at similar doses. At week 12, the triple combination resulted in a greater reduction in mean 24-hour systolic and diastolic blood pressure (-30.3/-18.0 mm Hg) compared with the 3 dual-combination regimens (OM 40 mg/AML 10 mg: -23.5/-13.9, OM 40 mg/HCTZ 25 mg: -23.9/-14.5, and AML 10 mg/HCTZ 25 mg: -18.5 mm Hg/-10.7 mm Hg; P

Objectives This study sought to compare the clinical outcomes of everolimus-eluting stents (EES) versus paclitaxel-eluting stents (PES) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). Background Although randomized trials have shown superiority of EES to PES, the safety and efficacy of EES in ACS is unknown. Methods We performed a patient-level pooled analysis from the prospective, randomized SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) II, III, IV, and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) trials in which 2,381 patients with ACS and 4,404 patients with stable CAD were randomized to EES or to PES. Kaplan-Meier estimates of death, myocardial infarction (MI), ischemia-driven target lesion revascularization, and stent thrombosis were assessed at 2 years and stratified by clinical presentation (ACS vs. stable CAD). Results At 2 years, patients with ACS compared with stable CAD had higher rates of death (3.2% vs. 2.4%, hazard ratio [HR]: 1.37 [95% confidence interval (CI): 1.02 to 1.85], p = 0.04) and MI (4.9% vs. 3.4%, HR: 1.45 [95% CI: 1.14 to 1.85], p = 0.02). In patients with ACS, EES versus PES reduced the rate of death or MI (6.6% vs. 9.3%, HR: 0.70 [95% CI: 0.52 to 0.94], p = 0.02), stent thrombosis (0.7% vs. 2.9%, HR: 0.25 [95% CI: 0.12 to 0.52], p = 0.0002), and ischemia-driven target lesion revascularization (4.7% vs. 6.2%, HR: 0.69 [95% CI: 0.48 to 0.99], p = 0.04). In patients with stable CAD, EES reduced the rate of death or MI (4.5% vs. 7.1%, HR: 0.62 [95% CI: 0.48 to 0.80], p = 0.0002), stent thrombosis (0.7% vs. 1.8%, HR: 0.34 [95% CI: 0.19 to 0.62], p = 0.0002), and ischemia-driven target lesion revascularization (3.9% vs. 6.9%, HR: 0.55 [95% CI: 0.42 to 0.73], p Conclusions Treatment with EES versus PES provides enhanced safety and efficacy regardless of the acuity of the clinical syndrome being treated and appears to mitigate the increased risk of stent thrombosis associated with ACS. (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions [SPIRIT II]; NCT01016041 )

Stent design, metal alloy composition, and strut thickness may influence late lumen loss and clinical outcomes after bare metal stent deployment; however, their impact on outcomes after drug-eluting stent deployment is unknown. Although the TAXUS Liberté and ION paclitaxel-eluting stents use similar polymer and drug, the ION stent incorporates a novel thin-strut platinum chromium metal alloy and cell design. We therefore compared patient-level data from 2,298 subjects enrolled into the TAXUS ATLAS (TAXUS Liberté) and PERSEUS (ION) clinical trials. Propensity-score (1:1) matching was performed to adjust for covariate imbalance between stent types. Twelve-month major adverse cardiac events were less frequent after use of the ION compared to the TAXUS Liberté (12.7% vs 8.3%, p0.001, unadjusted; 12.0% vs 7.5%, p = 0.007, propensity matched) largely because of decreased non-Q-wave myocardial infarction (MI; 2.9% vs 1.4%, p = 0.01, unadjusted; 3.2% vs 0.9%, p = 0.004, propensity matched). The MI difference was predominantly periprocedural and in patients treated with a single stent. In conclusion, this exploratory post hoc analysis demonstrated that the ION was associated with fewer adverse clinical events than the TAXUS Liberté because of decreased non-Q-wave MI. Stent platform-related variables may influence clinical outcomes after drug-eluting stent use despite similar polymer and drug elution. Differences in adjunctive pharmacotherapy and/or stenting technique may also be contributory.

Objectives We sought to determine whether the differences in outcomes present between everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) IV trial at 1 year were sustained with longer-term follow-up. Background In the SPIRIT IV trial, patients undergoing percutaneous coronary intervention who were randomized to EES compared with PES experienced lower 1-year rates of target lesion failure (cardiac death, target vessel myocardial infarction [MI], or ischemia-driven target lesion revascularization [TLR]), with significant reductions in the individual rates of MI, TLR, and stent thrombosis. Methods We prospectively randomized 3,687 patients with up to 3 noncomplex previously untreated native coronary artery lesions to EES versus PES at 66 U.S. sites. Follow-up through 2 years is complete in 3,578 patents (97.0%). Results Treatment with EES compared with PES reduced the 2-year rates of TLF (6.9% vs. 9.9%, p = 0.003), all MI (2.5% vs. 3.9%, p = 0.02), Q-wave MI (0.1% vs. 0.8%, p = 0.002), stent thrombosis (0.4% vs. 1.2%, p = 0.008), and ischemia-driven TLR (4.5% vs. 6.9%, p = 0.004), with nonsignificantly different rates of all-cause and cardiac mortality. Between 1 year and 2 years, there were no significant differences in adverse event rates between the 2 stent types. Conclusions In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, the benefits of EES compared with those of PES present at 1 year were sustained at 2 years. (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System; NCT01016041 )

Dual antiplatelet therapy with aspirin and clopidogrel is associated with a significant reduction in vascular ischemic events; however, gastrointestinal bleeding events are a major concern in high-risk and older patients. Clinical practice guidelines recommend combination therapy with proton pump inhibitors (PPI) and dual antiplatelet therapy to attenuate gastrointestinal bleeding risk. In addition, high on-treatment platelet reactivity has been associated with recurrent ischemic events. Whether or not the pharmacological interaction between clopidogrel and PPI, which results in diminished antiplatelet effect, adversely influences clinical efficacy is highly controversial and the subject of debate. Based on largely anecdotal post-hoc analyses, the U.S. Federal Drug Administration's and European Medicines Agency's recommendations discourage PPI use (particularly omeprazole) in patients treated with clopidogrel. However, many American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions experts do not support change in clinical practice guidelines recommendations without adequately powered, prospective, randomized clinical trial data.

Ticagrelor is a reversibly binding, noncompetitive, direct-acting, orally administered P2Y12-receptor antagonist and is a credible alternative to clopidogrel in the treatment of patients with acute coronary syndrome. Ticagrelor therapy has been associated with rapid onset and faster offset of actions and greater and consistent platelet inhibition. In the Study of Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor significantly reduced the rate of the combined end point of cardiovascular death, myocardial infarction or stroke in acute coronary syndrome patients compared with clopidogrel. A major potential benefit of ticagrelor is the unprecedented reduction in mortality among acute coronary syndrome patients. An additional important observation was similar CABG-related bleeding events in ticagrelor (vs clopidogrel)-treated patients despite the fact that ticagrelor provides more potent P2Y12-receptor blockade.

AIMS Small reference vessel diameter predicts adverse outcomes following coronary stenting. TAXUS Express and TAXUS Liberte paclitaxel-eluting stents (PES) reduce restenosis compared to bare metal stents (BMS) in small diameter vessels. TAXUS Element is a novel thin-strut, platinum chromium stent designed to enhance visibility, conformability, and drug delivery in small diameter vessels. METHODS AND RESULTS The PERSEUS Small Vessel (SV) prospective, single-arm, superiority trial evaluates the TAXUS Element PES in 224 subjects with target lesion length≤20 mm and vessel diameter≥2.25 to

Aims: Although clinical trials have demonstrated superior clinical efficacy and improved safety of the everolimus-eluting stent (EES) compared with paclitaxel-eluting stents (PES) the clinical, angiographic and procedural factors associated with adverse clinical outcomes following drug-eluting stent (DES) deployment have not been carefully analysed. Methods and results: We performed a patient-level pooled database analysis from the SPIRIT II, III, IV and COMPARE prospective randomised (EES versus PES) trials which enrolled 6,789 patients undergoing coronary stenting with follow-up through two years. To determine independent predictors of death, myocardial infarction (MI), ischaemia-driven revascularisation (target lesion [ID-TLR] or target vessel [ID-TVR]), and major adverse cardiovascular events ([MACE]; composite occurrence of cardiovascular death, MI, ID-TLR), we analysed clinical, angiographic and procedural variables using Cox proportional hazard stepwise regression analysis. Treatment with EES (versus PES) was a powerful, independent predictor of relative freedom from MI (HR [95% CI]= 0.54 [0.41, 0.71]; p

Significant evolution in catheter-based technologies for percutaneous coronary intervention has occurred since the introduction of coronary balloon angioplasty by Andreas Grüntzig in 1977. As balloon angioplasty was supplanted by bare metal stents and subsequently drug-eluting stents (DES), randomized comparative clinical trials have demonstrated a progressive decline in both angiographic and clinical restenosis with each technologic iteration. Following widespread clinical use of DES, multiple safety issues have been identified in late follow-up that have prompted efforts toward development of bioresorbable polymers and polymer-free metal platforms, as well as completely resorbable DES platforms. The ultimate goal of these efforts is to provide safe and durable coronary patency. The promise of bioresorbable DES platforms includes the additional benefits of recovery in normal autoregulatory as well as microvascular function, the capacity for late luminal enlargement/expansive remodeling, and the potential for reducing the requirement for prolonged dual antiplatelet therapy.

Objectives We compared the safety and efficacy of the XIENCE V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) with the TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stent (PES) among the large cohort of randomized diabetic patients enrolled in the SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) trial. Background Diabetes mellitus remains a significant predictor of adverse clinical outcomes after percutaneous coronary intervention with drug-eluting stents, and the comparative outcomes of different drug-eluting stents in diabetic patients remains ill-defined. Methods In the SPIRIT IV trial, 3,687 patients with up to 3 de novo native coronary artery lesions were prospectively randomized 2:1 to receive EES or PES. Randomization was stratified by the presence of diabetes and lesion complexity. The primary end point was the occurrence of target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year. Clinical outcomes were evaluated in randomized diabetic (n = 1,185 [786 EES; 399 PES]) and nondiabetic patients (n = 2,498 [1,669 EES; 829 PES]). Results The EES compared with PES reduced TLF in nondiabetic patients (3.1% vs. 6.7%, p interaction = 0.02) was observed. Conclusions In the SPIRIT IV randomized trial, EES compared with PES provided similar clinical outcomes in diabetic patients and superior clinical outcomes in nondiabetic patients at 1 year. (SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT00307047)

REPRISE III is the first large randomized comparison of 2 TAVR platforms: the mechanically-expanded Lotus valve (Boston Scientific, Marlborough, MA) and self-expanding CoreValve (Medtronic, Dublin, Ireland). In aortic stenosis patients with high/extreme surgical risk, Lotus was noninferior to

The Absorb everolimus-eluting PLLA-based bioresorbable vascular scaffold (BVS) provides 1-year drug delivery and mechanical support functions similar to metallic DES, followed by complete bioresorption in ∼3 years with recovery of vascular structure and function. The large-scale pivotal US

The addition of clopidogrel to aspirin treatment reduces ischemic events in a wide range of patients with cardiovascular disease. However, recurrent ischemic event occurrence during dual antiplatelet therapy, including stent thrombosis, remains a major concern. Platelet function measurements during clopidogrel treatment demonstrated a variable and overall modest level of P2Y(12) inhibition. High on-treatment platelet reactivity to adenosine diphosphate (ADP) was observed in selected patients. Multiple studies have now demonstrated a clear association between high on-treatment platelet reactivity to ADP measured by multiple methods and adverse clinical event occurrence. However, the routine measurement of platelet reactivity has not been widely implemented and recommended in the guidelines. Reasons for the latter include: 1) a lack of consensus on the optimal method to quantify high on-treatment platelet reactivity and the cutoff value associated with clinical risk; and 2) limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes. This review provides a consensus opinion on the definition of high on-treatment platelet reactivity to ADP based on various methods reported in the literature and proposes how this measurement may be used in the future care of patients.

Objective: Secondary, prespecified analysis of a single-arm, open-label study evaluating the efficacy of olmesartan medoxomil (OM) plus hydrochlorothiazide (HCTZ) in patients with hypertension and type 2 diabetes. Methods: After placebo run-in, 192 patients received OM 20 mg/day for 3 weeks. If blood pressure (BP) remained ≥120/70 mmHg, patients were uptitrated every 3 weeks to OM 40 mg/day, OM/HCTZ 40/12.5 mg/day, and OM/HCTZ 40/25 mg/day. Efficacy was evaluated by 24-hour ambulatory BP monitoring. Secondary endpoints included changes in ambulatory systolic BP (SBP) and diastolic BP (DBP) during daytime (08:00 to 16:00) and nighttime (22:00 to 06:00), as well as achievement of prespecified ambulatory BP targets in the total cohort and subgroups based on gender, race, hypertension severity, and age (≥65 or Results: At baseline, mean ambulatory BP was 151.2 ± 12.7/87.6 ± 9.0 mmHg during the daytime and 140.3 ± 13.1/78.1 ± 8.6 mmHg during the nighttime. Mean daytime and nighttime ambulatory BP was reduced from baseline by 22.3 ± 13.7/12.0 ± 8.9 mmHg and 18.8 ± 12.4/ 10.2 ± 7.2 mmHg, respectively. The reduction in daytime ambulatory SBP was 24.4 ± 11.8 mmHg in Blacks, 21.7 ± 14.2 mmHg in non-Blacks, 23.6 ± 12.3 mmHg in females, 21.2 ± 14.8 mmHg in males, 23.4 ± 11.6 mmHg in patients aged ≥65 years, and 21.9 ± 14.4 mmHg in those aged Conclusions: OM ± HCTZ effectively lowered ambulatory BP in patients with type 2 diabetes and hypertension, enabling them to achieve ambulatory BP targets during both the daytime and nighttime.

Elevated systolic BP (SBP) is a major contributor to cardiovascular disease. SBP control reduces the occurrence of stroke, heart failure, and cardiovascular and total mortality. The aim of this study was to analyze the magnitude of SBP reductions and the achievement of individual SBP targets in the original BENIFORCE study.An olmesartan medoxomil-based treatment algorithm was evaluated in a double-blind, placebo-controlled titration study in 276 patients with stage 1 (47.1%) or 2 (52.9%) hypertension. After placebo run-in, patients were randomized to placebo (12 weeks) or olmesartan medoxomil 20 mg/day (weeks 1-3). Olmesartan medoxomil was uptitrated to 40 mg/day (weeks 4-6), then olmesartan medoxomil/hydrochlorothiazide (HCTZ) 40/12.5 mg per day (weeks 7-9), and olmesartan medoxomil/HCTZ 40/25 mg per day (weeks 10-12) if BP remained ≥120/80 mmHg at any time interval.The BENIFORCE study was a multicenter (29 sites) study conducted between January and October 2007 in the US.In patients receiving olmesartan medoxomil-based therapy, 81.0%, 67.2%, and 46.6% of patients with stage 1 hypertension and 70.4%, 49.4%, and 23.5% of patients with stage 2 hypertension achieved SBP targets of140,130, and120 mmHg, respectively (all p0.01 vs placebo). The proportions of patients achieving SBP targets increased with escalating doses of olmesartan medoxomil and HCTZ, administered alone or in combination, and was highest for combination therapy. Similarly, escalating doses of olmesartan medoxomil or olmesartan medoxomil/HCTZ increased the proportion of patients achieving SBP reductions of15 but ≤30,30 but ≤45, and45 mmHg compared with placebo.An olmesartan medoxomil-based treatment algorithm effectively reduced SBP and achieved SBP targets in patients with stage 1 or 2 hypertension. This regimen resulted in80% of patients achieving SBP reductions of ≥15 mmHg while 44% achieved SBP reductions of30 mmHg.

Objectives The aim of this study was to evaluate the safety and efficacy of the novel platinum chromium TAXUS Element paclitaxel-eluting stent (PES) compared with the TAXUS Express PES (Boston Scientific, Natick, Massachusetts) in treating coronary artery stenoses. Background The TAXUS Element is a novel thin-strut (81 μm), platinum chromium alloy PES designed to improve radial strength, radiopacity, and deliverability, while safely providing comparable restenosis benefit compared with a previous-generation PES. Methods The PERSEUS (Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System) Workhorse (WH) trial is a prospective, randomized (3:1), controlled, multicenter study of the TAXUS Element (vs. TAXUS Express) PES for the treatment of de novo coronary atherosclerotic lesions ≤28 mm in length in reference vessels ≥2.75 to ≤4.0 mm in diameter. The primary end point was the 12-month rate of target lesion failure, and the secondary end point was 9-month angiographic in-segment percentage diameter stenosis. The study was powered to demonstrate noninferiority to TAXUS Express for both end points. Results The intent-to-treat analysis included 1,262 patients (320 TAXUS Express, 942 TAXUS Element). The TAXUS Element was noninferior to TAXUS Express with respect to both the incidence of target lesion failure (5.57% vs. 6.14%, respectively; difference: 0.57%; 95% credible interval: 1.85%; Bayesian posterior probability of noninferiority = 0.9996) and percentage diameter stenosis (ln[%DS] 3.09 vs. 3.12, respectively; difference: 0.03; 95% credible interval: 0.11; Bayesian posterior probability of noninferiority = 0.9970). No differences in clinical outcomes to 12 months were observed between stent treatments, and stent thrombosis was infrequent (0.3% Express, 0.4% Element). Conclusions At 1 year, the TAXUS Element is comparable in efficacy to the TAXUS Express PES. Furthermore, no safety concerns related to the novel platinum chromium alloy or stent design were observed. (A Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System for the Treatment of De Novo Coronary Artery Lesions; NCT00484315)

The loss-of-function hepatic cytochrome P450 (CYP) 2C19*2 allele has been associated with reduced clopidogrel active metabolite generation and higher ex vivo platelet reactivity to adenosine diphosphate. Independently, in post hoc analyses, CYP2C19*2 has been associated with worse clinical outcomes during clopidogrel therapy. The controversy surrounding the diminished effectiveness of clopidogrel in poor metabolizers, those having 2 loss-of-function alleles, has been recently highlighted in the “boxed warning” issued by the U.S. Food and Drug Administration. However, much of the variation in clopidogrel response is not explained by the CYP2C19*2 allele (the most frequent loss-of-function allele), and other factors, both genetic and nongenetic, are likely to be important contributors. High on-treatment platelet reactivity to adenosine diphosphate during clopidogrel therapy is a well-documented predictor of recurrent ischemic events in the percutaneous coronary intervention population. While platelet function is dynamic in individual patients because of the influence of variable external factors, the influence of the CYP2C19*2 allele is intrinsically constant. Thus, it may be reasonable to consider both genotyping and platelet function measurement to assess ischemic risk and to guide antiplatelet therapy. Prospective clinical trials to test new algorithms for optimal personalized antiplatelet therapy are needed to provide the evidence base required for the routine adoption of genotyping into clinical practice.

The aim of the present study was to use ambulatory blood pressure (BP) monitoring (ABPM) to determine the efficacy of a fixed-dose combination of amlodipine (AML) and olmesartan medoxomil (OM) over the 24-hour dosing interval. This 12-week, titrate-to-goal study was conducted in 185 patients with hypertension. Patients were initially treated with AML 5 mg/ day and uptitrated to AML/OM 5/20, 5/40, and 10/40 mg/day every 3 weeks if mean seated BP (SeBP) was ≥120/80 mmHg. The primary efficacy endpoint was the change from baseline in mean 24-hour systolic BP at week 12 as assessed by ABPM. At baseline, the mean 24-hour ambulatory BP (±standard deviation [SD]) was 144.8±11.1/85.7±7.9 mmHg. At week 12, the change from baseline in mean 24-hour ambulatory BP (±standard error of the mean [SEM]) was -21.4±0.8/-12.7±0.5 mmHg (p < 0.0001 versus baseline). At baseline, the mean SeBP (±SD) was 158.2±12.6/92.8±8.6 mmHg and at week 12, the mean SeBP change (±SEM) from baseline (last observation carried forward) was -24.1±1.1/-12.1±0.7 mmHg (p < 0.0001 versus baseline). Proportions of patients achieving mean 24-hour ambulatory BP prespecified study targets were 70.9% (

Previous studies have established the superiority of coronary everolimus-eluting stents over paclitaxel-eluting stents with respect to angiographic findings. However, these trials were not powered for superiority in clinical end points.We randomly assigned 3687 patients at 66 U.S. sites to receive everolimus-eluting stents or paclitaxel-eluting stents without routine follow-up angiography. The primary end point was the 1-year composite rate of target-lesion failure (defined as cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization).Everolimus-eluting stents were superior to paclitaxel-eluting stents with respect to the primary end point of target-lesion failure (4.2% vs. 6.8%; relative risk, 0.62; 95% confidence interval, 0.46 to 0.82; P=0.001). Everolimus-eluting stents were also superior with respect to the major secondary end point of the 1-year rate of ischemia-driven target-lesion revascularization (P=0.001) and were noninferior with respect to the major secondary end point of the 1-year composite rate of cardiac death or target-vessel myocardial infarction (P0.001 for noninferiority; P=0.09 for superiority). The 1-year rates of myocardial infarction and stent thrombosis were also lower with everolimus-eluting stents than with paclitaxel-eluting stents (1.9% vs. 3.1%, P=0.02 for myocardial infarction; 0.17% vs. 0.85%, P=0.004 for stent thrombosis). Target-lesion failure was consistently reduced with everolimus-eluting stents as compared with paclitaxel-eluting stents in 12 prespecified subgroups, except in the subgroup of patients with diabetes (6.4% vs. 6.9%, P=0.80).Everolimus-eluting stents, as compared with paclitaxel-eluting stents, resulted in reduced rates of target-lesion failure at 1 year, results that were consistent in all patients except those with diabetes, in whom the results were nonsignificantly different. (ClinicalTrials.gov number, NCT00307047.)

Paravalvular leak (PVL) following TAVR has been associated with worse long-term outcomes including an increased risk of mortality. REPRISE III was a large randomized trial comparing 2 contemporary TAVR devices: Lotus and CoreValve (CV). Lotus incorporates an adaptive seal designed to minimize PVL.

The BENIFICIARY (BENIcar safety and efFICacy evaluatIon: An open-label, single-ARm, titration study in patients with hypertension and tYpe 2 diabetes) study was conducted to evaluate the efficacy and safety of olmesartan medoxomil (OM) plus hydrochlorothiazide (HCTZ) in patients with hypertension and type 2 diabetes.After a placebo run-in period, 192 patients received OM 20 mg/day for 3 weeks. If blood pressure (BP) remainedor =120/70 mm Hg, patients were up-titrated to OM 40 mg/day for 3 weeks and subsequently (in 3-week intervals) to OM/HCTZ 40/12.5 mg/day, then OM/HCTZ 40/25 mg/day as necessary. Blood pressure was evaluated by mean 24-hour ambulatory BP monitoring (ABPM). The primary efficacy endpoint was the change in mean 24-hour ambulatory systolic BP (SBP) from baseline to Week 12. Secondary endpoints included: change in ambulatory diastolic BP (DBP) from baseline to Week 12; changes in ambulatory SBP and DBP during daytime, nighttime, and the last 2, 4, and 6 hours of the dosing interval; and achievement of prespecified ambulatory BP targets. CLINICAL TRIALS REGISTRY NUMBER: NCT00403481.Mean 24-hour ambulatory SBP and DBP decreased by 20.4 mm Hg and 11.1 mm Hg, respectively (both P0.0001 to baseline), and 61.6%, 47.1%, and 39.0% of patients reached the ambulatory BP targets of130/80 mm Hg,125/75 mm Hg, and120/80 mm Hg, respectively. The study medication was well tolerated with few adverse events: 67/192 patients (34.9%) experienced a treatment-emergent adverse event (TEAE) while 15/192 (7.8%) experienced a drug-related TEAE.In this open-label ABPM study, an OM +/- HCTZ based treatment regimen safely and significantly reduced BP in patients with hypertension and type 2 diabetes when assessed by 24-hour ABPM.

Background— Ticagrelor is the first reversibly binding oral P2Y 12 receptor antagonist. This is the first study to compare the onset and offset of platelet inhibition (IPA) with ticagrelor using the PLATO (PLATelet inhibition and patient Outcomes) trial loading dose (180 mg) with a high loading dose (600 mg) of clopidogrel. Methods and Results— In a multicenter, randomized, double-blind study, 123 patients with stable coronary artery disease who were taking aspirin therapy (75 to 100 mg/d) received ticagrelor (180-mg load, 90-mg BID maintenance dose [n=57]), clopidogrel (600-mg load, 75-mg/d maintenance dose [n=54]), or placebo (n=12) for 6 weeks. Greater IPA (20 μmol/L ADP, final extent) occurred with ticagrelor than with clopidogrel at 0.5, 1, 2, 4, 8, and 24 hours after loading and at 6 weeks ( P 50% IPA (98% versus 31%, P 70% IPA (90% versus 16%, P P P =NS). IPA for ticagrelor on day 3 after the last dose was comparable to clopidogrel at day 5; IPA on day 5 for ticagrelor was similar to clopidogrel on day 7 and did not differ from placebo ( P =NS). Conclusions— Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel; this was sustained during the maintenance phase and was faster in offset after drug discontinuation. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00528411.