SOD2 Gene Variants (rs4880 and rs5746136) and Their Association with Breast Cancer Risk.

The superoxide dismutase (SOD) is the principal antioxidant defense system in the body that is activated by a reactive oxygen species. Some variants of the SOD2 gene have been associated with cancer. The rs4880 variant was determined by PCR real-time and the rs5746136 variant by PCR-RFLP in healthy subjects and in breast cancer (BC) patients. The rs4880 and rs5746136 variants were associated with BC susceptibility when BC patients and the control group were compared for the CT, TT, CTCC, and the T alleles (p < 0.05). The CT genotype of the rs4880 variant showed significant statistical differences in patients and controls aged ≤ 45 years old, and with hormonal consumption (p < 0.05). The rs4880 variant was associated with BC patients with CTTT genotype and obesity, the presence of DM2-SAH, and a non-chemotherapy response (p < 0.05). Additionally, the rs5746136 variant was associated with susceptibility to BC with Ki-67 (≥20%), luminal A type BC, and a chemotherapy partial response (p < 0.05) in BC patients who carry TT, TC, and CTTT genotypes, respectively. The haplotype T/T (OR 1.98; 95% CI 1.20−3.26, p = 0.005) was observed to be a risk factor for BC. The rs4880 and rs5746136 variants in the SOD2 gene were associated with BC susceptibility.

GC/MS Analysis, Antioxidant Activity, and Antimicrobial Effect of Pelargonium peltatum (Geraniaceae).

In recent years, the increase in antibiotic resistance demands searching for new compounds with antimicrobial activity. Phytochemicals found in plants offer an alternative to this problem. The genus Pelargonium contains several species; some have commercial use in traditional medicine such as P. sinoides, and others such as P. peltatum are little studied but have promising potential for various applications such as phytopharmaceuticals. In this work, we characterized the freeze-dried extracts (FDEs) of five tissues (root, stem, leaf, and two types of flowers) and the ethyl acetate fractions from leaf (Lf-EtOAc) and flower (Fwr-EtOAc) of P. peltatum through the analysis by thin-layer chromatography (T.L.C.), gas chromatography coupled to mass spectrometry (GC-MS), phytochemicals quantification, antioxidant capacity, and antimicrobial activity. After the first round of analysis, it was observed that the FDE-Leaf and FDE-Flower showed higher antioxidant and antimicrobial activities compared to the other FDEs, for which FDE-Leaf and FDE-Flower were fractionated and analyzed in a second round. The antioxidant activity determined by ABTS showed that Lf-EtOAc and Fwr-EtOAc had the lowest IC50 values with 27.15 ± 1.04 and 28.11 ± 1.3 µg/mL, respectively. The content of total polyphenols was 264.57 ± 7.73 for Lf-EtOAc and 105.39 ± 4.04 mg G.A./g FDE for Fwr-EtOAc. Regarding the content of flavonoid, Lf-EtOAc and Fw-EtOAc had the highest concentration with 34.4 ± 1.06 and 29.45 ± 1.09 mg Q.E./g FDE. In addition, the minimum inhibitory concentration (M.I.C.) of antimicrobial activity was evaluated: Lf-EtOAc and Fwr-EtOAc were effective at 31.2 µg/mL for Staphylococcus aureus and 62.5 µg/mL for Salmonella enterica, while for the Enterococcus feacalis strain, Fwr-EtOAc presented 31.2 µg/mL of M.I.C. According to the GC-MS analysis, the main compounds were 1,2,3-Benzenetriol (Pyrogallol), with 77.38% of relative abundance in the Lf-EtOAc and 71.24% in the Fwr-EtOAc, followed by ethyl gallate (13.10%) in the Fwr-EtOAc and (Z)-9-Octadecenamide (13.63% and 6.75%) in both Lf-EtOAc and Fwr-EtOAc, respectively.

Medical Marijuana, Recreational Cannabis, and Cardiovascular Health: A Scientific Statement From the American Heart Association.

Cannabis, or marijuana, has potential therapeutic and medicinal properties related to multiple compounds, particularly Δ-9-tetrahydrocannabinol and cannabidiol. Over the past 25 years, attitudes toward cannabis have evolved rapidly, with expanding legalization of medical and recreational use at the state level in the United States and recreational use nationally in Canada and Uruguay. As a result, the consumption of cannabis products is increasing considerably, particularly among youth. Our understanding of the safety and efficacy of cannabis has been limited by decades of worldwide illegality and continues to be limited in the United States by the ongoing classification of cannabis as a Schedule 1 controlled substance. These shifts in cannabis use require clinicians to understand conflicting laws, health implications, and therapeutic possibilities. Cannabis may have therapeutic benefits, but few are cardiovascular in nature. Conversely, many of the concerning health implications of cannabis include cardiovascular diseases, although they may be mediated by mechanisms of delivery. This statement critically reviews the use of medicinal and recreational cannabis from a clinical but also a policy and public health perspective by evaluating its safety and efficacy profile, particularly in relationship to cardiovascular health.

The American Heart Association 2030 Impact Goal: A Presidential Advisory From the American Heart Association.

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.

Association of peripheral artery disease with in-hospital outcomes after endovascular transcatheter aortic valve replacement.

OBJECTIVES: The aim of this study was to determine the prevalence of peripheral artery disease (PAD) and its association with in-hospital outcomes after endovascular transcatheter aortic valve replacement (EV-TAVR). BACKGROUND: TAVR is an established treatment for patients at prohibitive, high, or intermediate surgical risk. PAD is a significant comorbidity in the determination of surgical risk. However, data on association of PAD with outcomes after EV-TAVR are limited. METHODS: Patients in the National Inpatient Sample who underwent EV-TAVR between January 1, 2012 and September 30, 2015 were evaluated. The primary outcome was in-hospital mortality. RESULTS: A total of 51,685 patients underwent EV-TAVR during the study period. Of these, 12,740 (24.6%) had a coexisting diagnosis of PAD. The adjusted odds for in-hospital mortality [OR 1.08 (95% CI 0.83-1.41)], permanent pacemaker implantation [OR 0.98 (0.85-1.14)], conversion to open aortic valve replacement [OR 1.05 (0.49-2.26)], or acute myocardial infarction [OR 1.31(0.99-1.71)] were not different in patients with versus without PAD. However, patients with PAD had greater adjusted odds of vascular complications [OR 1.80 (1.50-2.16)], major bleeding [OR 1.20 (1.09-1.34)], acute kidney injury (AKI) [OR 1.19 (1.05-1.36)], cardiac complications [aOR 1.21 (1.01-1.44)], and stroke [OR 1.39(1.10-1.75)] compared with patients without PAD. Length of stay (LOS) was significantly longer for patients with PAD [7.23 (0.14) days vs. 7.11 (0.1) days, p < 0.001]. CONCLUSION: Of patients undergoing EV-TAVR, ~25% have coexisting PAD. PAD was not associated with increased risk of in-hospital mortality but was associated with higher risk of vascular complications, major bleeding, AKI, stroke, cardiac complications, and longer LOS.

Non-eligibility for reperfusion therapy in patients presenting with ST-segment elevation myocardial infarction: Contemporary insights from the National Cardiovascular Data Registry (NCDR).

BACKGROUND: Reperfusion therapy is lifesaving in patients presenting with ST-segment elevation myocardial infarction (STEMI). Contemporary data describing the characteristics and outcomes of patients presenting with STEMI not receiving reperfusion therapy are lacking. METHODS: Using the ACTION Registry-GWTG database, we examined 219,726 STEMI patients (January 2007-December 2013) at 721 percutaneous coronary intervention (PCI)-capable hospitals in United States. Clinical characteristics and in-hospital outcomes were stratified by those who underwent reperfusion (n = 188,200; 86%), those who did not undergo reperfusion with a reason for ineligibility (n = 27,179; 12%), and those without reperfusion but had no reason for ineligibility (n = 4,347; 2%). RESULTS: Compared with STEMI patients receiving reperfusion therapy, the nonreperfusion groups were older, were more often female, and had higher rates of hypertension, diabetes, prior myocardial infarction, prior stroke, atrial fibrillation, and left bundle-branch block and heart failure on presentation. The major reason for reperfusion noneligibility was coronary anatomy not suitable for PCI (33%). Presence of 3-vessel coronary disease was more common in the nonreperfusion groups (with or without a documented reason) compared with reperfusion group (38% and 36% vs 26%, P < .001, respectively). In-hospital mortality was higher in patients not receiving reperfusion therapy with or without a documented reason compared with the reperfusion group (adjusted odds ratio [95% CI] 1.88 [1.78-1.99] and 1.37 [1.21-1.57], respectively). CONCLUSION: Most patients with STEMI not receiving reperfusion therapy had a documented reason. Coronary anatomy not suitable for PCI was the major contributor to ineligibility. In-hospital mortality was higher in patients not receiving reperfusion therapy.

[Impact of concomitant use of P2Y12 inhibitors and proton pump inhibitors on ischemia events in patients with acute coronary syndrome in real world].

Objective: The study aimed to analyze the impact of concomitant administration of P2Y12 inhibitors and PPIs on ischemia events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed data from a international, multi-center registry between 2003 and 2014 in patients with ACS after PCI, grouped the cohort into patients receiving PPIs or no PPIs and assessed 1-year clinical endpoint (all-cause death/re-infarction). Meanwhile, we grouped the cohort into patients receiving clopidogrel or ticagrelor, and compared the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year clinical endpoint. Results: Of 9 429 patients in the final cohort, 54.8% (n=5 165) was prescribed a PPI at discharge. Patients receiving a PPI were more likely to have comorbidities. No association was observed between PPI use and the clinical endpoint (HR 1.00, 95% CI 0.86-1.18). Meanwhile, no association was found between PPI use and the clinical endpoint in patients receiving either clopidogrel or ticagrelor. And the clinical endpoint in patients administrated of clopidogrel and PPIs had no difference with that of ticagrelor and PPIs. Conclusions: In patients with ACS following PCI, increased risk of ischemia event was not found in the concomitant use of PPIs and P2Y12 inhibitors, and especially, compared with ticagrelor, clopidogrel was found no association with ischemia events when concomitant administrated with PPIs.

Clinical characteristics and in hospital outcomes of heart transplant recipients with allograft vasculopathy undergoing percutaneous coronary intervention: Insights from the National Cardiovascular Data Registry.

BACKGROUND: Cardiac allograft vasculopathy is a major cause of morbidity and mortality following heart transplantation. Large multicenter studies evaluating the clinical characteristics and inhospital outcomes of heart transplant recipients undergoing percutaneous coronary intervention (PCI) are lacking. OBJECTIVE: To evaluate the clinical characteristics, treatment patterns and inhospital outcomes of heart transplant recipients undergoing PCI compared to general population. METHODS: We analyzed 1,897,328 patients from the National Cardiovascular Data Registry CathPCI registry who underwent PCI of at least 1 native vessel between July 2009 and December 2013 from 1,477 centers, of which 542 patients (0.03%) were heart transplant recipients. Clinical characteristics were evaluated and, after 1:4 propensity matching, inhospital outcomes were compared between 538 heart transplant patients and 2,128 non-transplant patients. RESULTS: Transplant recipients undergoing PCI had a higher prevalence of diabetes, dyslipidemia and peripheral vascular disease; lower prevalence of angina, acute coronary syndrome, abnormal noninvasive functional study, and type C coronary lesions compared to the non-transplant PCI population. After propensity matching, all-cause inhospital mortality was similar between transplant and non-transplant groups (1.3% vs 1.0%; OR, 1.21; 95% CI, 0.54-2.67). CONCLUSION: This is the largest series to date outlining the characteristics of heart transplant recipients undergoing PCI. Similar inhospital outcomes were noted in heart transplant recipients compared to the general population. Further studies evaluating long-term outcomes are warranted.

Endovascular repair of traumatic aortic injury: a novel arena in interventional cardiology.

OBJECTIVE: To assess the feasibility of endovascular repair of traumatic aortic injuries performed by interventional cardiologists in collaboration with cardiothoracic surgeons. BACKGROUND: Traumatic aortic injury (TAI) represents a significant cause of mortality in trauma patients. Endovascular techniques have recently come into play for the management of TAI and are usually performed by a multidisciplinary team consisting of a thoracic or vascular surgeon and/or interventional radiology. With extensive expertise in catheter-based interventions, interventional cardiologists may have a pivotal role in this important procedure. METHODS: From January 2009 to July 2011, we reviewed the TAI endovascular repair outcomes performed by a team of interventional cardiologists in collaboration with cardiothoracic surgery at our institution. The charts of these patients were reviewed to collect desired data, which included preoperative, procedural, and follow-up details. RESULTS: Twenty patients were identified in our series. Most of these patients developed TAI from motor vehicle accidents. Technical success for endovascular repair of TAI was achieved in all patients. Two patients developed endoleak, of which one patient required subsequent open repair. Two patients expired in the hospital from coexistent injuries. CONCLUSIONS: Our series of endovascular repair for TAI performed by interventional cardiologists with the collaboration of cardiothoracic surgeons showed excellent outcomes. Our experience may give further insight in the collaborative role of interventional cardiology and cardiothoracic surgery for endovascular repair of TAI.

ED administration of thienopyridines in non-ST-segment elevation myocardial infarction: results from the NCDR.

OBJECTIVE: American Heart Association/American College of Cardiology guidelines recommend that patients with definite unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) receive dual antiplatelet therapy on presentation to the hospital when undergoing early invasive management or "as soon as possible" after admission when being managed conservatively. The guidelines do not specify whether these medications should be administered in the emergency department (ED). Our aim was to determine whether ED administration of a thienopyridine was associated with clinical outcomes among patients with NSTEMI. METHODS: We examined thienopyridine use in 39454 patients with NSTEMI who received a thienopyridine within 24 hours of presentation in the National Cardiovascular Data Registry's Acute Coronary Treatment and Intervention Outcomes Network-Get With The Guidelines Registry from January 2007 to June 2010. Patients who were not seen initially in the ED, were transferred in, or were missing time data were excluded. We analyzed the association between ED administration of thienopyridines and outcomes and patient demographics. RESULTS: Of the cohort receiving a thienopyridine within 24 hours, 9534 (24.2%) received it in the ED. Emergency department administration of a thienopyridine was not associated with in-hospital major bleeding (multivariable adjusted odds ratio, 0.99; 95% confidence interval, 0.91-1.09) or in-hospital mortality (adjusted 1.02; 95% confidence interval, 0.86-1.20). Independent predictors most strongly associated with ED thienopyridine administration were elevated troponin, ED length of stay, prior percutaneous coronary intervention, and initial electrocardiogram showing ischemic changes. CONCLUSIONS: There was no association between ED thienopyridine administration and in-hospital major bleeding or mortality. Emergency department length of stay, electrocardiographic changes, and elevated troponin were associated with ED thienopyridine administration.

Intron 4 VNTR (4a/b) polymorphism of the endothelial nitric oxide synthase gene is associated with breast cancer in Mexican women.

The endothelial nitric oxide synthase (eNOS) gene plays an important role in several biological functions. Polymorphisms of the eNOS gene have been associated with cancer. It has been suggested that the VNTR 4 a/b polymorphism may affect the expression of eNOS and contributes to tumor promotion in the mammary gland. We examined the role of the eNOS4 a/b polymorphism by comparing the genotypes of 281 healthy Mexican women with the genotypes of 429 Mexican women with breast cancer (BC). The observed genotype frequencies for control and BC patients were 0.6% and 0.7% for a/a (polymorphic); 87% and 77% for a/a (wild type); and 12% and 22% for a/b respectively. We found that the odds ratio (OR) was 1.9, with a 95% confidence interval (95%CI) of 1.29-2.95, P = 0.001 for genotypes a/a-a/b, b/c. The association was also evident when comparing the distribution of the a/a-a/b genotypes in patients with high levels of glutamate-oxaloacetate transaminase (SGOT) (OR, 1.93; 95% CI, 1.14-3.28; P = 0.015); undergoing menopause with high levels of SGOT (OR, 2.0; 95% CI, 1.1-3.84); and with high levels of glutamic-pyruvic transaminase (SGPT) (OR, 3.5; 95% CI, 1.56-8.22). The genotypes a/a-a/b are associated with BC susceptibility in the analyzed samples from the Mexican population.

Optimal medical therapy improves outcomes in patients with diabetes mellitus and acute myocardial infarction.

AIMS: We aimed to explored the association between the use of optimal medical therapy (OMT) in patients with myocardial infarction (AMI) and diabetes mellitus (DM) and clinical outcomes. METHODS: Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) is an international registry that enrolled participants with acute coronary syndrome followed up for at least 1 year across 15 centers from 2003 to 2014. Baseline characteristics and endpoints were analyzed. RESULTS: Among 3095 (23.2%) patients with AMI and DM, 1898 (61.3%) received OMT at hospital discharge. OMT was associated with significantly reduced mortality (4.3% vs. 10.8%, p < 0.001), re-AMI (4.4% vs. 8.1%, p < 0.001), and composite endpoint of death/re-AMI (8.0% vs. 17.6%, p < 0.001). No difference was observed among regions. Propensity score matching confirmed that OMT significantly associated with lower mortality. After adjusting for confounding variables, OMT, drug-eluting stents, and complete revascularization were independent protective factors of 1-year mortality, whereas left ventricular ejection fraction and age were risk factors. CONCLUSIONS: Guideline-recommended OMT was prescribed at suboptimal frequencies with geographic variations in this worldwide cohort. OMT can improve long-term clinical outcomes in patients with DM and AMI. CLINICAL TRIAL REGISTRATION: NCT02466854 June 9, 2015.

Use of emergency medical service transport among patients with ST-segment-elevation myocardial infarction: findings from the National Cardiovascular Data Registry Acute Coronary Treatment Intervention Outcomes Network Registry-Get With The Guidelines.

BACKGROUND: Activation of emergency medical services (EMS) is critical for the early triage and treatment of patients experiencing ST-segment-elevation myocardial infarction, yet data regarding EMS use and its association with subsequent clinical care are limited. METHODS AND RESULTS: We performed an observational analysis of 37 634 ST-segment-elevation myocardial infarction patients treated at 372 US hospitals participating in the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines between January 2007 and September 2009, and examined independent patient factors associated with EMS transportation versus patient self-transportation. We found that EMS transport was used in only 60% of ST-segment-elevation myocardial infarction patients. Older patients, those living farther from the hospital, and those with hemodynamic compromise were more likely to use EMS transport. In contrast, race, income, and education level did not appear to be associated with the mode of transport. Compared with self-transported patients, EMS-transported patients had significantly shorter delays in both symptom-onset-to-arrival time (median, 89 versus 120 minutes; P<0.0001) and door-to-reperfusion time (median door-to-balloon time, 63 versus 76 minutes; P<0.0001; median door-to-needle time, 23 versus 29 minutes; P<0.0001). CONCLUSIONS: Emergency medical services transportation to the hospital is underused among contemporary ST-segment-elevation myocardial infarction patients. Nevertheless, use of EMS transportation is associated with substantial reductions in ischemic time and treatment delays. Community education efforts are needed to improve the use of emergency transport as part of system-wide strategies to improve ST-segment-elevation myocardial infarction reperfusion care.

Characteristics and in-hospital outcomes of patients presenting with non-ST-segment elevation myocardial infarction found to have significant coronary artery disease on coronary angiography and managed medically: stratification according to renal function.

BACKGROUND: The characteristics, therapies, and outcomes of patients presenting with non-ST-segment elevation myocardial infarction, found to have significant coronary artery disease on coronary angiography, and managed without revascularization ("nonrevascularized patients") have not been evaluated previously in a large-scale registry. METHODS: We examined data on 13,872 non-ST-segment elevation myocardial infarction nonrevascularized patients who were captured by the Acute Coronary Treatment and Intervention Outcomes Network registry. Patients were divided according to baseline renal function in 4 groups: no chronic kidney disease (CKD) and CKD stages 3, 4, and 5. RESULTS: The in-hospital mortality of nonrevascularized patients was 3.7%, whereas their in-hospital major bleeding rate was 10.8%. Overall, 44.2% (n = 6,132) of nonrevascularized patients had CKD. Compared with patients with normal renal function, nonrevascularized patients with CKD had significantly more history of myocardial infarction, heart failure, more 3-vessel coronary artery disease, and received fewer antithrombotic therapies. In addition, they had significantly higher rates of in-hospital mortality and major bleeding; CKD stage 4 was associated with the highest risk of adverse events. The multivariable-adjusted odds ratios of in-hospital mortality for CKD stages 3, 4, and 5 relative to no CKD were 1.5, 2.5, and 2.2, respectively (global P < .0001), and the analogous adjusted odds ratios of major bleeding were 1.5, 2.5, and 1.8 (global P < .0001). CONCLUSION: Nonrevascularized patients have a high in-hospital mortality. Nonrevascularized patients with CKD have more comorbidities than patients without CKD and less frequently receive guideline-recommended therapies. Chronic kidney disease is strongly associated with in-hospital mortality and bleeding.

Limitations of using cardiac catheterization rates to assess the quality of care for patients with non-ST-segment elevation myocardial infarction.

BACKGROUND: An early invasive management strategy is recommended for patients with non-ST-segment elevation myocardial infarction (NSTEMI) who do not have a contraindication to cardiac catheterization (CCC). However, the frequency of CCC reporting has not been delineated, and the relationship of CCC reporting to hospital-level guidelines adherence for NSTEMI has not been investigated. METHODS: We used the American College of Cardiology National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines database to evaluate variations in hospital-level reporting of CCC for 111,320 patients with NSTEMI admitted to 370 hospitals with revascularization capabilities in the United States from 2007 to 2010 and how these variations were associated with guideline adherence and in-hospital mortality. Hospitals were grouped into tertiles based on rates of reported CCCs. Treatment patterns and in-hospital mortality rates were evaluated across hospital tertiles separately for patients with and without a reported CCC. RESULTS: A total of 18,290 (16.4%) of 111,320 patients with NSTEMI had a reported CCC, but hospital-level CCC reporting varied considerably (low tertile 0%-8.2%, intermediate tertile >8.2%-18.8%, and high tertile >18.8%-75.6%). Patients with a reported CCC had more comorbidities and high-risk features compared with patients without a CCC. The use of most guideline-recommended medications and in-hospital mortality rates were similar across hospital tertiles-both for patients with and without a reported CCC. CONCLUSIONS: The reporting of CCC among patients with NSTEMI varies widely across US hospitals and does not appear to be related to guidelines adherence or in-hospital mortality rates. These findings suggest that it will be a challenge to standardize the reporting of CCC and thus use invasive management to assess the quality of NSTEMI care.

In-hospital and 1-year outcomes with drug-eluting versus bare metal stents in saphenous vein graft intervention: a report from the EVENT registry.

OBJECTIVES: To compare outcomes of patients receiving drug-eluting stents (DES) versus bare metal stents (BMS) during percutaneous coronary intervention (PCI) of saphenous vein bypass grafts (SVG). BACKGROUND: Long-term benefits of DES versus BMS are well established for native vessel PCI. Benefit in patients undergoing SVG intervention is less certain. We used data from a multicenter registry (evaluation of drug eluting stents and ischemic events, EVENT) to compare outcomes among patients treated with DES versus BMS 1-year following SVG interventions. METHODS: Between July 2004 and December 2007, 684 patients in EVENT underwent SVG PCI (515 DES only, 169 BMS only). The primary endpoint was a composite of death, myocardial infarction (MI), and target lesion revascularization between hospital discharge and 1-year follow-up. Propensity score stratification was used to adjust for differences between groups. RESULTS: Baseline demographic and clinical characteristics of patients treated with DES and BMS were similar. The DES group had fewer men and a higher prevalence of prior PCI. Patients receiving DES had less angiographic thrombus, less frequent use of embolic protection devices, greater total stent length, and smaller maximum stent diameters. Unadjusted outcomes between discharge and 1-year follow-up did not differ between the groups. After risk adjustment, the primary outcome was less frequent among patients treated with DES (adjusted HR = 0.48, 95% CI = 0.27-0.84, P < 0.01) with similar relative benefits across the individual endpoints. CONCLUSIONS: Among patients undergoing SVG PCI in a "real world" registry analyzed using propensity score stratification, treatment with DES compared with BMS was associated with reduced MACE at 1 year following PCI.

Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials.

Cangrelor is an intravenous antagonist of the P2Y(12) receptor characterized by rapid, potent, predictable, and reversible platelet inhibition. However, cangrelor was not superior to clopidogrel in reducing the incidence of ischemic events in the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. A prospectively designed platelet function substudy was performed in a selected cohort of patients to provide insight into the pharmacodynamic effects of cangrelor, particularly in regard to whether cangrelor therapy may interfere with the inhibitory effects of clopidogrel. This pre-defined substudy was conducted in a subset of patients from the CHAMPION-PCI trial (n = 230) comparing cangrelor with 600 mg of clopidogrel administered before percutaneous coronary intervention (PCI) and from the CHAMPION-PLATFORM trial (n = 4) comparing cangrelor at the time of PCI and 600 mg clopidogrel given after the PCI. Pharmacodynamic measures included P2Y12 reaction units (PRU) assessed by VerifyNow P2Y12 testing (primary endpoint marker), platelet aggregation by light transmittance aggregometry following 5 and 20 µmol/L adenosine diphosphate stimuli, and markers of platelet activation determined by flow cytometry. The primary endpoint was the percentage of patients who achieved <20 % change in PRU between baseline and >10 h after PCI. The main trial was stopped early limiting enrollment in the platelet substudy. A total of 167 patients had valid pharmacodynamic assessments for the primary endpoint. The percent of individuals achieving <20 % change in PRU between baseline and >10 h after PCI was higher with cangrelor + clopidogrel (32/84, 38.1 %) compared with placebo + clopidogrel (21/83, 25.3 %), but this was not statistically significant (difference:12.79 %, 95 % CI: -1.18 %, 26.77 %;p = 0.076). All pharmacodynamic markers as well as the prevalence of patients with high on-treatment platelet reactivity were significantly lower in patients treated with cangrelor. A rapid platelet inhibitory effect was achieved during cangrelor infusion and a rapid offset of action after treatment discontinuation. This CHAMPION platelet function substudy represents the largest pharmacodynamic experience with cangrelor, demonstrating its potent P2Y(12) receptor inhibitory effects, and rapid onset/offset of action. Although there was no significant pharmacodynamic interaction when transitioning to clopidogrel therapy, further studies are warranted given that enrollment in this study was limited due to premature interruption of the main trial.

A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial.

AIMS: Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM. METHODS AND RESULTS: Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospective, randomized, double-blind, crossover study in patients with type 2 DM and coronary artery disease (CAD). Patients (n= 35) were randomly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period. Platelet function was assessed by VerifyNow® P2Y12 assay, light transmission aggregometry, and vasodilator-stimulated phosphoprotein phosphorylation at 0, 1, 4, and 24 h and 7 days. Greater platelet inhibition by VerifyNow® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD (least squares mean, 89.3 vs. 27.7%, P< 0.0001; primary endpoint). The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days (P < 0.0001). Similar results were obtained using all other platelet function measures. Prasugrel resulted in fewer poor responders at all time points irrespective of definition used. CONCLUSION: In patients with type 2 DM and CAD, standard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel.

Mild haemoglobin drop and clinical outcomes in acute coronary syndrome patients: finding from the BleeMACS registry.

BACKGROUND: Haemoglobin drop is common in acute coronary syndrome (ACS) patients and correlates with poor prognosis. However, the association between mild haemoglobin drop and adverse clinical outcome remains insufficiently investigated. This study aimed to examine the association between in-hospital haemoglobin drop and risk for adverse clinical outcomes in ACS patients, especially those with mild drop. METHODS: Included patients from the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) registry were categorized into three groups by the presence and amount of in-hospital haemoglobin drop (non-drop, mild drop and severe drop). The cut-off point between mild drop and severe drop is ≥ 3 g/dL. Multivariate Cox regression was used to assess the association between haemoglobin drop and major adverse cardiac endpoints (MACE). Patients taking potent P2Y12 inhibitors were selected for the additional analysis. Propensity score matching was used to avoid selective bias in the additional analysis. RESULTS: Of 6911 patients, 4949 patients (71.6%) experienced in-hospital haemoglobin drop. Compare with non-drop group, patients with haemoglobin drop had higher risk of MACE [adjusted hazard ratio (HR) = 1.36, 95% CI: 1.03-1.80 for mild drop group; adjusted HR = 1.70, 95% CI: 1.07-2.68 for severe drop group]. Patients in mild drop group were less likely to receive potent P2Y12 inhibitors at discharge (mild drop group vs. severe drop group vs. non-drop group: 10.9% vs. 10.7% vs. 23.8%). After propensity score matching adjustment among patients with potent P2Y12 inhibitors, patients in mild drop group were not associated with an increased risk of MACE than those in non-drop group (adjusted HR = 1.52, 95% CI: 0.49-4.72). CONCLUSIONS: In-hospital haemoglobin drop was common in ACS patients and associated with a higher risk for adverse events. Reduced prescription for potent P2Y12 inhibitors may be responsible for poor prognoses among patients with mild haemoglobin drop.