Lower Cardiovascular Events Research Articles

Coronary artery bypass graft surgery with bilateral internal mammary artery. Medium-term results.

Coronary artery bypass graft (CABG) surgery is one of the main strategies in the treatment of coronary heart disease. The benefit of using the left internal mammary artery (IMA) to revascularize the anterior descending artery is greatly demonstrated, improving long-term survival in patients receiving this graft. On the other hand there are variable currents about the use of two internal mammary arteries, although several studies have already demonstrated the superiority of the use of two mammary arteries over one. Retrospective study of Coronary artery bypass graft surgeries with bilateral mammary artery, performed at Instituto Nacional Cardiovascular - INCOR EsSalud between January 2012 and June 2018. The objective was to determine the mortality rate and major adverse cardiovascular events in a medium term follow-up of 30 months. 121 patients were operated with bilateral internal mammary artery. All patients underwent dissection of mammary artery with skeletonized technique. There was one in-hospital death due to mediastinitis. Major adverse cardiovascular events occurred in 5.8% of patients (death 0.8%, stroke 0%, perioperative myocardial infarction 1.6%, need for new coronary intervention 3.3%). The incidence of mediastinitis and/or sternal reconstruction was 0.8%. : CABG with bilateral IMA is a safe procedure, with low mortality rates and low major adverse cardiovascular events in a 30-month follow-up.

Abstract 344: Low Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events After Percutaneous Coronary Intervention

Introduction: Lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk of major adverse cardiovascular events (MACE). Few studies have examined LDL-C control and outcomes exclusively after percutaneous coronary intervention (PCI). Furthermore, guidelines provide no formal recommendation on when to check LDL-C after PCI. It is therefore conceivable that LDL-C is not routinely measured after PCI, many patients may have elevated LDL-C levels (≥ 70mg/dL), and that elevated LDL-C levels after PCI are associated with adverse long-term outcomes. Objective: To evaluate LDL-C levels after PCI procedures, and to assess the association between LDL-C and cardiovascular events in a population-based cohort. Methods: All patients who received their first PCI between Oct 2011 and Sep 2014 in Ontario, Canada, and had a cholesterol measurement within 6 months after PCI were included. Multivariable Fine and Gray sub-distribution hazards models were used to assess the association between LDL-C measured after PCI and the incidence of MACE (myocardial infarction, coronary revascularization, stroke and cardiovascular death) through December 31, 2016. Results: There were 47,884 patients who had their first PCI during the study period, and 52% had an LDL-C measurement within 6 months post-procedure (median age 63 years, 27% female). Among them, 57% had LDL-C < 70mg/dL, 28% had LDL-C 70 to < 100mg/dL, and 15% had LDL-C ≥ 100mg/dL. After a median of 3.2 years of follow-up, 19% of patients had a qualifying MACE. After adjustment, the incidence of MACE was significantly higher in patients with higher LDL-C levels (Figure). Conclusions: Only one in two patients had LDL-C measured within 6 months after undergoing PCI and only about half had LDL-C < 70mg/dL. Higher levels of LDL-C after PCI were associated with a significantly higher incidence of MACE. Recommendations for routine LDL-C assessment and optimization may improve patient outcomes after PCI procedures.

The sweet spot: fasting glucose, cardiovascular disease, and mortality in older adults with diabetes: a nationwide population-based study

BackgroundGrowing evidences shows that fasting glucose target should be different according to their health condition in older adults with diabetes. However, there are limited data regarding the relationship between fasting glucose level and health outcomes in Korean older people with diabetes. We aimed to examine the association of fasting glucose with mortality and cardiovascular events in Korean older adults with type 2 diabetes.MethodsFrom the Korean National Health Insurance System, 227,938 subjects (aged ≥ 65 years) with type 2 diabetes but no history of cardiovascular events (myocardial infarction or stroke) who underwent ≥ 2 health examinations from 2009 to 2010 and who were followed up until 2017 were identified. The primary exposure variable was the mean fasting glucose level. We estimated the relationship between the baseline fasting glucose level and incidences of all-cause death and cardiovascular events. Comorbidity load was assessed using the Charlson comorbidity index.ResultsFasting glucose levels and all-cause mortality risk showed a J-shaped relationship regardless of sex and number of comorbidities. Fasting glucose levels associated with the lowest mortality and cardiovascular events were 110–124 and 95–124 mg/dL, respectively. Stratified analysis by comorbidity load using the Charlson comorbidity index revealed higher optimal fasting glucose levels for the lowest cardiovascular events in subjects with Charlson comorbidity index ≥ 3 than in those with Charlson comorbidity index ≤ 2 (119 vs. 112 mg/dL, P = 0.04).ConclusionsJ-shaped relationship existed between fasting glucose and all-cause mortality and cardiovascular events in Korean older adults with diabetes. We identified that fasting glucose levels associated with the lowest mortality and cardiovascular events were 110–124 and 95–124 mg/dL respectively. Increased risk of cardiovascular events with low fasting glucose level (< 95 mg/dL) was noted, especially in patients with high comorbidity. These findings suggested that less stringent targets of fasting glucose may be beneficial especially in older adults with multiple comorbidities.

Low blood pressure and cardiovascular events in diabetic patients with coronary artery disease after revascularization: the CREDO-Kyoto registry cohort-1.

The current American, European, and Japanese guidelines for hypertension treatment have lowered blood pressure (BP) targets to <130/80 mmHg in patients with diabetes mellitus (DM) and patients with coronary artery disease (CAD). However, there is concern that low BP may increase cardiovascular events in diabetic CAD patients. Currently, coronary revascularization has become widespread in diabetic CAD patients. Thus, whether low BP is an independent risk factor for cardiovascular events in diabetic CAD patients after revascularization was investigated. We examined 2718 stable CAD patients with DM in the CREDO-Kyoto cohort-1 registry enrolling 9877 patients who underwent their first percutaneous coronary intervention or coronary bypass grafting. There were no cutoff points for systolic BP (SBP) below which the age- and sex-adjusted hazard ratios for cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke increased. The cutoff diastolic BP (DBP) for increasing cardiovascular death was 70 mmHg (P = 0.014), whereas there was no cutoff DBP for increasing nonfatal MI and nonfatal stroke. However, on stepwise Cox hazard proportional regression analysis, the independent factors increasing cardiovascular death were hypertension, low creatinine clearance, wide pulse pressure, prior MI, and nonuse of statins, but DBP < 70 mmHg was not a significant factor. In conclusion, in diabetic CAD patients after coronary revascularization, low SBP and DBP were not significant factors that increased cardiovascular events. Careful attention should be paid to vascular lesions and organ damage that have already progressed.

Sustained degradation of quality of life in a subgroup of lymphoma survivors: a two-year prospective survey

BackgroundPrevious studies have suggested that lymphoma survivors commonly display altered Health-Related Quality of Life (HRQoL). Because these were predominantly cross-sectional studies, the dynamic of events as well as the factors which influence HRQoL remain to be determined.MethodsWe conducted a prospective study on a cohort of 204 Hodgkin and non-Hodgkin lymphoma survivors who remained disease-free 2 years after undergoing chemotherapy (referred to the M0-M12-M24 periods).ResultsWe found that although Physical and Mental Component Scores (PCS and MCS) of HRQoL significantly improved from M0 to M24 in the vast majority of patients (favorable group), approximately 20% of patients displayed severe alterations in HRQoL (global SF-36 scores < 50) extending over the 2-year period (unfavorable group). Low M24 PCSs were associated with Post-Traumatic Stress Disorder (PTSD), depression, cardiovascular events and neuropathy. In contrast social determinants, comorbidity and infections, as well as several other parameters related to the disease or to the treatment itself were not associated with low M24 PCSs. Low M24 MCSs were associated with a low educational level, aggressive histology, infections, cardiovascular events and PTSS. However, the most predictive risk factor for low SF-36 scores at M24 was a low SF-36 score at M12. The unfavorable group also displayed a low incidence of return to work.ConclusionsAlthough the HRQoL of lymphoma survivors generally improved over time, persistent and severe HRQoL alterations still affected approximately one fifth of patients, resulting in important social consequences. This specific group, which presents with identifiable risk factors, may benefit from early, targeted psycho-social support.

Intravascular Lithotripsy in Calcified Coronary Lesions: A Prospective, Observational, Multicenter Registry.

Optimal plaque preparation of calcified coronary lesions is key to prevent stent failure. The purpose of this study was to determine the strategy success and safety of intravascular lithotripsy (IVL) in calcified lesions of an all-comers cohort. Patients with calcified coronary lesions were screened in 3 centers. Seventy-one patients were eligible for IVL. Patients were assigned to (group A) primary IVL therapy for patients with calcified de-novo lesions (n=39 lesions), (group B) secondary IVL therapy for patients with calcified lesions in which noncompliant balloon dilatation failed (n=22 lesions), and (group C) tertiary IVL therapy in patients with stent underexpansion after previous stenting (n=17 lesions). Primary end point was strategy success (stent expansion with <20% in-stent residual stenosis) and safety outcomes (procedural complications, in-hospital major adverse cardiovascular event). Seventy-eight calcified lesions were treated using the Shockwave C2 balloon. Mean diameter stenosis of calcified lesions was 71.8±13.1% at baseline, decreased to 45.1±17.4% immediately after IVL, and to 17.5±15.2% after stenting. Mean minimal lumen diameter was 1.01±0.49 mm at baseline and increased to 1.90±0.61 after IVL, and to 2.88±0.56 mm after stenting. The primary end point of strategy success was reached in 84.6% (group A), 77.3% (group B), and 64.7% (group C). Device delivery and IVL treatment were possible in all lesions. Four type b dissections were observed without further sequelae. No patient suffered from in-hospital major adverse cardiovascular event. Seven Shockwave balloons ruptured during treatment without any sequelae. IVL provides a valid strategy for lesion preparation in severely calcified coronary lesions with high success rate, low procedural complications, and low major adverse cardiovascular event rates.

Risk factors and clinical outcomes in chronic coronary and peripheral artery disease: An analysis of the randomized, double-blind COMPASS trial.

Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8-2.6) and cardiovascular death (hazard ratio 2.0; 1.5-2.7) were more than twofold higher in patients with 4-6 compared with 0-1 risk factors (p < 0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors (p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.

Low total cholesterol is associated with increased major adverse cardiovascular events in men aged ≥70 years not taking statins

ObjectiveLow levels of total cholesterol (TC) are associated with adverse outcomes in older populations. Whether this phenomenon is independent of statin use is unknown. We investigated the association between low...

Medical adjunctive therapy for patients with chronic limb-threatening ischemia: a systematic review.

The aim of this article is to systematically review the literature on medical adjunctive therapy for patients with chronic limb-threatening ischemia (CLTI). MEDLINE, Embase, and Cochrane Database of Systematic Reviews were searched for studies published between January 1st, 2009, and June 1st, 2019. Articles that studied medical treatment of CLTI patients and reported clinical outcomes were eligible. Main exclusion criteria were case reports <20 patients, incorrect publication type, and CLTI caused by Buerger disease. The primary end point was major amputation (above the ankle) in studies with a follow-up of ≥6 months. Secondary end points were other clinical end points such as death and wound healing. Study quality was assessed according to the Downs and Black checklist. Included were 42 articles: four focused on antiplatelet therapy, five on antihypertensive medication, 6 on lipid-lowering therapy, 16 on stem cell therapy, three on growth factors, five on prostanoids, and one study each on cilostazol, glucose-lowering therapy, spinal cord stimulation, sulodexide, and hemodilution. Calcium channel blockers, iloprost, cilostazol, and hemodilution showed significant improvement of limb salvage, but data are limited. Stem cell therapy showed no significant improvement of limb salvage but could potentially improve wound healing. Antiplatelets, antihypertensives, and statins showed significantly lower cardiovascular events rates but not evident lower major amputation rates. The quality of the studies was fair to good. Certain medical therapies serve to improve limb salvage next to revascularization in CLTI patients, whereas others are important in secondary prevention. Because high quality evidence is limited, further research is needed.

P6204Oral vaccination of Lactococcus lactis expressing Ling Zhi 8 protein prevents nonalcoholic fatty liver and early atherogenesis in cholesterol-fed rabbits

Abstract Background Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis. Epidemiology studies have indicated that NAFLD may be an independent risk factor for atherosclerosis. Anti-inflammation therapy by inhibiting IL-1β led to a significantly lower cardiovascular event rate in recent clinical trial (CANTOS trial). Ling Zhi 8 (LZ8) is an immunomodulatory protein that possesses a broad range of pharmacological properties, including anti-inflammatory activities. Methods and findings In this study, we developed an oral vaccination of Lactococcus lactis expressing LZ8 protein in a nisin-controlled gene expression system and investigated its anti-inflammation properties. Experimental rabbits received commercial rabbit chow supplemented with 2% cholesterol for 5 weeks and recombinant LZ8 L. lactis vaccine once a day on weekdays. The expression of IL-1β in the aorta (Figure A) was significantly suppressed after LZ8 vaccination. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the sub-endothelial space (Figure C). LZ8 also inhibited the expression of IL-1β in the liver (Figure B), decreased fat droplet deposits and infiltration of inflammatory cells (Figure D), and improved liver function by decreasing liver enzymes. Figure 1 Conclusions Our results suggest that LZ8 could be used as a therapeutic tool to improve both atherosclerosis and NAFLD due to its anti-inflammatory effect. Acknowledgement/Funding TCVGH-1067317C, TCVGH-1063108C

P832LDL-C levels on statins and cardiovascular event risk in stable coronary artery disease: An observation from the REAL-CAD study

Abstract Background The relation between very low on-treatment low-density lipoprotein cholesterol (LDL-C) level and the cardiovascular event risk is still unclear in patients receiving the same doses of statins. Methods From the REAL-CAD study comparing high-dose with low-dose pitavastatin therapy in Japanese patients with stable coronary artery disease, 11105 patients without reported non-adherence for the study drug were divided into 3 groups according to the on-treatment LDL-C level at 6-month (&lt;70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL; N=1016, N=3078, and N=1665 in the pitavastatin 1 mg/day stratum; N=2431, N=2524, and N=391 in the pitavastatin 4 mg/day stratum). Primary outcome measure was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission. Results In the pitavastatin 1 mg/day stratum, cumulative 4-year incidence of the primary outcome measure was not significantly different across the 3 groups (5.0%, 5.7%, and 5.2%, P=0.51), while in the 4 mg/day stratum, it was significantly higher in the LDL-C ≥100 mg/dL group than in other groups (4.5%, 3.4%, and 9.1%, P&lt;0.001). The adjusted risks of the LDL-C &lt;70 mg/dL group relative to the LDL-C 70–100 mg/dL group (reference) remained insignificant for the primary outcome measure in both 1 mg/day and 4 mg/day strata (HR 0.84, 95% CI 0.58–1.18, P=0.32, and HR 1.25, 95% CI 0.88–1.79, P=0.22). The adjusted risk of LDL-C ≥100 mg/dL group relative to the reference group was not significant for the primary outcome measure in the 1 mg/day stratum (HR 0.82, 95% CI 0.60–1.11, P=0.21), while it was highly significant in the 4 mg/day stratum (HR 3.32, 95% CI 2.08–5.17, P&lt;0.001). In the on-treatment LDL-C ≥100 mg/dL group in the 4 mg/day stratum, LDL-C increased by 6.3 mg/dL from baseline to 6-month despite dose escalation of pitavastatin from 1 mg/day to 4 mg/day, suggesting the presence of unreported poor adherence in this small subgroup. Adjusted Effects of On-treatment LDL-C Conclusions Very low on-treatment LDL-C level (&lt;70 mg/dL) was not associated with lower cardiovascular event risk compared with moderately low on-treatment LDL-C level (70–100 mg/dL) in patients receiving the same doses of statins. Too much emphasis on the target LDL-C strategy might mislead the clinical practice. Acknowledgement/Funding The Comprehensive Support Project for Clinical Research of Lifestyle-Related Disease of the Public Health Research Foundation.

Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The EMPA-HEART CardioLink-6 Randomized Clinical Trial.

SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with type 2 diabetes mellitus and coronary artery disease. Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5% to 10.0%, known coronary artery disease, and estimated glomerular filtration rate ≥60mL/min/1.73m2. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed to body surface area from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to body surface area, ejection fraction, 24-hour ambulatory blood pressure, hematocrit, and NT-proBNP (N-terminal pro b-type natriuretic peptide). Among the 97 participants (90 men [93%], mean [standard deviation] age 62.8 [9.0] years, type 2 diabetes mellitus duration 11.0 [8.2] years, estimated glomerular filtration rate 88.4 [16.9] mL/min/1.73m2, LV mass indexed to body surface area 60.7 [11.9] g/m2), 90 had evaluable imaging at follow-up. Mean LV mass indexed to body surface area regression over 6 months was 2.6 g/m2 and 0.01 g/m2 for those assigned empagliflozin and placebo, respectively (adjusted difference -3.35 g/m2; 95% CI, -5.9 to -0.81g/m2, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference -6.8mmHg, 95% CI -11.2 to -2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference -3.2mmHg; 95% CI, -5.8 to -0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003). Among people with type 2 diabetes mellitus and coronary artery disease, SGLT2 inhibition with empagliflozin was associated with significant reduction in LV mass indexed to body surface area after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02998970.

Eicosapentaenoic Acid (Epa) Inhibits Human Low-Density Lipoprotein Oxidation In A Concentration- And Time-Dependent Manner At Pharmacologic Doses In Vitro

Background and Aims: Eicosapentaenoic acid (EPA) reduces oxidation of low-density lipoproteins (LDL) in patients with hypertriglyceridemia, a benefit that may contribute to lower cardiovascular events. EPA may inhibit LDL oxidation through free radical scavenging at a pharmacologic dose (4 g/d) as measured in plasma in the micromolar range.

Proprotein convertase subtilisin/kexin type 9 in kidney disease.

Chronic kidney disease (CKD) is associated with a substantially increased risk for the development of atherosclerotic cardiovascular (CV) disease. Accordingly, CV mortality is increased even in the earliest stages of CKD. In the general population and in CKD patients, high plasma levels of low-density lipoprotein cholesterol (LDL-C) are crucially involved in the initiation and progression of atherosclerotic vascular lesions. Lowering LDL-C by use of statins and/or ezetimibe represents the gold standard of lipid-lowering therapy, with a great body of evidence from several large clinical trials. Statin therapy reduces CV events in patients with normal and impaired kidney function alike, while the evidence for patients on maintenance haemodialysis is weaker. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease represents a novel lipid-lowering tool. Currently the monoclonal antibodies evolocumab and alirocumab are the approved PCSK9 inhibitors. Despite maximum-tolerated statin therapy, they efficiently further reduce LDL-C plasma levels without any major adverse effects. Moreover, in large clinical outcome trials, both antibodies have been proven to lower CV events. Notably, the LDL-lowering capacity was independent of baseline kidney function and also efficient in patients with moderate CKD. However, patients with severely impaired kidney function, that is, the population at the highest CV risk, have been excluded from those trials. The relevance of the LDL-independent effects of PCSK9 inhibitors, such as lowering lipoprotein(a) or ameliorating dyslipidaemia in patients with nephrotic syndrome, has to be determined. Therefore further specific studies assessing the effects and outcomes of PCSK9-inhibiting treatment in CKD patients are warranted.

Daily Step Counts for Measuring Physical Activity Exposure and Its Relation to Health.

A systematic primary literature review was conducted to evaluate the relationship of physical activity-as measured by daily step counts-with all-cause mortality, cardiovascular disease mortality, incident cardiovascular disease, and type 2 diabetes mellitus; to evaluate the shape of dose-response relationships; and to interpret findings in the context of development of the Physical Activity Guidelines for Americans, Second Edition. A primary literature search encompassing 2011 to March 2018 for existing literature reporting on these relationships was conducted. Eleven pertinent articles were identified. Seven longitudinal studies examined the relationship between daily step counts and mortality, disease incidence, or risk. Two studies examined objectively measured steps per day and all-cause mortality; one was restricted to a relatively small elderly population. One study examined cardiovascular events, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The other four longitudinal studies addressed incident type 2 diabetes. All longitudinal studies reported an inverse relationship between steps per day and outcome risk. In one study, 531 cardiovascular events occurred during more than 45,000 person-years of follow-up. Before intervention, each increment of 2000 steps per day up to 10,000 steps was associated with a 10% lower cardiovascular event rate. Also, for every increase of 2000 steps per day over baseline, there was an 8% yearly reduction in cardiovascular event rate in individuals with impaired glucose tolerance. Daily step count is a readily accessible means by which to monitor and set physical activity goals. Recent evidence supports previously limited evidence of an inverse dose-response relationship of daily steps with important health outcomes, including all-cause mortality, cardiovascular events, and type 2 diabetes. However, more independent studies will be required before these observations can be translated into public health guidelines.

Impact of intensively lowered low-density lipoprotein cholesterol on deferred lesion prognosis.

The aim of this study was to investigate the impact of intensively lowered low-density lipoprotein cholesterol (LDL-C) level on the deferred lesion prognosis after revascularization deferral based on fractional flow reserve (FFR). Lowering LDL-C is associated with lower cardiovascular event rate, but its benefit on the deferred lesion prognosis has not been well evaluated. This retrospective, single-center, observational study analyzed 192 deferred lesions with FFR value >0.80 in 192 patients with stable coronary artery disease. According to the first follow-up LDL-C level, they were assigned to the LOW group (<70 mg/dL) or the HIGH group (≥70 mg/dL). Deferred lesion failure (DLF) was defined as the composite of deferred lesion revascularization and deferred vessel myocardial infarction. Of all participants, 61 and 131 patients were assigned to the LOW and the HIGH group, respectively. During the median follow-up of 2.8 years, DLF occurred in 1 and 14 patients in the LOW group and the HIGH group (1.6% and 10.7%, log-rank p = .043), respectively. The incidence of any unplanned revascularization was also significantly lower in the LOW group than in the HIGH group (3.3% vs. 14.5%, log-rank p = .032). The incidence of DLF was significantly lower in the patients with LDL-C < 70 mg/dL than in those with LDL-C ≥ 70 mg/dL at the first follow-up after FFR-based deferral of revascularization.

Safety and Efficacy of Rivaroxaban When Added to Aspirin Monotherapy Among Stabilized Post‐Acute Coronary Syndrome Patients: A Pooled Analysis Study of ATLAS ACS‐TIMI 46 and ATLAS ACS 2‐TIMI 51

BackgroundA residual risk of ischemic events following an acute coronary syndrome (ACS) remains despite antiplatelet therapy. The addition of an antithrombin as part of a “dual pathway” approach may further improve outcomes as thrombin generation persists for several months post‐ACS. The present study evaluates the safety and efficacy of “dual pathway” therapy (rivaroxaban plus aspirin) as compared with aspirin monotherapy among post‐ACS patients.Methods and ResultsA total of 1477 patients were analyzed in a pooled analysis of subsets of the ATLAS ACS‐TIMI (Anti‐Xa Therapy to Lower cardiovascular events in addition to Aspirin with or without thienopyridine therapy in Subjects with Acute Coronary Syndrome – Thrombolysis in Myocardial Infarction) 46 and ATLAS ACS 2‐TIMI 51 trials including post‐ACS patients receiving aspirin monotherapy and randomized to either rivaroxaban 2.5 mg BID or rivaroxaban 5 mg BID or placebo. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or stroke (ischemic, hemorrhagic, or of uncertain cause). The primary safety end point was TIMI‐non‐coronary artery bypass (CABG) major bleeding. The combined rivaroxaban group (2.5 or 5 mg BID) among stabilized post‐ACS patients on a background of aspirin monotherapy was associated with a significant reduction in the primary end point as compared with placebo (hazard ratio=0.65, 95% CI=0.45–0.92, P=0.016). Although the combined rivaroxaban dose groups were associated with higher rates of non‐CABG TIMI major bleeding, the 2.5 mg dose group was not, and the overall number of patients experiencing a non‐CABG TIMI major bleeding event was low (1.5%).ConclusionsAmong patients in the immediate post‐ACS period, a “dual pathway” approach using aspirin and low‐dose rivaroxaban may reduce the risk of secondary atherothrombotic events, but increase bleeding risk.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00402597; NCT00809965.

Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis

Background: Elevated serum concentrations of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality in patients with chronic kidney disease and those undergoing dialysis. Objectives: We tested the hypotheses that polymorphisms in FGF23, its co-receptor alpha-klotho (KL), and/or FGF23 receptors (FGFR) are associated with cardiovascular events and/or mortality. Methods: We used 1,494 DNA samples collected at baseline from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial, in which patients were randomized to the calcimimetic cinacalcet or placebo for the treatment of secondary hyperparathyroidism. We analyzed European and African Ancestry samples separately and then combined summary statistics to perform a meta-analysis. We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest. Results: rs11063112 in FGF23 was associated with cardiovascular mortality (risk allele = A, hazard ratio [HR] 1.32, meta-p value = 0.004) and HF (HR 1.40, meta-p value = 0.007). No statistically significant associations were observed between FGF23 rs13312789 and SNPs in FGFR4 or KL genes and the outcomes of interest. Conclusions: rs11063112 was associated with HF and cardiovascular mortality in patients receiving dialysis with moderate to severe secondary hyperparathyroidism.

Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance Hemodialysis.

Trimethylamine N-oxide (TMAO), a compound derived from byproducts of intestinal bacteria, has been shown to accelerate atherosclerosis in rodents. To date, there are conflicting data regarding the association of serum TMAO with cardiovascular outcomes in patients with ESKD, a population exhibiting both high serum TMAO and excessive atherosclerosis. We measured baseline serum TMAO concentrations in a subset of participants (n=1243) from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial and conducted post hoc analyses evaluating the association between baseline serum TMAO and cardiovascular outcomes. We observed a wide distribution of serum TMAO in our cohort, with approximately 80% of participants exhibiting TMAO concentrations ≥56 µM and a maximum TMAO concentration of 1103.1 µM. We found no association between TMAO and our primary outcome, a composite of cardiovascular mortality, myocardial infarction, peripheral vascular event, stroke, and hospitalization for unstable angina. Moreover, in unadjusted and adjusted analyses, we observed no relation between TMAO and all-cause mortality, the independent components of our composite outcome, or the original EVOLVE primary outcome. Although we did observe higher TMAO concentrations in white participants, further subgroup analyses did not confirm the previously identified interaction between TMAO and race observed in a prior study in patients receiving dialysis. We found no evidence linking TMAO to adverse clinical outcomes in patients receiving maintenance hemodialysis with moderate to severe secondary hyperparathyroidism.

Factors IX, XI, and XII: potential therapeutic targets for anticoagulant therapy in atherothrombosis.

Atherosclerosis is a leading cause of cardiovascular and neurological ischemic events. Plaque rupture leads to the exposure of highly thrombogenic material with blood and results in the activation of the coagulation cascade, thrombus formation, and embolic events. Although antiplatelets and anticoagulants are used to prevent thromboembolic episodes, bleeding episodes remain the major adverse effect. Decreased ischemic events have been reported while comparing oral rivaroxaban and apixaban with aspirin to improve the therapeutic outcome in several clinical trials, including Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51, Apixaban for Prevention of Acute Ischemic and Safety Events, and GEMINI-ACS-1 phase II clinical trials. However, there were bleeding episodes. Thus, there is an unmet need for better therapeutic strategies. Therefore, the current focus is to target Factors IX, XI, and XII to develop safer and efficient strategies. In this article, we critically reviewed and discussed the limitations of current therapies and the potential of targeting Factors IX, XI, and XII for anticoagulant therapy in atherothrombosis.