Events In High-risk Patients Research Articles

Icosapent ethyl for dyslipidaemia in patients with diabetes and coronary artery disease: Act now to reduce it.

The risk of atherosclerotic cardiovascular disease (ASCVD) can be significantly reduced in patients with diabetes who are undergoing low-density lipoprotein cholesterol-reducing therapies. However, the elevated triglyceride levels seen in diabetic dyslipidaemia can contribute to residual ASCVD risk. Icosapent ethyl (IPE) has recently been shown to substantially reduce major cardiovascular events in high-risk patients with hypertriglyceridaemia who are undergoing statin therapy. In a real-world study of patients with diabetes and acute coronary syndrome (ACS), 17.1% were found to be eligible for treatment with IPE based on Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) criteria. A significant proportion of patients with diabetes and ACS merit receiving IPE therapy, with important implications for evolving clinical practice guidelines and best standard of care.

IMPACT OF FISH OIL SUPPLEMENTATION ON ACUTE VASCULAR INFLAMMATION IN HEALTHY VOLUNTEERS

Acute vascular inflammation (AVI) plays an important role in atherogenesis. Omega-3 fatty acids (O3FA) have anti-inflammatory properties, yet their effects on AVI remain poorly understood. With the recent report that O3FAs reduce cardiovascular (CV) events in high-risk patients with

Effects of PCSK9 inhibitors on LDL cholesterol, cardiovascular morbidity and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors determine a wide reduction of LDL cholesterol, greater than other lipid-lowering agents. The present meta-analysis is aimed at the assessment of PCSK9 inhibitors effect on LDL Cholesterol, cardiovascular morbidity and all-cause mortality. A Medline and Clinicaltrials.gov search for eligible studies until December 1, 2017, was performed. All randomized trials (> 12weeks) comparing PCSK-9 inhibitors with placebo or active drugs were retrieved. Primary endpoints: (a) LDL cholesterol at endpoint; (b) Major cardiovascular events (MACE); (c) All-cause mortality. Data extraction was performed independently by two of the authors, and conflicts resolved by a third investigator. A total of 38 trials fulfilling the inclusion criteria were identified, with mean duration of 36.4weeks. The reduction of LDL cholesterol at endpoint, versus placebo, ezetimibe, and high-dose statins was - 65.3 [- 69.6, - 60.9]%, - 57.7 [- 68.3;- 47.0]%, and - 34.5 [- 40.8;- 28.1]%, respectively, with alirocumab possibly showing a smaller effect than the other drugs of the class. Treatment with PCSK9 inhibitors was associated with a reduction in the incidence of MACE (Mantel-Haenszel Odds Ratio [MH-OR] 0.83 [0.78, 0.88]), with significant effects of alirocumab and evolocumab only. The number needed to treat for 2years for preventing one event was 89. All-cause mortality and cardiovascular mortality were not reduced by treatment with PCSK-9 inhibitors (MH-OR 0.94 [0.84, 1.04] and 0.97[0.86;1.09]). PCSK-9 inhibitors are effective in reducing LDL cholesterol and the incidence of major cardiovascular events in high-risk patients. Bococizumab does not show significant effects on MACE. PROSPERO-CRD42018087640.

Cholesterol-Lowering Agents.

Loss-of-function variants in PCSK9 (proprotein convertase subtilisin-kexin type 9) are associated with lower lifetime risk of atherosclerotic cardiovascular disease) events. Confirmation of these genetic observations in large, prospective clinical trials in participants with atherosclerotic cardiovascular disease has provided guidance on risk stratification and enhanced our knowledge on hitherto unresolved and contentious issues concerning the efficacy and safety of markedly lowering LDL-C (low-density lipoprotein cholesterol). PCSK9 has a broad repertoire of molecular effects. Furthermore, clinical trials with PCSK9 inhibitors demonstrate that reductions in atherosclerotic cardiovascular disease events are more effective in patients with recent myocardial infarction, multiple myocardial infarctions, multivessel coronary artery disease, and lower extremity arterial disease. The potent LDL-C lowering efficacy of PCSK9 inhibitors provides the opportunity for more aggressive LDL-lowering strategies in high-risk patients with atherosclerotic cardiovascular disease and supports the notion that there is no lower limit for LDL-C. Aggressive LDL-C lowering with fully human PCSK9 monoclonal antibodies has been associated by a safety profile superior to that of other classes of LDL-lowering agents. These clinical trials provide evidence that LDL lowering with PCSK9 inhibitors is an effective therapy for lowering cardiovascular events in high-risk patients with LDL-C levels ≥70 mg/dL on maximally tolerated oral therapies, including statins and ezetimibe.

Cardiovascular Effects of Sodium Glucose Cotransporter-2 (SGLT-2) Inhibition in the Setting of Ischemia/Reperfusion Injury

Background and Hypothesis: Recent evidence indicates that sodium glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce the incidence of major adverse cardiovascular events in high risk patients. However, the specific effects of SGLT2i on the cardiovascular system remain poorly defined. This study was designed to test the hypothesis that SGLT2i improves cardiac function and mitigates myocardial infarct size following regional myocardial ischemia and reperfusion injury. 
 Experimental Design: Lean domestic swine received placebo (n=6) or canagliflozin (n=6; 300 mg PO) 24 hours prior to and the morning of an experiment. Hemodynamics, left ventricular pressure and volume were measured in open chest, swine at baseline, during a 60 min coronary occlusion, and during a 2-hour reperfusion period. The degree of myocardial infarction was assessed by staining with 1% tetrazolium. 
 Results: At the onset of ischemia, SGLT2i produced a significant parallel increase in both left ventricular end diastolic (85 ± 9 mL to 129 ± 10 mL; P < 0.05) and end systolic volumes (29 ± 8 mL to 78 ± 9 mL; P < 0.01). This increase in ventricular filling was associated with significant increases in stroke volume (P < 0.05) and stroke work (P < 0.05) relative to untreated controls swine during ischemia. SGLT2i decreased infarct size from 9.4 [Symbol] 2.1% in control swine to 3.1 [Symbol] 0.98% in SGLT2i treated swine. 
 Conclusion: SGLT2 inhibitors significantly improve cardiac contractile function and mitigate myocardial infarct size following regional myocardial ischemia and reperfusion injury in domestic swine.

The Mediterranean Diet: Lost in Translation.

Despite substantive evidence documenting the efficacy of the Mediterranean diet to reduce cardiovascular events, underutilization is common. An overview of the data set supporting the role of the Mediterranean diet as confirmed in both observational and interventional trials should stimulate greater clinician interest in the diet. Additionally, the availability of patient-friendly tools that enable prompt and easy adoption of the Mediterranean diet, that are able to be used by clinicians who claim no special expertise in diet knowledge, should simplify the path to successful dietary change. A large recently published (2018) prospective study of the Mediterranean diet for primary prevention of cardiovascular events confirmed that compared to control, Mediterranean diet is associated with reduced risk for cardiovascular events in high risk patients. Of the tools available to clinicians that might reduce cardiovascular risk, dietary intervention is the one least utilized. The evidence supports the value of dietary intervention with the Mediterranean diet, and methods to effectively employ it within the confines of typical office practice are readily at hand.

Relation of Serum and Urine Renal Biomarkers to Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus and Recent Acute Coronary Syndromes (From the EXAMINE Trial)

A deeper understanding of the interplay between the renal axis and cardiovascular (CV) disease is needed in type 2 diabetes mellitus (T2DM). We aimed to explore the prognostic value of a comprehensive panel of renal biomarkers in patients with T2DM at high CV risk. We evaluated the prognostic performance of both serum (Cystatin C) and urine renal biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 protein, and indices of urinary protein excretion) in 5,380 patients with T2DM and recent acute coronary syndromes in the EXAMINE trial. Patients requiring dialysis within 14 days were excluded. Single- and multimarker covariate-adjusted Cox proportional hazards models were developed to predict times to events. Primary endpoint was composite nonfatal myocardial infarction, nonfatal stroke, or CV death. Median age was 61 years, 68% were men, and mean baseline estimated glomerular filtration rate (eGFR) was 74 mL/min/1.73 m2. During median follow-up of 18 months, 621 (11.5%) experienced the primary endpoint and 326 (6.1%) patients had died. All renal biomarkers were robustly associated with adverse CV events in step-wise fashion, independent of baseline eGFR. However, in the multimarker prediction model, only Cystatin C (per 1 SD) was associated with the primary endpoint (hazard ratio [HR] 1.28 [1.14 to 1.45]; p ≤ 0.001), death (HR 1.51 [1.30 to 1.74]; p ≤ 0.001), and heart failure hospitalization (HR 1.20 [0.96 to 1.49]; p = 0.11). Association between Cystatin C and the primary endpoint was similar in baseline eGFR above and below 60 mL/min/1.73 m2 (Pinteraction > 0.05). In conclusion, serum and urine renal biomarkers, when tested alone, independently predict long-term adverse CV events in high-risk patients with T2DM. In an integrative panel of renal biomarkers, only serum Cystatin C remained independently associated with subsequent CV risk. Renal biomarkers informing various aspects of kidney function may further our understanding of the complex interplay between diabetic kidney disease and CV disease.

GUIDELINES ORIENTED APPROACH TO LIPID LOWERING (GOAL) MEDICAL PRACTICE ACTIVITY (MPA) TO ACHIEVE LOW DENSITY LIPOPROTEIN CHOLESTEROL (LDL-C) TARGETS

Lowering of LDL-C < at least 2.0 mmol/L is recommended to decrease risk for CV events in high risk patients. Despite widespread use of statins, it is estimated that 40 - 50% of Canadian patients with known CVD do not achieve LDL-C target. GOAL is an investigator initiated study aiming to ascertain the use of second and third line therapy and its impact on LDL-C target achievement in a real world setting. GOAL plans to enroll 3000 Canadian high CV risk patients with clinical vascular disease including CAD, cerebrovascular disease, abdominal aortic aneurysm, peripheral arterial disease or familial hypercholesterolemia (FH) and LDL-C > 2.0 mmol/L despite maximally tolerated statin therapy. During follow-up physicians manage patients as clinically indicated but with reminders of CCS Dyslipidemia Guidelines. The program is led by a steering committee supported by the Canadian Heart Research Centre (data collection and physician interactive component) and is IRB approved. As of April 9, 2018, 1585 patients were enrolled (median age 63 years, 42% female) by 237 physicians. Co-morbid conditions included: FH 46%, hypertension 61%, CAD 51%, smoking history 48%, diabetes 37%, other vascular disease 11%, and CKD 9%. Systolic blood pressure was 128 mmHg, diastolic 78 mm Hg, and BMI 29 kg/m2. Baseline LDL-C was 3.4±1.3 , non-HDL-C 4.2±1.5, HDL-C 1.3±0.4, and triglycerides 2.1±1.4 mmol/L. Lipid lowering therapy used at baseline was statin therapy in 75% (with 25% statin intolerant), and 21% ezetimibe. Statins used most frequently were rosuvastatin (39%) and atorvastatin (28%). Physicians indicated their next steps in lowering of LDL-C to be: addition of ezetimibe in 31%, addition of bile acid sequestrant in 5%, and addition of PCSK9 inhibitor in 42%. The three top reasons for not using recommended therapy with ezetimibe were: patient refusal 34%, not needed 25%, and intolerance 17%, while for PCSK9i were: cost 29%, not needed 26% or patient refusal 26%. Additional lipid modifying therapies during follow up are shown in Figure 1. The proportion of patients achieving the CCS recommended LDL-C target of <2.0 mmol/L is shown in Figure 2. Interim assessment of the GOAL program indicates frequent successful add-on of other lipid lowering therapies, associated with a greater proportion of patients achieving CCS Guideline recommended LDL-C target, in high risk patients with an LDL-C above target despite statin therapy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Impact of a dedicated medication access coordinator on PCSK9 inhibitor approval rates

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly reduce the risk of major adverse cardiovascular events in high risk patients. The most significant barrier with these drugs is cost (estimated average wholesale price [AWP] $14K per year). For these drugs to be cost-effective, their cost needs to be ∼1/3 of their current AWP. The use of these drugs requires payer approval with substantial provider and clinic staff resources needed to gain prior authorization (PA).Objectives: To justify the utilization of a disease-state pharmacy medication expert in the cardiology clinic to assist with benefit investigation and prior authorization efforts for this class of medication to optimize prescription approval rates.Methods: A pharmacy technician from the integrated delivery network (IDN) who received training in the role of medication access coordinator (MAC) was placed in the outpatient cardiology clinic late in 2017. The MAC worked with clinic providers, specialty pharmacy, payers, and pharmaceutical company representatives to streamline the traditional methods of benefit investigation and the PA process.Results: From December 2017 to April 2018, the MAC reviewed and assisted with PCSK9 inhibitor PA in 325 cardiac patients. Of the 325 patients, 48 were pending PA, currently denied, or pending medication trial. PA approval in the remaining patients were: 8 with Medicaid ($0 copay); 88 with commercial insurance (≤$10 monthly copay); 80 with Medicare and Amgen Safety Net foundation ($0 copay); 15 pending for the Medicare/pharmaceutical manufacturer foundation; 8 with low income subsidy (LIS) (≤$8.35/90 day copay); 6 with Medicare and alirocumab (Praluent®) Assistance (PASS $0 copay) with 4 others pending approval; and 1 with the Pan Foundation. The remaining 67 had Medicare coverage and an adjusted gross income >$83,000/year. These patients opted not to receive treatment due to cost. As an indicator of the success of the MAC initiative, the success rate of evolocumab (Repatha®) approvals for the IDN across the country is 82%. This is compared to 62% regionally and 60% nationally for non-IDN patients. This shows the impact of the implementation and approval success of the MAC role.Conclusions: There is clear benefit of the MAC in the cardiology clinics of the IDN. PA rates with these drugs are among the most challenging of all specialty drugs. By channeling benefit investigation and PA through the MAC, PA approval was increased by 20%. Similar approaches using a MAC in other disease states should improve specialty pharmacy medication approvals.

ESC/EAS clinical guidance recommendations: impact on patient eligibility for PCSK9 inhibitor therapy

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been demonstrated to significantly reduce the risk of recurrent adverse vascular events in high-risk patients with a history of coronary, cerebral, or peripheral artery disease. The primary barrier to the use of these drugs is their cost. Use of these drugs in the highest-risk patients would improve their cost-effectiveness. A clinical guidance for the use of these drugs based on vascular risk was recently published.Objectives: To determine how clinical guidance recommendations would impact the numbers of patients eligible to receive PCSK9 inhibitor therapy.Methods: 2000 consecutive patients admitted to an academic medical center referred to a cardiology consult service with documented atherosclerotic cardiovascular disease (ASCVD) were evaluated for PCSK9 inhibitor eligibility using the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) clinical guidance recommendations. Any patient with ASCVD with an LDL-C >140 mg/dl was considered eligible for PCSK9 inhibitor therapy. Patients with an LDL-C >100 mg/dl had to meet additional criteria to be eligible. These criteria included (1) diabetes with target organ damage or another risk factor; (2) severe or extensive CAD; or (3) progressive/accelerated ASCVD, ischemic stroke, or revascularization in the coronary, cerebral, or peripheral arterial system within 2 years of a previous ASCVD event.Results: Mean age was 64.9 ± 12.7 years; 66% were men and 34% were women; 80% were white, 9% were black, 10% were Latino and 1% other. Eligibility for PCSK9 inhibitor therapy included 163 patients with LDL-C >140 mg/dl and 892 patients with LDL-C >100 mg/dl with additional risk factors. Additional risk factors were diabetes plus comorbidity in 318 patients; severe or extensive CAD in 317 patients; and progressive/accelerated ASCVD in 257 patients. The total number of patients eligible for PCSK9 inhibitor therapy using the ESC/EAS criteria was 1055 (53%).Conclusions: Previous studies have estimated 15 to 25% of patients with a history of vascular disease to be eligible for PCSK9 inhibitors. In this high-risk cardiac population, over 50% of patients would be PCSK9 inhibitor eligible. The cost to treat this proportion of patients would represent an overwhelming burden to any health system using current drug costs. Medication access coordinators need to play a critical role in the selection and evaluation of patients eligible for PCSK9 inhibitor therapy to maximize cost-efficiency of this therapy.

Perioperative urinary thromboxane metabolites and outcome of coronary artery bypass grafting: a nested case-control study

ObjectiveAs a marker of in vivo thromboxane generation, high-level urinary thromboxane metabolites (TXA-M) increase the occurrence of cardiovascular events in high-risk patients. To investigate whether perioperative urinary TXA-M level is...

Appropriateness of Pharmacologic Prophylaxis against Deep Vein Thrombosis in Medical Wards of an Ethiopian Referral Hospital.

Background Most of hospitalized patents are at risk of developing deep vein thrombosis (DVT). The use of pharmacological prophylaxis significantly reduces the incidence of thromboembolic events in high risk patients. The aim of this study was to assess appropriateness of DVT prophylaxis in hospitalized medical patients in an Ethiopian referral hospital. Methods Cross-sectional study design was employed. Patients with a diagnosis of DVT, taking anticoagulant therapy, and those who refused to participate were excluded from the study. Two hundred and six patients were included in the study using simple random sampling method. Modified Padua Risk Assessment Model was used to determine the risk of thromboembolism. SPSS (version 21) was used for analysis. Result The total risk score for the study subjects ranged from 0 to 11 with a mean score of 3.41 ± 2.55. Nearly half (47.6%) of study participants had high risk to develop thromboembolism. Thrombocytopenia (platelets < 50 billion/L) or coagulopathy, active hemorrhage, and end stage liver disease (INR > 1.5) were the frequently observed absolute contraindications that potentially prevent patients from receiving thromboprophylaxis. Thromboprophylaxis use in nearly one-third (31.6%) of patients admitted in the medical ward of UoGRH was irrational. Patients who had high risk for thromboembolism are more likely to be inappropriately managed for their risk of thromboembolism and patients with thrombocytopenia or coagulopathy were more likely to be managed appropriately. Conclusion There is underutilization of pharmacologic thromboprophylaxis in medical ward patients. Physicians working there should be aware of risk factors for DVT and indications for pharmacologic thromboprophylaxis and should adhere to guideline recommendations.

Individualized antithrombotic therapy in high-risk cardiovascular patients.

Recent guidelines suggest dual antiplatelet therapy (DAPT) after 'drug-eluting' stent (DES) implantation for 6months in stable patients and for 12months in patients after acute coronary syndrome. Serious complications after stent implantation include stent thrombosis, recurrent myocardial infarction, ischemic stroke, cardiovascular death and bleeding. These complications also occur beyond 1 year after coronary intervention. Thus, it is important to consider whether a prolonged DAPT (>12months after percutaneous coronary intervention) is of benefit to lower thrombo-ischemic events in high-risk patients. This review addresses the results of recent randomized clinical studies (DAPT, ITALIC, OPTIDUAL and PEGASUS) and meta-analyses to support the author's view of which patient collectives might benefit from prolonged DAPT.

Inhibition of Sodium Glucose Cotransporter‐2 Preserves Cardiac Function during Regional Myocardial Ischemia via a Frank‐Starling Mechanism

Recent evidence indicates that sodium glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce the incidence of major adverse cardiovascular events in high risk patients. However, the specific effects of SGLT2i on the cardiovascular system remain poorly defined. This study tested the hypothesis that SGLT2i improves cardiac function during acute regional myocardial ischemia and reperfusion. Lean domestic swine (~50 kg; control (n = 6), SGLT2i (n = 5)) were randomized to receive either placebo or oral doses of canagliflozin (300 mg) 24 hours prior to and the morning of a terminal experimental procedure. Measurements were obtained in open chest, anesthetized swine at baseline, during a 30 min complete occlusion of the circumflex coronary artery, and during a 2 hour reperfusion period. Blood pressure (85 ± 6 mmHg), heart rate (78 ± 7 beats/min), coronary flow (0.40 ± 0.05 mL/min/g), and myocardial oxygen consumption (43 ± 6 μL O2/min/g) were unaffected by canagliflozin treatment at rest and were not significantly altered by ischemia/reperfusion in either group. At the onset of ischemia, SGLT2i produced a significant parallel increase in both left ventricular end diastolic (85 ± 9 mL to 129 ± 10 mL; P < 0.05) and end systolic volumes (29 ± 8 mL to 78 ± 9 mL; P < 0.01) that was manifest ~30 to 90 sec post coronary artery occlusion. Left ventricular volumes remained elevated throughout the ischemic period and returned to baseline levels following ~30 min of reperfusion. Ventricular volumes remained unchanged in control swine throughout the entire protocol. Canagliflozin-mediated increases in end diastolic volume were directly associated with significant increases in stroke volume (P < 0.05) and stroke work (P < 0.05) relative to untreated controls swine during ischemia. SGLT2i also increased cardiac efficiency (P < 0.05), as defined by stroke work/myocardial oxygen consumption. No differences in myocardial substrate uptake of glucose (P = 0.54) or lactate (P = 0.16) were noted between groups at any experimental time point. These data support the hypothesis that SGLT2i preserves cardiac contractile function during regional myocardial ischemia via activation of a Frank-Starling mechanism and independent of alterations in myocardial substrate selection. Attached figure illustrates control responses (black) and SGLT2i responses (red). Support or Funding Information NIH HL117620 Representative pressure volume loops from control (black) and SGLT2i treated (red) animals under baseline (solid) and ischemic (dashed) conditions are presented in panels A & B. Panels C & D illustrate the rate of change to ventricular volume parameters present in treated (D) but not control (C) animals subsequent to onset of ischemia. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

THE A-BODY-SHAPE-INDEX AND TYPE 2 DIABETES ARE MUTUALLY INDEPENDENT PREDICTORS OF CARDIOVASCULAR EVENTS RISK IN ANGIOGRAPHIED CORONARY PATIENTS

The A-Body-Shape-Index (ABSI) is calculated based on waist circumference, height and BMI and provides a measure of visceral adiposity. In the general population, this index has been associated with premature mortality. Its power to predict cardiovascular events in high-risk patients is not known and

Patient at intermediate cardiovascular risk: statins, yes! - antihypertensive therapy, maybe.

Patient at intermediate cardiovascular risk: statins, yes! - antihypertensive therapy, maybe.

Effect of Mechanically Expanded vs Self-Expanding Transcatheter Aortic Valve Replacement on Mortality and Major Adverse Clinical Events in High-Risk Patients With Aortic Stenosis

Transcatheter aortic valve replacement (TAVR) is established for selected patients with severe aortic stenosis. However, limitations such as suboptimal deployment, conduction disturbances, and paravalvular leak occur. To evaluate if a mechanically expanded valve (MEV) is noninferior to an approved self-expanding valve (SEV) in high-risk patients with aortic stenosis undergoing TAVR. The REPRISE III trial was conducted in 912 patients with high or extreme risk and severe, symptomatic aortic stenosis at 55 centers in North America, Europe, and Australia between September 22, 2014, and December 24, 2015, with final follow-up on March 8, 2017. Participants were randomized in a 2:1 ratio to receive either an MEV (n = 607) or an SEV (n = 305). The primary safety end point was the 30-day composite of all-cause mortality, stroke, life-threatening or major bleeding, stage 2/3 acute kidney injury, and major vascular complications tested for noninferiority (margin, 10.5%). The primary effectiveness end point was the 1-year composite of all-cause mortality, disabling stroke, and moderate or greater paravalvular leak tested for noninferiority (margin, 9.5%). If noninferiority criteria were met, the secondary end point of 1-year moderate or greater paravalvular leak was tested for superiority in the full analysis data set. Among 912 randomized patients (mean age, 82.8 [SD, 7.3] years; 463 [51%] women; predicted risk of mortality, 6.8%), 874 (96%) were evaluable at 1 year. The primary safety composite end point at 30 days occurred in 20.3% of MEV patients and 17.2% of SEV patients (difference, 3.1%; Farrington-Manning 97.5% CI, -∞ to 8.3%; P = .003 for noninferiority). At 1 year, the primary effectiveness composite end point occurred in 15.4% with the MEV and 25.5% with the SEV (difference, -10.1%; Farrington-Manning 97.5% CI, -∞ to -4.4%; P<.001 for noninferiority). The 1-year rates of moderate or severe paravalvular leak were 0.9% for the MEV and 6.8% for the SEV (difference, -6.1%; 95% CI, -9.6% to -2.6%; P < .001). The superiority analysis for primary effectiveness was statistically significant (difference, -10.2%; 95% CI, -16.3% to -4.0%; P < .001). The MEV had higher rates of new pacemaker implants (35.5% vs 19.6%; P < .001) and valve thrombosis (1.5% vs 0%) but lower rates of repeat procedures (0.2% vs 2.0%), valve-in-valve deployments (0% vs 3.7%), and valve malpositioning (0% vs 2.7%). Among high-risk patients with aortic stenosis, use of the MEV compared with the SEV did not result in inferior outcomes for the primary safety end point or the primary effectiveness end point. These findings suggest that the MEV may be a useful addition for TAVR in high-risk patients. ClinicalTrials.gov Identifier: NCT02202434.

Long-Term Statin Adherence in Rural Versus Urban Patients at High Atherosclerotic Cardiovascular Disease Risk

Introduction: Australian rural populations experience a greater burden of cardiovascular disease (CVD) compared to their urban counterparts. Statins are critical in the prevention of cardiovascular events in high-risk patients; however, the difference between long-term adherence in rural and urban populations is unknown.

Residual renal and cardiovascular disease risk in conventionally-treated patients with type 2 diabetes: the potential of non-traditional biomarkers.

Diabetes is a leading cause of chronic kidney disease (CKD) in the developed world. Promoters of the progression of kidney disease include the traditional profile of cardiovascular risk factors. However, the development of CKD and vulnerability to end-stage renal disease (ESRD) is highly variable. Determinants of the susceptibility to ESRD may include non-traditional risk factors such as gene-environment interactions, socio-geographic factors and/or treatment strategies. We review the conflicting clinical relevance of studies implicating pathways related to oxidative stress. These pathways are strongly implicated in the phenotype of some groups of high-risk patients and could assume importance in clinical care. Recent clinical trial evidence has shown that newer glucose-lowering agents also have beneficial effects on reducing the incidence of renal dysfunction and cardiovascular events in high-risk patients. Research is required to identify which patients will benefit most from newer approaches to managing diabetes. Understanding the relationship of non-traditional risk factors to renal and cardiovascular disease could help clinicians targeting new therapeutic approaches in the management of type 2 diabetes.

Ticagrelor: A Review in Long Term Secondary Prevention of Cardiovascular Events.

Ticagrelor (Brilique®) is an orally administered P2Y12 inhibitor. A long-term (maintenance) regimen of ticagrelor 60mg twice daily is indicated in the EU for coadministration with low-dose aspirin 75-150mg/day for the secondary prevention of atherothrombotic events in high-risk patients with a history of myocardial infarction (MI) of at least 1year. Approval is based on the results of the PEGASUS-TIMI 54 trial that compared ticagrelor with placebo (in conjunction with low-dose aspirin) in stable patients who had had a spontaneous MI 1-3years prior to enrolment and were at high risk of atherothrombotic events. At 3years, the composite primary efficacy endpoint of cardiovascular (CV) death, MI or stroke occurred in significantly fewer ticagrelor 60mg twice daily than placebo recipients. Long-term ticagrelor had a manageable tolerability and safety profile. The risk of TIMI major bleeding (primary safety endpoint) was significantly increased in ticagrelor 60mg twice daily versus placebo recipients; however, the risk appeared to decline after the first year of therapy. Landmark analyses have demonstrated that patients with a history of MI remain at a persistent high risk of the composite primary endpoint up to 5years after the event. Furthermore, these analyses demonstrated that the efficacy of ticagrelor 60mg twice daily was maintained over time, with less excess in bleeding after the first year. Thus, long-term dual antiplatelet therapy with ticagrelor 60mg twice daily and low-dose aspirin is a valuable new option for the secondary prevention of atherothrombotic events in stable, high-risk patients with a history of MI of at least 1year.