Stable Cardiovascular Disease Research Articles

Estimating individual lifetime benefit and bleeding risk of adding rivaroxaban to aspirin for patients with stable cardiovascular disease: results from the COMPASS trial.

Adding rivaroxaban to aspirin in patients with stable atherosclerotic disease reduces the recurrence of cardiovascular disease (CVD) but increases the risk of major bleeding. The aim of this study was to estimate the individual lifetime treatment benefit and harm of adding low-dose rivaroxaban to aspirin in patients with stable cardiovascular disease. Patients with established CVD from the COMPASS trial (n = 27390) and SMART prospective cohort study (n = 8139) were used. Using the pre-existing lifetime SMART-REACH model for recurrent CVD, and a newly developed Fine and Gray competing risk-adjusted lifetime model for major bleeding, individual treatment effects from adding low-dose rivaroxaban to aspirin in patients with stable CVD were estimated, expressed in terms of (i) life-years free of stroke or myocardial infarction (MI) gained; and (ii) life-years free from major bleeding lost. Calibration of the SMART-REACH model for prediction of recurrent CVD events in the COMPASS study was good. The major bleeding risk model as derived in the COMPASS trial showed good external calibration in the SMART cohort. Predicted individual gain in life expectancy free of stroke or MI from added low-dose rivaroxaban had a median of 16 months (range 1-48 months), while predicted individualized lifetime lost in terms of major bleeding had a median of 2 months (range 0-20 months). There is a wide distribution in lifetime gain and harm from adding low-dose rivaroxaban to aspirin in individual patients with stable CVD. Using these lifetime models, benefits and bleeding risk can be weighed for each individual patient, which could facilitate treatment decisions in clinical practice.

Unsaturated fatty acid composition in serum phospholipids in patients in the acute phase of myocardial infarction.

Recent improvements in optimal cardiovascular therapy have questioned the beneficial effects of polyunsaturated fatty acids (PUFAs) observed in previous studies. We investigated the fatty acid (FA) composition in serum phospholipids in patients with an established acute phase of myocardial infarction (MI) and in high‑risk patients with stable atherosclerotic cardiovascular disease (CVD). We studied 83 patients hospitalized within 12 hours from the onset of the first clinical symptoms of MI. As a control group, we assessed 74 patients at high cardiovascular risk with an established stable atherosclerotic CVD treated at an outpatient cardiology clinic. Gas chromatography was used to evaluate the FA composition in serum phospholipids in both groups. The final analysis included 52 patients with acute MI and 74 controls. In both groups, saturated FAs constituted the largest fraction of serum phospholipid FAs (median, 1574.67 μmol/l), followed by n‑6 PUFAs (median, 1106.99 μmol/l). The levels of total saturated FAs, monounsaturated FAs, n‑6 PUFAs, as well as the ratio of n‑6 to n‑3 PUFAs significantly differed between groups. Palmitic acid constituted the largest fraction of serum phospholipids both in patients and controls (31.9% and 31.16%, respectively). In a multivariate logistic regression analysis, body mass index, low‑density lipoprotein cholesterol, aspartate aminotransferase, high‑sensitivity C‑reactive protein, and palmitoleic and eicosadienoic acids were independently associated with MI. We showed major differences in the FA composition of serum phospholipids between patients with acute MI and high‑risk individuals with stable atherosclerotic CVD. Eicosadienoic and palmitoleic acids, apart from typical cardiovascular risk factors, were independently associated with MI.

Covering the Cover

Covering the Cover

Acute Effects of Whole-Body Vibration Training on Endothelial Function and Cardiovascular Response in Elderly Patients with Cardiovascular Disease.

The aim of this single-arm pilot study was to determine the effects of whole-body vibration training (WBVT) on endothelial function in elderly patients with cardiovascular diseases, as well as its safety. A total of 20 elderly patients with stable cardiovascular diseases underwent WBVT, which consisted of five static resistance training exercises (squats, wide stance squats, toe-stands, squats + band, and front lunges). The parameters of WBVT included vertical vibrations, 30 Hz frequency, and a 3-mm peak-to-peak amplitude. Each vibration session lasted 30 seconds, with 120 seconds of rest between sessions. Before and after WBVT, the reactive hyperemia peripheral arterial tonometry index (RH-PAT index) and transcutaneous oxygen pressure (tcPO2) were recorded as a measure of endothelial function and peripheral blood circulation. Systolic blood pressure, diastolic blood pressure, heart rate, and arterial oxygen saturation of pulse oximetry (SpO2) were measured at each rest interval as well as before and after WBVT. All patients completed our WBVT protocol without adverse events. The RH-PAT index significantly increased following WBVT (1.42 to 2.06, P < 0.001). There were no significant changes in heart rate (P = 0.777), systolic blood pressure (P = 0.183), diastolic blood pressure (P = 0.925), or SpO2 (P = 0.248) during WBVT. In conclusion, we demonstrated the acute effects of WBVT on endothelial function, with no reports of adverse events. These findings support the need for further randomized controlled studies to investigate the long-term effects of WBVT.

Effect of long-term remote ischemic conditioning on inflammation and cardiac remodeling

Background. Remote ischemic conditioning (RIC) protects against acute ischemia-reperfusion injury and may have beneficial effects in patients with stable cardiovascular disease. We investigated the effect of long-term RIC treatment in patients with chronic ischemic heart failure (CIHF). Methods. Prespecified post-hoc analysis of a prospective, exploratory and outcome-assessor blinded study. Twenty-one patients with compensated CIHF and 21 matched controls without heart failure or ischemic heart disease were treated with RIC once daily for 28 ± 4 days. RIC was conducted as 4 cycles of 5 minutes upper arm ischemia followed by 5 minutes of reperfusion. We evaluated circulating markers of inflammation and cardiac remodeling at baseline and following long-term RIC. Results. RIC reduced C-reactive protein from 1.5 (0.6–2.5) to 1.3 (0.6–2.1) mg/l following long-term RIC treatment (p = .02) and calprotectin from 477 (95% CI 380 to 600) to 434 (95% CI 354 to 533) ng/ml (p = .03) in patients with CIHF, but not in matched controls. Overall, RIC did not affect circulating markers related to adaptive or innate immunology or cardiac remodeling in patients with CIHF. Among patients with CIHF and N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels above the geometric mean of 372 ng/l, long-term RIC treatment reduced soluble ST2 (n = 9) from 22.0 ± 3.7 to 20.3 ± 3.9 ng/ml following long-term RIC treatment (p = .01). Conclusion. Our findings suggest that long-term RIC treatment has mild anti-inflammatory effects in patients with compensated CIHF and anti-remodeling effects in those with increased NT-proBNP levels. This should be further investigated in a randomized sham-controlled trial.

Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin

Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. We performed a 3× 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n= 8791) or placebo (n= 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. In a large placebo-controlled randomized trial, we found thatpantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.

Effects of Extended-Release Niacin on Quartile Lp-PLA2 Levels and Clinical Outcomes in Statin-treated Patients with Established Cardiovascular Disease and Low Baseline Levels of HDL-Cholesterol: Post Hoc Analysis of the AIM HIGH Trial.

Lipoprotein-associated phospholipase A2 (LpPLA2) is an inflammatory marker that has been associated with the presence of vulnerable plaque and increased risk of cardiovascular (CV) events. To assess the effect of extended-release niacin (ERN) on Lp-PLA2 activity and clinical outcomes. We performed a post hoc analysis in 3196 AIM-HIGH patients with established CV disease and low baseline levels of high-density lipoprotein cholesterol (HDL-C) who were randomized to ERN versus placebo on a background of simvastatin therapy (with or without ezetimibe) to assess the association between baseline Lp-PLA2 activity and the rate of the composite primary end point (CV death, myocardial infarction, stroke, hospitalization for unstable angina, and symptom-driven revascularization). Participants randomized to ERN, but not those randomized to placebo, experienced a significant 8.9% decrease in LpPLA2. In univariate analysis, the highest quartile of LpPLA2 activity (>208 nmol/min/mL, Q4) was associated with higher event rates compared to the lower quartiles in the placebo group (log rank P = .032), but not in the ERN treated participants (log rank P = .718). However, in multivariate analysis, adjusting for sex, diabetes, baseline LDL-C, HDL-C, and triglycerides, there was no significant difference in outcomes between the highest Lp-PLA2 activity quartile versus the lower quartiles in both the placebo and the ERN groups. Among participants with stable CV disease on optimal medical therapy, elevated Lp-PLA2 was associated with higher CV events; however, addition of ERN mitigates this effect. This association in the placebo group was attenuated after multivariable adjustment, which suggests that Lp-PLA2 does not improve risk assessment beyond traditional risk factors.

Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial.

Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. We performed a 3× 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P= .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n= 982; 95% confidence interval, 609-2528). In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.

PDG35 COST-EFFECTIVENESS ANALYSIS OF LOW-DOSE RIVAROXABAN PLUS ASPIRIN FOR THE PATIENTS WITH STABLE CARDIOVASCULAR DISEASE IN TAIWAN SETTING

COMPASS study showed that low-dose rivaroxaban plus aspirin were more efficacious than aspirin alone in the treatment of stable cardiovascular diseases (CVDs), but the cost-effectiveness has been a concern. Hence, this study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin for the patients with stable CVDs from the Taiwanese national payer’s perspective. We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life years (QALYs) of low-dose rivaroxaban plus aspirin and aspirin alone. Transitional probabilities were derived from COMPASS study, while costs and utilities were obtained from Taiwan National Health Insurance database and published studies. One-way, scenario and probabilistic sensitivity analyses (PSA) were performed to evaluate the uncertainty, and the incremental cost-effectiveness ratio (ICER) value was presented as our outcome. Threshold of willingness-to-pay (WTP) was set at USD $20,000 and $60,000. All analyses were operated by Treeage 2019. Although low-dose rivaroxaban plus aspirin had more costs ($238,944), they simultaneously produced more QALYs (16.47). Likewise, aspirin alone had fewer costs ($218,104) and QALYs (15.93). The ICER of low-dose rivaroxaban plus aspirin versus aspirin alone was $ 38.591 per QALYs gained. PSA showed that the probability of cost-effectiveness for low-dose rivaroxaban plus aspirin and aspirin alone was 1.2% and 98.8% at $20,000, but 76.9% and 23.1% at $ 60,000. This study revealed that low-dose rivaroxaban plus aspirin is likely to be a cost-effective alternative to aspirin with more QALY gained in the patients with stable CVDs from the national payer’s perspective in Taiwan. The pharmacoeconomic attraction of low-dose rivaroxaban plus aspirin might be influenced by the threshold of WTP. The result could provide a scientific reference for the policymakers in the making of treatment guideline or medical payment in Taiwan.

122 Diagnosis and Management of Testosterone Deficiency – Comparison of Current Guidelines

Testosterone deficiency (TD) is characterized by low levels of testosterone (T) with associated signs and symptoms. Several controversies related to the diagnosis and management of TD have been identified. In an attempt to provide clarity for patients and healthcare providers, several professional organizations have developed clinical practice guidelines focused specifically on TD. We compare current guidelines for the diagnosis and management of TD, as well as special considerations for specific patient populations. Guidelines from the following organizations were included for analysis: American Urological Association (AUA – 2018), Canadian Medical Association (CMAJ – 2015), European Association of Urology (EAU – 2018), and Endocrine Society (ES – 2018). The comparison focused on the biochemical definition (cut-off) for low T, principles of management of TD, and recommendations for patients with low-to-normal total testosterone, prostate cancer, or cardiovascular disease. General diagnostic and management principles are in agreement, however specific biochemical cut-offs range between 8 to 10.4 nmol/L (Table 1). The CMAJ guideline has no specific cut-off for low T and requires only one lab measurement of total T as opposed to the two measurements required in other guidelines. In patients with low-to-normal total T, there is consensus among the guidelines in recommending further hormonal evaluation. However, only the CMAJ guideline provides additional recommendations for testosterone replacement therapy (TRT) by suggesting a 3-month therapeutic trial if patients are symptomatic. The ES guideline has the strictest recommendations for patients with TD and prostate cancer. Other guidelines generally recommend against TRT in patients with metastatic prostate cancer. Although there is limited evidence linking TRT and risk of cardiovascular events (MI, stroke, sudden CV death), the AUA and EAU guidelines impose more restrictions in offering TRT to patients with cardiovascular disease. Notably, the AUA guideline recommends against TRT if patients experienced a cardiovascular event within the past 3-6 months, while the EAU guideline states that TRT is contraindicated in patients with NYHA Class IV heart failure. In contrast, the CMAJ guideline recommends TRT in patients with stable cardiovascular disease.

COMPARATIVE EVALUATION OF EFFICACY AND SAFETY OF ASPIRIN + CLOPIDOGREL WITH ASPIRIN+TICAGRELOR IN PATIENTS WITH CARDIOVASCULAR DISEASES. AN OBSERVATIONAL STUDY.

Background: Coronary artery disease (CAD) is one of the most common causes of mortality and morbidity in both developed and developing countries. It is a leading cause of death in India, and its contribution to mortality is rising. Platelets play an essential role in the pathogenesis of acute coronary syndromes (ACS). Therefore an important part of the treatment of ACS, and of primary and secondary preventive measures in coronary heart disease, consists of antiplatelet treatment. Dual antiplatelet therapy (DAPT) provides more intense platelet inhibition than single antiplatelet therapy resulting in incremental reductions in the risk of thrombotic events after percutaneous coronary intervention (PCI) or ACS, but it has been associated with an increased risk of major bleeding. It is interesting to consider that there is no Indian data on the efficacy of recently developed antiplatelet drugs other than in combination with aspirin, and that we remain unaware of the extent to which combinations with aspirin improve efficacy but increase risk.&#x0D; Methodology: Study was prospective, observational clinical study carried out in the Department of Medicine, of Index Medical College Hospital &amp; Research Centre. A total of 80 patients with CAD were enrolled for the study and were equally divided in two groups each of 40 for evaluating efficacy and safety of dual antiplatelet therapy. Follow-up was done at 8 weeks, 16 weeks, and 24 weeks, patients were asked to provide information regarding their current medications, any morbidity and their complications [if any]. Demographic parameters were analyzed by descriptive statistics. Comparison between groups was done by Chi–square Test. Survival analysis was done by suitable statistical method.&#x0D; Result: The median age was 55 years in group 1 and 57 years in group 2. Hypertension was most common associated disorders in group 1 [25 (62.55%)] and group 2 [27 (67.5%)], which was followed by diabetes and dyslipidemia. index events for present study enrolment was unstable angina, non–ST-segment elevation MI, ST-segment elevation MI and others amongs the study groups. With 6 months of follow-up, the rate of the primary event like death from any cause was 7.5 percent in the clopidogrel plus aspirin group and 2.5 percent in the ticagrelor plus aspirin group. The primary safety end point (severe bleeding) was 2.5 % in the clopidogrel plus group 1 and none in group 2.&#x0D; Conclusion: the combination of clopidogrel plus aspirin was found to be non inferior to aspirin plus ticagrelor dual therapy in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes among patients with stable cardiovascular disease or multiple cardiovascular risk factors. The risk of moderate to severe bleeding was increased slightly in both the groups. Our findings do support the use of dual antiplatelet therapy across the broad population tested where single antiplatelet therapy are not giving maximum benefits&#x0D; Keywords: Acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), Coronary artery disease (CAD), Dual antiplatelet therapy (DAPT)

Interpreting the Findings From the Recent PCSK9 Monoclonal Antibody Cardiovascular Outcomes Trials.

The recent development of monoclonal antibodies targeted to proprotein convertase subtilisin/kexin type 9 (PCSK9), e.g., PCSK9 inhibitors has revolutionized the landscape of lipid management. Many clinical trials assessing this class have demonstrated remarkable and consistent reductions in low-density lipoprotein-cholesterol. Moreover, the GLAGOV trial demonstrated the efficacy of evolocumab, when added to statin therapy, in reducing the progression of atherosclerosis measured by serial intravascular ultrasound, with the first suggestion of continued benefit down to LDL-C levels of 0.5 mmol/L (20 mg/dL). This trial was followed by the FOURIER Cardiovascular Outcomes trial in more than 27,000 patients with stable atherosclerotic cardiovascular disease (ASCVD) where evolocumab reduced the primary endpoint of atherosclerotic events by 15%, without significant safety differences between treatment groups. Furthermore, subgroup analyses suggested greater benefits seen in those with longer exposure to evolocumab recent acute coronary syndrome, multiple myocardial infarctions, multivessel coronary artery disease, peripheral arterial disease, as well as the subgroup who achieved very low low-density lipoprotein-cholesterol levels of below 0.3 mmol/L (10 mg/dL). Moreover, the EBBINGHAUS substudy demonstrated no differences in objectively measured cognitive function between treatment groups. The SPIRE 2 trial evaluating bococizumab in high-risk patients with baseline LDL-C ≥2.6 mmol/L (100 mg/dL) demonstrated significant atherosclerotic risk reduction, but the trial and further development of the drug was prematurely discontinued due to substantial attenuation of the LDL-C effect over time due to the development of neutralizing antibodies. Finally, the ODYSSEY Cardiovascular Outcomes trial testing alirocumab in subjects with recent (<1 year) acute coronary syndrome demonstrated a 15% relative risk reduction in the primary composite outcome, as well as a significant reduction in total mortality. Greater benefits were noted in those whose LDL-C at baseline was 2.6 mmol/L (100 mg/dL) or greater. These trials collectively demonstrate the added efficacy of PCSK9 inhibitors over moderate and high-intensity statin therapy for unprecedented low-density lipoprotein-cholesterol reduction and incremental ASCVD risk reduction.

Factors Associated with Bleeding Events in Patients Receiving Rivaroxaban for Venous Thromboembolism: A Real World Experience

Introduction:Rivaroxaban is a target specific oral anticoagulant approved for treatment of deep venous thromboembolism (DVT), pulmonary embolism (PE) and risk reduction in patients with DVT/PE requiring continued anticoagulation. The XALIA study showed a reduced bleeding risk compared to standard anticoagulation therapy; however, there is paucity of data regarding correlates of bleeding risk amongst patients receiving rivaroxaban in the community setting. We aimed to investigate the clinical factors associated with bleeding events (BE) in patients receiving rivaroxaban for treatment of DVT/PE.Methods:A retrospective study was conducted at John H. Stroger, Jr. Hospital of Cook County. We screened the charts of 837 patients who received rivaroxaban from January 1, 2015 to April 01, 2018. Patients with DVT/PE were included in the study (n=271). Patients with atrial fibrillation and those receiving rivaroxaban for prophylaxis were excluded. Any reported BE was recorded as either major or minor bleeding event. Major BE was defined as events requiring hospitalization, blood transfusions or significant drop in hemoglobin (>2gm/dL). Rest of the BE were classified as minor BE. Socio-demographic and clinical factors were collected. Chi-square test and fisher exact test were used as the tests of trend. Multivariate logistic regression models were used to quantify the independent predictors. Odds ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained.Results:The study included 271 patients, of which 68.3% were African-American, 14.4% were Caucasian, and 12.9% were Hispanic. Median age was 53 years and 60.9% patients were men. Bleeding events were reported in 11.4% (n=31) patients with 6.3% major bleeding events and 5.2% minor bleeding events. Only concurrent use of aspirin (23.8% vs. 9.2%; OR 3.10, 95% CI 1.34-7.17, P = 0.008) was significantly associated with bleeding events. None of the clinical parameters, like abnormal liver function tests (11.4%), cirrhosis (3.3%), chronic kidney disease stage 3 or worse (7.6%), prior use of warfarin (29.9%) or low molecular weight heparin (18.1%) were associated with bleeding events. In multivariate model adjusted for age, gender and race, concurrent use of aspirin (aOR 3.06, 95% CI 1.23-7.62, P = 0.017) remained independent predictor of bleeding events.Conclusion:In the community practice, aspirin (81mg or 325mg) is prescribed for cardio-protection. A recently concluded trial showed a better cardioprotective effect of combining rivaroxaban and aspirin, without increase in BE in patients with stable cardiovascular disease. However, such data is not evident in patients receiving rivaroxaban for DVT/PE. Our study shows an increased rate of bleeding events in such patients with concurrent use of aspirin. Our study population comprises of two-third African-American patients who are under-represented in the clinical trials. Based on our results we would suggest further investigation in safety of prescribing aspirin with rivaroxaban in patients with DVT/PE in prospective trials. DisclosuresNo relevant conflicts of interest to declare.

Plasma levels of apolipoproteins C-III, A-IV, and E are independently associated with stable atherosclerotic cardiovascular disease

Background and aimsDyslipidemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). As key regulators of lipoprotein metabolism, apolipoproteins (apos) are discussed as vascular risk factors. This study aimed to analyze associations of major plasma apos with coronary artery disease (CAD), peripheral artery disease (PAD) and carotid artery plaque (CAP) to elucidate their diagnostic potential in risk assessment. MethodsApoA-I, apoA-II, apoA-IV, apoB-100, apoC-I, apoC-III, apoE, and apoJ were simultaneously quantified in 3 μL EDTA-plasma by LC-MS/MS in a case-control subgroup of the Leipziger LIFE-Heart Study (N = 911). Confounder analysis with demographic, clinical covariates and serum lipids, cardiac, inflammatory, and hepatic markers were performed. Apos were associated with CAD, CAP, and PAD in a multivariate regression model. ResultsFasting and statin therapy showed strongest effects on apo concentrations. Inverse correlations of HDL-related apos A-I, A-II, A-IV, and C-I were observed for troponin T and interleukin 6. Concentrations of apos A-II, B-100, C-I, and E were decreased under statin therapy. After adjustment for influencing factors and related lipids, only apoB-100 (odds ratio per one SD [OR], 1.39; 95% confidence interval [CI], 1.05–1.84) was independently associated with CAD while apoA-IV (OR, 0.74; 95% CI 0.58–0.95) indicated PAD. ApoB-100 (OR, 1.55; 95% CI, 1.18–2.04), apoC-III (OR, 1.30; 95% CI, 1.06–1.58), and apoE (OR, 1.34; 95% CI, 1.13–1.58) were associated with CAP. ConclusionsTriglyceride rich lipoproteins (TRLs) associated apos A-IV, B-100, C-III, and E are independently associated with stable ASCVD, providing further evidence for a potential role of TRLs in atherogenesis.

Aspirin intake in the morning is associated with suboptimal platelet inhibition, as measured by serum Thromboxane B2, during infarct-prone early-morning hours

Aspirin is traditionally taken once daily in the morning and considered to be effective throughout the 24h interval. Cardiovascular events occur most frequently in the early morning, suggesting that these hours are critical in terms of adequate platelet inhibition. This study therefore assed platelet function in the early morning—8.00 AM—in healthy volunteers, during a once-daily (OD) 80 mg morning in comparison with an OD evening regimen and a twice-daily (BID) 40 mg regimen. It was an open-label randomized cross-over study, comprising 12 healthy subjects. Subjects were allocated to three sequential dosage regimens: 80 mg OD at 8.00 AM, 80mg OD at 8.00 PM, and 40 mg BID at 8.00 AM and PM. Platelet function 12 and 24 hours after aspirin intake was measured by means of serum thromboxane B2 (sTxB2) levels, the collagen/epinephrine closure time (Platelet Function Analyzer(PFA)-200®) and the Aspirin Reaction Units (ARU, VerifyNow®). The results demonstrated that early morning sTxB2 concentrations were 5843pg in the morning regimen, 2877pg in the evening OD regimen, and 3343pg in the BID regimen (morning- vs evening regimen p = < 0.01; morning- vs BID regimen p = < 0.01). Early morning PFA-closure time (p = 0.12)) as well as VerifyNow ARU (p = 0.17) mean values were similar for all three regimens. In conclusion, the OD-morning regimen seems to acquire the lowest level of platelet inhibition during the critical early morning window. Switching to an OD-evening or BID intake seems prudent, although further research on clinical cardiovascular outcome in patients with stable cardiovascular disease is needed.

Radiofrequency catheter ablation prior to percutaneous coronary intervention in patients with atrial fibrillation coexisting with stable coronary artery disease: a single-center pilot study.

Atrial fibrillation (AF) frequently coexists with cardiovascular disease (CAD) in a clinical setting. However, the optimum therapy for AF patients who have concomitant CAD is unclear. We retrospectively examined the efficacy and safety of radiofrequency catheter ablation (RFCA) prior to percutaneous coronary intervention (PCI) in patients with AF who had concomitant stable CAD. Between January 2014 and December 2015, a total 264 patients (179 men; mean age, 65.5 ± 10.1years) who were referred to undergo a first RFCA procedure were reviewed in this study. Of the 264 patients, 41 (15.5%) had stable CAD detected by multi-detector computed tomography before RFCA. Thirty-seven patients who had AF with stable CAD were divided into two treatment arms: (1) RFCA prior to PCI (n = 13) and (2) PCI prior to RFCA (n = 24) [four patients excluded because of left main coronary artery disease (LMCA) or triple vessel disease (TVD)]. The median follow-up was 14 (IQR 8-19) months. There was no significant difference in AF recurrence rate after the procedure between the RFCA first group and PCI first group (P = 0.515). No symptomatic cardiovascular events occurred the during follow-up period. The PCI first group had a significantly longer duration of triple therapy (188.5 ± 167days vs 5.6 ± 24.5days, P = 0.01) and all of the four bleeding events occurred during triple therapy (P = 0.01). The results of this single-center pilot study suggested that prior RFCA in patients with AF coexisting with CAD could have fewer serious bleeding events than prior PCI.

CE1 - Cost-Effectiveness of Rivaroxaban and Aspirin Compared to Aspirin Alone in Patients with Stable Cardiovascular Disease: An Australian Perspective

Abstract Objective In light of the Cardiovascular Outcomes for People using Anticoagulation Strategies (COMPASS) trial, our objective was to assess the cost-effectiveness, from the Australian healthcare perspective, of rivaroxaban in combination with aspirin versus aspirin alone for the prevention of recurrent cardiovascular disease among patients with stable atherosclerotic vascular disease. Methods A Markov model was developed using input data from the COMPASS trial to predict the clinical course and costs of patients over a 20-year time-horizon. The model comprised of three health states: ‘Alive without recurrent CVD’, ‘Alive after recurrent CVD’ and ‘Dead’. Costs were from the Australian public healthcare system perspective, and estimated from published sources, as were utility data. The costs of rivaroxaban were based on current acquisition prices on the Australian Pharmaceutical Benefits Schedule (PBS) and assumed as AUD$3.09/day. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per quality adjusted life year (QALY) gained, and cost per year of life saved (YoLS). Costs and benefits were discounted by 5.0% per year. Results Compared to aspirin alone, rivaroxaban plus aspirin was estimated to cost an additional AUD$12,156 (discounted) per person, but lead to 0.516 YoLS (discounted) and 0.386 QALYs gained (discounted), over 20 years. These equated to ICERs of AUD$23,560/YoLS and AUD$31,436/QALY gained. We have assumed a threshold of AUD$50,000/QALY gained to signify cost-effectiveness. Conclusion Compared to aspirin, rivaroxaban in combination with aspirin is likely to be cost-effective in preventing recurrent cardiovascular events in patients with stable atherosclerotic vascular disease.

Will COMPASS Point to a New Direction in Thrombotic Risk Reduction in Patients With Stable Cardiovascular Disease?

Will COMPASS Point to a New Direction in Thrombotic Risk Reduction in Patients With Stable Cardiovascular Disease?

Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease: Analysis From FOURIER.

The FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) recently showed that the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab significantly reduced major vascular events in patients with stable atherosclerotic cardiovascular disease, including patients with prior myocardial infarction (MI). Within the broad group of patients with prior MI, we hypothesized that readily ascertainable features would identify subsets who derive greater clinical risk reduction with evolocumab. The 22 351 patients with a prior MI were characterized on the basis of time from most recent MI, number of prior MIs, and presence of residual multivessel coronary artery disease (≥40% stenosis in ≥2 large vessels). The relative and absolute risk reductions in major vascular events, including the primary end point (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) and the key secondary end point (cardiovascular death, MI, or stroke), with evolocumab in these subgroups were compared. A total of 8402 patients (38%) were within 2 years of their most recent MI; 5285 patients (24%) had ≥2 prior MIs; and 5618 patients (25%) had residual multivessel coronary artery disease. In a multivariable-adjusted model that simultaneously included all 3 high-risk features and other baseline covariates, more recent MI, multiple prior MIs, and residual multivessel coronary disease remained independent predictors of cardiovascular outcomes, with adjusted hazard ratios (HRs) for the primary end point of 1.37 (95% confidence interval [CI],1.22-1.53), 1.78 (95% CI, 1.59-1.99), and 1.39 (95% CI, 1.24-1.56; all P<0.001). The relative risk reductions with evolocumab for the primary end point tended to be greater in the high-risk subgroups and were 20% (HR, 0.80; 95% CI, 0.71-0.91), 18% (HR, 0.82; 95% CI, 0.72-0.93), and 21% (HR, 0.79; 95% CI, 0.69-0.91) for those with more recent MI, multiple prior MIs, and residual multivessel coronary artery disease, whereas they were 5% (HR, 0.95; 95% CI, 0.85-1.05), 8% (HR, 0.92; 95% CI, 0.84-1.02), and 7% (HR, 0.93; 95% CI, 0.85-1.02) in those without, respectively. Given the higher baseline risk, the respective absolute risk reductions at 3 years exceeded 3% in the high-risk groups (3.4%, 3.7%, and 3.6%) versus ≈1% in the low-risk groups (0.8%, 1.3%, and 1.2%). Patients closer to their most recent MI, with multiple prior MIs, or with residual multivessel coronary artery disease are at high risk for major vascular events and experience substantial risk reductions with low-density lipoprotein cholesterol lowering with evolocumab. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.

Beyond conventional secondary prevention in coronary artery disease-what to choose in the era of CANTOS, COMPASS, FOURIER, ODYSSEY and PEGASUS-TIMI 54? A review on contemporary literature.

Patients with established cardiovascular (CV) disease remain at dramatic residual risk for subsequent events, despite growing evidence in secondary prevention and wider dissemination of intensive treatment. This review focuses on new options in secondary risk prevention as presented by these five major randomized controlled trials (RCT): PEGASUS-TIMI 54, COMPASS, FOURIER, ODYSSEY and CANTOS. Three main therapeutic targets are addressed: residual cholesterol, residual inflammatory and residual thrombotic risk. All of the trials reviewed included patients with stable CV disease on optimal medical treatment with a surprising similar mortality. As of now, evolocumab, alirocumab and ticagrelor are on the market, while rivaroxaban and canakinumab are not yet licensed for the treatment of secondary prevention in CV disease. Although life-style modifications and better utilization of established medical treatment options will remain first-line strategy, new medication is just about to enter the market. Secondary prevention in coronary artery disease (CAD) holds a strong potential to reduce subsequent CV events, even CV death. It seems that a combination of an aggressive lipid-lowering treatment in combination with antithrombotic therapy could improve prognosis significantly (at least for distinct subgroups). Against this background, individual efficacy, risk, and costs have to be considered when identifying patients for each new regime.