post-ACS Patients Research Articles

Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers: A Randomized Crossover Study

ObjectivesThe study sought to assess whether treatment with ticagrelor, as compared with prasugrel and clopidogrel, improves endothelium-dependent dilation throughout the course of the treatment and other vascular biomarkers, including systemic adenosine plasma levels. BackgroundThe in vivo off-target effects of ticagrelor in post–acute coronary syndrome (ACS) patients remain poorly characterized. MethodsFifty-four stable post-ACS patients were sequentially exposed to each of the 3 oral P2Y12 inhibitors following a 3-period balanced Latin square crossover design with 4 weeks per treatment in 5 European centers. The primary endpoint was the assessment of endothelial function with pulse amplitude tonometry and expressed as reactive hyperemia index at treatment steady state. Secondary endpoints included reactive hyperemia index after loading or before maintenance regimen, systemic adenosine plasma levels, a wide set of vascular biomarkers, and ticagrelor or AR-C124910XX plasma levels throughout each ticagrelor period. In 9 patients, the evaluation of endothelial function was performed simultaneously by pulse amplitude tonometry and flow-mediated dilation. ResultsReactive hyperemia index did not differ after ticagrelor (1.970 ± 0.535) as compared with prasugrel (2.007 ± 0.640; p = 0.557) or clopidogrel (2.072 ± 0.646; p = 0.685), nor did systemic adenosine plasma levels or vascular biomarkers at any time points. P2Y12 platelet reactivity units were lower after ticagrelor as compared with clopidogrel at all time points and after maintenance dose as compared with prasugrel. Flow-mediated dilation did not differ after the maintenance dose of ticagrelor as compared with clopidogrel and prasugrel. ConclusionsTicagrelor did not improve endothelial function or increased systemic adenosine plasma levels as compared with prasugrel and clopidogrel in stabilized patients who suffered from an ACS. (Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans [HI-TECH]; NCT02587260).

Incidence, timing, and type of first and recurrent ischemic events in patients with and without peripheral artery disease after an acute coronary syndrome

BackgroundPatients with peripheral artery disease (PAD) are known to have an increased risk of ischemic cardiovascular events. However, the influence of concomitant PAD on first and subsequent recurrent ischemic events after an acute coronary syndrome (ACS) remains poorly characterized. MethodsWe analyzed the combined data set from 4 randomized trials (PLATO, APPRAISE-2, TRA-CER, and TRILOGY ACS) in ACS for a follow-up length of 1 year. Using multivariable regression, we examined the association between PAD and major adverse cardiovascular events, a composite of cardiovascular death, myocardial infarction, and stroke. Among patients with a nonfatal first event, we evaluated the incidence and type of a second recurrent event. ResultsA total of 4,098 of 48,094 (8.5%) post-ACS patients had a history of PAD. The unadjusted frequency of major adverse cardiovascular events was 2-fold higher in patients with PAD (14.3% vs 7.5%) over a median (25th-75th) follow-up of 353 (223-365) days with an adjusted hazard ratio of 1.63 (95% CI: 1.48-1.78; P < .001). The frequency of recurrent ischemic events among those patients with a first, nonfatal event was higher among those with PAD (40.0% vs 27.7%). The relative frequency of each event type (cardiovascular death, noncardiovascular death, myocardial infarction, or stroke) within first and subsequent ischemic events was similar regardless of PAD status at baseline. ConclusionsPatients with PAD have a significantly higher risk of first and recurrent ischemic events in the post-ACS setting. These findings highlight the opportunity for improved treatments in patients with PAD who experience an ACS.

In-hospital prescriptions of secondary-prevention medications for post-acute coronary syndrome patients in South Korea .

Optimal medical therapy and the management of cardiac risk factors are crucial for the secondary prevention of acute coronary syndrome (ACS). However, there have been reports on the underutilization of secondary-prevention medications for ACS. This study aimed to investigate adherence of in-hospital prescriptions to clinical practice guidelines for the secondary prevention of ACS using real-world data. We collected information on ACS patients from national insurance claims data. The in-hospital prescriptions of secondary-prevention medications for post-ACS patients were analyzed. Prescription patterns were analyzed in relation to demographic, clinical, and institutional features. The utilization of five recommended medications and the factors influencing their use were investigated using logistic regression analysis. In total, 1,983 ACS patients were included in this analysis. The prescription rates of secondary-prevention medications were 94.4% for aspirin, 96.1% for P2Y12 inhibitors, 67.4% for β-blockers, 63.5% for ACE inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and 86.5% for statins. Less than half of the patients were prescribed all five recommended medications. The prescription rate of secondary-prevention medications was lower in patients with unstable angina than in patients with myocardial infarction, particularly for β-blockers and ACEIs/ARBs. The best predictive variable for determining the use of all five recommended medications was the type of ACS according to the results of the logistic regression analysis. In Korea, there is room for improvement in the prescription rates of secondary-prevention medications in post-ACS patients, particularly for β-blockers and ACEIs/ARBs. .

Diagnostic Accuracy of Screening Tests and Treatment for Post-Acute Coronary Syndrome Depression: A Systematic Review.

Patients who have had an acute coronary syndrome (ACS) event have an increased risk for depression. To evaluate the diagnostic accuracy of depression screening instruments and to compare safety and effectiveness of depression treatments in adults within 3 months of an ACS event. MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane Database of Systematic Reviews from January 2003 to August 2017, and a manual search of citations from key primary and review articles. English-language studies of post-ACS patients that evaluated the diagnostic accuracy of depression screening tools or compared the safety and effectiveness of a broad range of pharmacologic and nonpharmacologic depression treatments. 2 investigators independently screened each article for inclusion; abstracted the data; and rated the quality, applicability, and strength of evidence. Evidence from 6 of the 10 included studies showed that a range of depression screening instruments produces acceptable levels of diagnostic sensitivity, specificity, and negative predictive values (70% to 100%) but low positive predictive values (below 50%). The Beck Depression Inventory-II was the most studied tool. A large study found that a combination of cognitive behavioral therapy (CBT) and antidepressant medication improved depression symptoms, mental health-related function, and overall life satisfaction more than usual care. Few studies, no evaluation of the influence of screening on clinical outcomes, and no studies addressing several clinical interventions of interest. Depression screening instruments produce diagnostic accuracy metrics that are similar in post-ACS patients and other clinical populations. Depression interventions have an uncertain effect on cardiovascular outcomes, but CBT combined with antidepressant medication produces modest improvement in psychosocial outcomes. Agency for Healthcare Research and Quality (PROSPERO: CRD42016047032).

The prognostic utility of dihomo-gamma-linolenic acid (DGLA) in patients with acute coronary heart disease

BackgroundWe previously investigated the prognostic utility of red blood cell (RBC) n-3 fatty acids (FAs) in survivors of an acute myocardial syndrome (ACS) but found no relationship with all-cause mortality and cardiac death or MI after two years. Here we extend our follow-up to 7years, focusing on the potential predictive power of RBC n-6 FAs. MethodsWe included 398 ACS patients presenting with increased troponin-T (TnT) levels for whom baseline RBC FA data were available. Cox regression analysis was used to relate the risk of future events to RBC n-6 FA levels, both continuously and by quartile. ResultsAt 7-year follow-up, 183 (46.0%) had died, 128 (32.2%) had experienced another MI and 24 (6.0%) had had a stroke. Death or MI occurred in 227 patients (57.0%); and death, MI or stroke in 235 patients (59.0%). In a multivariable Cox regression model for total death, the hazard ratio (HR) in the highest as compared to the lowest quartile of dihomo-γ-linolenic acid (DGLA) was 0.55 [95% confidence interval (CI), 0.35–0.88, p=0.012, for death or MI [HR 0.62 (95% CI, 0.41–0.94), p=0.025], and for the fully combined endpoint [HR 0.57 (95% CI, 0.38–0.86), p=0.006]. Similar results were found in the per 1-SD analysis. No other RBC n-6 FAs significantly predicted these outcomes in multivariable models. ConclusionRBC DGLA levels had significant independent prognostic value in post-ACS patients. These findings need confirmation, and the possible biochemical pathways by which higher DGLA membrane levels may be cardioprotective should be explored.

Quel dépistage de l’ischémie myocardique après angioplastie dans le syndrome coronaire aigu ?

Unstable coronary artery disease is a more aggressive condition than stable coronary artery disease, accounting for the high incidence of major adverse cardiovascular events following acute coronary syndromes (ACS), which includes the need for iterative repeat revascularization. The aim of myocardial ischemia screening in post-ACS patients is to detect this unfavourable evolution (either on initial culprit or non culprit lesions) and to prevent any clinical complication. Although there is no strict recommendation in this particular situation, screening should be based on the use of stress imaging techniques. The optimal timing and frequency for testing will depend on the clinical characteristics of the patients and the coronary revascularization procedure features.

Rationale and design of the Hunting for the off-target propertIes of Ticagrelor on Endothelial function and other Circulating biomarkers in Humans (HI-TECH) trial

Among the 3 approved oral P2Y12 inhibitors for the treatment for patients with acute coronary syndrome (ACS), ticagrelor, but not prasugrel or clopidogrel, has been associated with off-target properties, such as improved endothelial-dependent vasomotion and increased adenosine plasma levels. The HI-TECH study (NCT02587260) is a multinational, randomized, open-label, crossover study with a Latin squares design, conducted at 5 European sites, in which patients free from recurrent ischemic or bleeding events ≥30 days after a qualifying ACS were allocated to sequentially receive a 30 ± 5-day treatment with prasugrel, clopidogrel, and ticagrelor in random order. The primary objective was to evaluate whether ticagrelor, at treatment steady state (ie, after 30 ± 5 days of drug administration), as compared with both clopidogrel and prasugrel, is associated with an improved endothelial function, assessed with peripheral arterial tonometry. Thirty-six patients undergoing evaluable endothelial function assessment for each of the assigned P2Y12 inhibitor were needed to provide 90% power to detect a 10% relative change of the reactive hyperemia index in the ticagrelor group. The HI-TECH study is the first randomized, crossover study aiming to ascertain whether ticagrelor, when administered at approved regimen in post-ACS patients, improves endothelial function as compared with both clopidogrel and prasugrel.

Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention

BackgroundEzetimibe improves cardiovascular (CV) outcomes in patients stabilized after acute coronary syndrome (ACS) when added to statin therapy. After ACS, patients vary considerably in their risk for recurrent CV events. ObjectivesThis study tested the hypothesis that atherothrombotic risk stratification may be useful to identify post-ACS patients who have the greatest potential for benefit from the addition of ezetimibe to statin therapy. MethodsThe TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention (TRS 2°P) is a simple 9-point risk stratification tool, previously developed in a large population with atherothrombosis to predict CV death, myocardial infarction (MI), and ischemic stroke (CV death/MI/ischemic cerebrovascular accident [iCVA]). The current study applied this tool prospectively to 17,717 post-ACS patients randomized either to ezetimibe and simvastatin or to placebo and simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Treatment efficacy was assessed by baseline risk for CV death/MI/iCVA, the IMPROVE-IT composite endpoints (CE), and individual component endpoints at 7 years. ResultsAll 9 clinical variables in the TRS 2°P were independent risk indicators for CV death/MI/iCVA (p < 0.001). The integer-based scheme showed a strong graded relationship with the rate of CV death/MI/iCVA, the trial CE, and the individual components (p trend <0.0001 for each). High-risk patients (n = 4,393; 25%), defined by ≥3 risk indicators, had a 6.3% (95% confidence interval: 2.9% to 9.7%) absolute risk reduction in CV death/MI/iCVA at 7 years with ezetimibe/simvastatin, thus translating to a number-needed-to-treat of 16. Intermediate-risk patients (2 risk indicators; n = 5,292; 30%) had a 2.2% (95% confidence interval: −0.3% to 4.6%) absolute risk reduction. Low-risk patients (0 to 1 risk indicators; n = 8,032; 45%) did not appear to derive benefit from the addition of ezetimibe (p interaction = 0.010). Similar findings were observed for the IMPROVE-IT primary CE. ConclusionsAtherothrombotic risk stratification using the TRS 2°P identifies high-risk patients who derive greatest benefit from the addition of ezetimibe to statin therapy for secondary prevention after ACS. (Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878)

A study of drug utilization pattern in post-acute coronary syndrome (ACS) patients at tertiary care teaching hospital: a prospective unicentric study

Background: The main objective of drug utilization research is to assess the rationality of drug use for specific disease. Long term survival in post-ACS patients depends largely on how well post ACS period is managed. Our aim is to record drug utilization pattern in post ACS patients after discharge and during follow-up visits.Methods: Prospective unicentric study was conducted in 200 patients suffering from ACS at Cardiology OPD of GCS Medical College, Hospital and Research Centre, Ahmedabad. Prescriptions issued to study subjects at the time of discharge and during follow-up who had recently suffered from ACS were intercepted after consultation and data recorded as per WHO guidelines as how to investigate drug use. Data were collected in the structured proforma (Case Record Form-CRF) which includes patient’s demographic details, registration number, diagnosis and the drug prescribed. Each prescription was analyzed using WHO core prescribing indicators to evaluate the rationality of the prescriptions.Results: Out of 200, 104 (52%) suffered from unstable angina, 84(42%) suffered from STEMI and 12(6%) were suffered with NSTEMI. Male patients of 114(57%) were more prone to ACS than female patients of 86 (43%). Out of 200 patients, 193 (97%) received antiplatelet, 187 (94%) received antihypertensive, 184 (92%) received anticoagulants, 180 (90%) received lipid lowering drugs and 119 (60%) received Nitrates. As per WHO core prescribing indicators, the average number of drugs encountered per prescription was 7.96. The prescription showed a high usage of drugs from NLEM i.e. 72.20% in post-ACS patients. However the percentage of drugs prescribed by generic name was only 10.68%. The frequency of use of injectable preparations in post-ACS patients was found to be 17.84% which was in accordance with WHO reference value. Out of 17.84% injectable preparations, only 0.82% accounted for antibiotic injection.Conclusions: Although generic prescribing indicator shows a low range of usage, it is interesting to notice that prescription pattern has a high usage of drugs from NLEM (78.2%) in ACS. Thus present study provides valuable insight about the overall pattern of drugs used in post-Acute Coronary syndrome.

The post-ACS patient: shared care to improve outcomes

The post-ACS patient: shared care to improve outcomes

LIFE QUALITY OF PATIENTS ACCORDING TO GENDER AND THE FORM OF NON-ST-ELEVATION ACUTE CORONARY SYNDROME

Aim . To assess the specifics of psychoemotional state of adult patients with non ST elevation acute coronary syndrome (NSTEACS) in 6 months post hospitalization. Material and methods. Totally, 101 patient included, with non-obstructive lesion of coronary flow. Groups were formed by gender: group 1 — 51 females, group 2 — 50 males. Mean age: women 50,5±4,7 y. o., men 46,7±6,8 y. o. Patients were also selected to subgroups by NSTEACS type: subgroup A — unstable angina (UA), subgroup B — myocardial infarction. Patients were questionned by phone in 6 months after discharge. The questionnaire included key points about health, emotional balance, physical activity and life quality. Results . There are gender differences in life quality constituents between men and women. In questions on general health state 6% of women replied that are not satisfied with their health, in men — 2%; satisfactorily graded their health state 27% of women and 38% of men, good — 47% and 46%, excellent — 20% and 14%, respectively. Pre-morbid physical activity at work was saved in 45% of men and 32% of women; active life style retained 47% of women and 42% of men. Men more often felt hopelessness (43% and 12%; p 0,05) and were unsatisfied with their psychological state (31% and 6%; p 0,05), however men noted loss of interest to former habits (13% и 22%; р>0,05). The specifics in subtypes of NSTEACS was also noted. Conclusion . Regardless an individuality of the meanings of life quality, experiences, coping, there is gender specifics, as specifics in NSTEACS subtype. The specifics can be included as a part of patient-centered work with post-ACS patients.

On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT)

We aimed to determine the efficacy and safety of adding ezetimibe (Ez) to simvastatin (S) in a post-acute coronary syndrome (ACS) population in a prespecified on-treatment analysis. We evaluated 17,706 post-ACS patients from the IMPROVE-IT trial who had low-density lipoprotein cholesterol values between 50 and 125 mg/dL and who received Ez 10 mg/d with S 40 mg/d (Ez/S) or placebo with simvastatin 40 mg/d (P/S). The primary composite end point was cardiovascular death, myocardial infarction, unstable angina, coronary revascularization ≥30 days postrandomization, or stroke. The on-treatment analysis included patients who received study drug for the duration of the trial or experienced a primary end point or noncardiovascular death within 30 days of drug discontinuation. Mean low-density lipoprotein cholesterol values at 1 year were 71 mg/dL for P/S and 54 mg/dL for Ez/S (absolute difference -17 mg/dL = -24%; P < .001). The 7-year Kaplan-Meier estimate of the primary end point occurred in 32.4% in the P/S arm and 29.8% in the Ez/S arm (absolute difference 2.6%; HRadj 0.92 [95% CI 0.87-0.98]; P = .01). The absolute treatment effect favoring Ez/S was 30% greater than in the intention-to-treat analysis of IMPROVE-IT. This analysis provides additional support for the efficacy and safety of adding Ez to S in this high-risk, post-ACS population.

The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial.

To examine the efficacy and safety of ezetimibe added to statin in patients with prior coronary artery bypass graft surgery (CABG) following hospitalization for an acute coronary syndrome (ACS). In the IMPROVE-IT trial, post-ACS patients with mean low density lipoprotein cholesterol (LDL-C) of 93.8 mg/dL at presentation were randomized to simvastatin/ezetimibe or simvastatin/placebo. The primary endpoint was cardiovascular death, major coronary event or stroke, and the median follow-up was 6 years. Efficacy and safety endpoints were examined by prior CABG status. Among 18 134 patients, 1684 (9.3%) had a prior CABG (median age 69 years, 82% male). During the trial, the median time-weighted LDL-C level was 55.0 mg/dL with simvastatin/ezetimibe vs. 69.9 mg/dL with simvastatin/placebo in patients with prior CABG (P < 0.001), and it was 53.6 mg/dL vs. 69.5 mg/dL, respectively, in patients without prior CABG (P < 0.001). The rate of the primary endpoint was higher in patients with vs. without prior CABG [56% vs. 32%, adj. hazard ratio 1.45, 95% confidence interval (CI) 1.33-1.58]. Patients with prior CABG receiving simvastatin/ezetimibe had an 8.8% (95% CI 3.1-14.6%) lower absolute risk over simvastatin/placebo in the primary endpoint, whereas patients without prior CABG had a 1.3% (95% CI 0-2.6%) lower absolute risk (P-interaction = 0.02). There were no between-group significant differences in safety endpoints. The clinical benefit of adding ezetimibe to statin appears to be enhanced in patients with prior CABG, supporting the use of intensive lipid lowering therapy in these high-risk patients following ACS.

Diabetes mellitus, glucose control parameters and platelet reactivity in ticagrelor treated patients

IntroductionDespite the recent advances, prognostic difference between diabetic and non diabetic patients is still marked after an acute coronary syndrome. Diabetes mellitus and poor glycemic control represent well established pro-thrombotic conditions, as inadequate glycemic control can lead to impaired responsiveness to antiplatelet therapies. Among new antiplatelet agents, ticagrelor has provided more potent platelet inhibition, potentially offering benefits in reducing residual high-on treatment platelet reactivity. However, no study has so far investigated the relationship between diabetes mellitus and platelet reactivity in patients treated with ticagrelor after an acute coronary syndrome (ACS). MethodsIn patients treated with acetylsalicylic acid (100–160mg) and ticagrelor (90mg twice a day) platelet reactivity was assessed at 30–90days post-discharge for an ACS. Diabetic status was defined before discharge. Multiple-electrode aggregometry was used to assess platelet function. High residual platelet reactivity was defined as ADP-test results >417AU∗min. ResultsDiabetes was observed in 86 out of 224 patients (38.4%). Diabetes was significantly associated with older age, higher BMI, renal failure, hypertension, treatment with diuretics, higher levels of WBC, glycaemia, HbA1c, and lower levels of HDL-cholesterol. Platelet reactivity was higher in diabetic patients as compared to non-diabetic ones for all the different activating stimuli tested. A total of 29 patients (12.9%) displayed high-residual platelet reactivity with ticagrelor with an almost double rate in diabetics as compared to non-diabetics (18.8% vs 9.4%, p=0.06; adjusted OR[95%CI]=2.12[1.1–4.1], p=0.025). A progressive increase of platelet reactivity was observed for higher HbA1c levels (r=0.15, p=0.029). ConclusionThe present study shows that diabetic patients display higher platelet reactivity despite dual antiplatelet therapy. In fact, diabetes mellitus emerged as independent predictor of high-residual platelet reactivity in post-ACS patients treated with ticagrelor.

Lower Methylation of the ANGPTL2 Gene in Leukocytes from Post-Acute Coronary Syndrome Patients.

DNA methylation is believed to regulate gene expression during adulthood in response to the constant changes in environment. The methylome is therefore proposed to be a biomarker of health through age. ANGPTL2 is a circulating pro-inflammatory protein that increases with age and prematurely in patients with coronary artery diseases; integrating the methylation pattern of the promoter may help differentiate age- vs. disease-related change in its expression. We believe that in a pro-inflammatory environment, ANGPTL2 is differentially methylated, regulating ANGPTL2 expression. To test this hypothesis we investigated the changes in promoter methylation of ANGPTL2 gene in leukocytes from patients suffering from post-acute coronary syndrome (ACS). DNA was extracted from circulating leukocytes of post-ACS patients with cardiovascular risk factors and from healthy young and age-matched controls. Methylation sites (CpGs) found in the ANGPTL2 gene were targeted for specific DNA methylation quantification. The functionality of ANGPTL2 methylation was assessed by an in vitro luciferase assay. In post-ACS patients, C-reactive protein and ANGPTL2 circulating levels increased significantly when compared to healthy controls. Decreased methylation of specific CpGs were found in the promoter of ANGPTL2 and allowed to discriminate age vs. disease associated methylation. In vitro DNA methylation of specific CpG lead to inhibition of ANGPTL2 promoter activity. Reduced leukocyte DNA methylation in the promoter region of ANGPTL2 is associated with the pro-inflammatory environment that characterizes patients with post-ACS differently from age-matched healthy controls. Methylation of different CpGs in ANGPTL2 gene may prove to be a reliable biomarker of coronary disease.

SUCCESS OF MEDICAL EDUCATION ON ACS MANAGEMENT: FOCUS ON ADHERENCE TO ANTIPLATELET THERAPY POST-DISCHARGE AND REDUCING HOSPITAL READMISSIONS

Hospital readmissions for acute coronary syndrome (ACS) are preventable, yet 48% of Americans who survive a new coronary event will have a recurrent event that potentially warrants readmission.[1] This common and costly occurrence has prompted leaders in quality care (ie, National Quality Forum, Centers for Medicare and Medicaid Services, and Agency for Healthcare Research and Quality) to mandate improved quality of care specifically for these patients.[2] Both hospital readmissions and suboptimal use of guideline-recommended antiplatelet regimens post-ACS event have been identified as areas needing improvement.[2,3] We sought to determine if online continuing medical education (CME) could improve the knowledge, competence, and clinical decision making of cardiologists and primary care physicians (PCPs) related to post-ACS patient medication adherence and hospital readmission.

Ischemic cardiac outcomes and hospitalizations according to prior macrovascular disease status in patients with type 2 diabetes and recent acute coronary syndrome from the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care trial

Concerns raised regarding adverse cardiovascular (CV) outcomes with new therapies for type 2 diabetes mellitus (T2DM) have led to several large-scale CV outcome trials. The EXAMINE trial confirmed noninferiority of the dipeptidyl dipeptidase 4 inhibitor alogliptin to placebo on major adverse cardiac event rates in a post-acute coronary syndrome (ACS) T2DM population. We present data on additional ischemic cardiac events and CV hospitalizations in EXAMINE. Patients with T2DM and an ACS event in the previous 15 to 90 days were randomly assigned to alogliptin or placebo on a background of standard treatment for diabetes. The incident rates of a 5-component composite end point of CV death, stroke, myocardial infarction, unstable angina, and coronary revascularization as well as CV hospitalization were calculated in all participants and according to macrovascular disease at baseline. There were no significant differences between alogliptin (n = 2,701) and placebo (n = 2,679) in the event rate of the 5-component composite endpoint with median follow-up 533 days (21.0% vs 21.5%, hazard ratio [HR] 0.98 [0.87-1.10], P = .72). No differences were observed in terms of CV hospitalization (25.0% vs 25.4%, HR 0.98 [0.88-1.09], P = .70) or coronary revascularization (10.6% vs 10.2%, HR 1.05 [0.88-1.09], P = .60). No interactions were observed for treatment and prior macrovascular disease. EXAMINE demonstrates that there was no increase in the risk of cardiac ischemic events and CV hospitalizations with alogliptin in a high-risk post-ACS patient population. Because these are major driver of overall health care costs, these data suggest that there would be no adverse impact on health care resource utilization.

Effects of Optimism and Gratitude on Physical Activity, Biomarkers, and Readmissions After an Acute Coronary Syndrome: The Gratitude Research in Acute Coronary Events Study.

Positive psychological constructs, such as optimism, are associated with beneficial health outcomes. However, no study has separately examined the effects of multiple positive psychological constructs on behavioral, biological, and clinical outcomes after an acute coronary syndrome (ACS). Accordingly, we aimed to investigate associations of baseline optimism and gratitude with subsequent physical activity, prognostic biomarkers, and cardiac rehospitalizations in post-ACS patients. Participants were enrolled during admission for ACS and underwent assessments at baseline (2 weeks post-ACS) and follow-up (6 months later). Associations between baseline positive psychological constructs and subsequent physical activity/biomarkers were analyzed using multivariable linear regression. Associations between baseline positive constructs and 6-month rehospitalizations were assessed via multivariable Cox regression. Overall, 164 participants enrolled and completed the baseline 2-week assessments. Baseline optimism was significantly associated with greater physical activity at 6 months (n=153; β=102.5; 95% confidence interval, 13.6-191.5; P=0.024), controlling for baseline activity and sociodemographic, medical, and negative psychological covariates. Baseline optimism was also associated with lower rates of cardiac readmissions at 6 months (n=164), controlling for age, sex, and medical comorbidity (hazard ratio, 0.92; 95% confidence interval, [0.86-0.98]; P=0.006). There were no significant relationships between optimism and biomarkers. Gratitude was minimally associated with post-ACS outcomes. Post-ACS optimism, but not gratitude, was prospectively and independently associated with superior physical activity and fewer cardiac readmissions. Whether interventions that target optimism can successfully increase optimism or improve cardiovascular outcomes in post-ACS patients is not yet known, but can be tested in future studies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01709669.

Abstract 19694: Reduction in Non-hemorrhagic Stroke With Ezetimibe/Simvastatin Compared With Simvastatin Alone in the IMPROVE-IT Trial

Background: Statins have been demonstrated to reduce ischemic stroke. Intensive therapy with ezetimibe/simvastatin (E/S) in IMPROVE-IT significantly reduced the occurrence of cardiovascular events in patients post ACS compared to placebo/simvastatin (S). We evaluated the effect of E/S vs S on stroke outcomes. Methods: We determined the KM-rate of stroke, by type,during the median 6 year follow-up in 18,144 patients treated with E/S vs S in the IMPROVE-IT trial. Stroke was adjudicated and divided into non-hemorrhagic (NH), hemorrhagic (H), or unknown (U) by a blinded clinical event committee. Stroke reductions were adjusted to absolute change in LDL-C for comparison to prior studies. Results: There were 641 (3.5%) subjects with stroke during follow up, including 533 non-hemorrhagic, 102 hemorrhagic, and 14 unknown strokes. Overall, stroke tended to be reduced with E/S (4.2 vs 4.8%; HR 0.86, CI 0.73-1.00, p=0.052), with a significant reduction of NH stroke (3.4 vs 4.1%; HR 0.79, CI 0.67-0.94, p=0.008, Figure), but a numerical increase in H stroke (0.8 vs 0.6%; HR 1.38, CI 0.93-2.04, p=0.11, Figure). Results were similar when NH/U strokes were combined. When adjusted for LDL reduction, the NH stroke reduction appears to be similar to greater than the extent previously reported with statin therapy alone (figure). Reductions in NH strokes were consistent across major demographic and lipid subgroups. Of note, in 1071 patients with prior stroke or TIA, a known high-risk group, the absolute benefit of E/S was particularly marked for NH strokes; 9.9vs 14.7% (HR 0.61 (0.41-0.91, NNT 21), though benefit remained in those without prior stroke 3.1 vs 3.5% (HR 0.84, CI 0.70-1.01, NNT 250, Pint=0.16). No difference in hemorrhagic stroke was noted in either group. Conclusions: Lipid lowering therapy with E/S was superior to S in the incidence of non-hemorrhagic stroke through a median of 6 years; there was a large absolute benefit in patients with prior stroke or TIA.

Non-clinical development of CER-001.

Cardiovascular disease remains the most pressing healthcare issue for the developed world and is becoming so for developing countries. There are no currently approved therapies that can rapidly reduce the burden of unstable, inflamed plaque in the overall coronary vascular bed. High-density lipoprotein (HDL) has multiple actions that could lead to plaque stabilization, such as rapid removal of large quantities of cholesterol from the vasculature through the process of reverse lipid transport, improvement in endothelial function, protection against oxidative damage, and reduction in inflammation. Short-term infusion of HDL-mimetics in animal models as well as in humans has shown promising effects on the plaque size and morphology. Cerenis Therapeutics has developed CER-001, a negatively charged lipoprotein complex consisting of phospholipid and recombinant human apoA-I that mimics the structure and function of natural HDL. Three clinical trials using CER-001 infusions have demonstrated improvements in the carotid wall thickness of patients with familial hypercholesterolaemia and in patients with hypo-alphalipoproteinaemia, as well as an impact on coronary plaque burden measured by intravascular ultrasonography at the lowest tested dose (3 mg/kg) in post-ACS patients. Here, we reviewed the non-clinical data leading to the demonstration that CER-001 is a full HDL mimetic.