Index Acute Coronary Syndrome Event Research Articles

Evaluation of Clinical Features including the frequency of Familial Hypercholesterolemia, and 2-Year Cardiovascular Outcomes in Patients with Early Acute Coronary Syndrome: Real-Life Data from a Retrospective Cohort

Objective: This retrospective study, based on real-life data, aimed to evaluate the clinical characteristics and 2-year cardiovascular outcomes in patients presenting with early acute coronary syndrome (ACS) in a tertiary healthcare center. Methods: Information including at least 2-year endpoint data after index ACS event was retrieved from hospital records. Age limit for early ACS was considered <55 years for males and <60 years for females. Results: Of 985 consecutive ACS patients (770 males; age range, 21-93 years) 361 (36.6%) met early ACS criteria. Frequency familial hypercholesterolemia (FH) was 7.6% and higher in the young-age group (15.5%) than in the old-age group (3%) (p<0.001). During the follow-up (30 monts), the risk predictors for cardiovascular events were the index event being ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction and the presence of hypertension, and the risk predictors for mortality were female sex, older age, in-hospital cardiovascular complications. Conclusion: A very high rate of early ACS (36.6%) was observed in this retrospective ACS cohort of a single center from Turkey. Compared to older patients, young patients were more smoking, more obese, less diabetic, and less hypertensive. High total cholesterol, high triglycerides, low HDL-cholesterol levels, high non-HDL cholesterol, family history of CAD, and FH were also more commonly observed in the young group. High FH prevalence might be a major factor of the high prevalence of premature ACS in this population. Both the in-hospital and 2-year follow-up mortality rates were significantly lower in the old-age group.

Lipid-Lowering Therapy Utilization and Dosage Among Patients with Acute Coronary Syndrome Events: A Retrospective Cohort from 12 Community Hospitals.

Clinical practice guidelines recommend initiating a high-intensity LLT and continued monitoring of low-density lipoprotein cholesterol (LDL-C) following acute coronary syndrome (ACS). We used real-world data to describe LLT utilization after discharge and 1-year adherence. The reduction in LDL-C was also evaluated. Data were extracted from electronic health records (EHRs) from 12 hospitals in a large community healthcare system in midwestern United States between 2013 and 2019. Data on eligible patients recently discharged with an ACS event were linked to pharmacy claims data to describe LLT fill rates and 1-year post-discharge adherence. Adherence was reported as the proportion of days covered ≥80%. Of the 10,589 eligible patients, 49% filled a high-intensity statin at discharge and only 36% were adherent at 1 year. The mean (SD) age was 66.1±13.3, 39.3% were females, 58.8% were Caucasian, and 53.0% had Medicare. There was a clear trend for greater fill rates at discharge among patients with higher LDL-C values than those with lower values (p<0.01). Key predictors of high-intensity (versus medium-intensity) LLT use within 21 days after an ACS event included ACS type (odds ratio [OR] 0.59; 95% confidence interval [CI] 0.52-0.67 for NSTEMI versus STEMI), age group (OR: 0.59; 95% CI: 0.48-0.72 for >75 years versus <65years), and statin use before index ACS event (OR: 1.56; 95% CI: 1.23-1.88). This real-world study found that despite recommendations in clinical practice guidelines, high-intensity LLT fill rates at discharge and 1-year adherence to LLT remain suboptimal. Clinical characteristics, including ACS type and LDL-C values, were strong predictors of filling and adherence to guideline-recommended therapy. Age, sex, and race/ethnicity disparities were observed in discharge fill rates and 1-year adherence. These results highlight the need for continued efforts at the patient and provider levels to improve LLT adherence among ACS patients.

Strokes and Transient Ischemic Attacks Occurrence During Annual Dual Antiplatelet Therapy.

The incidence of stroke/TIA during annual dual antiplatelet therapy (ADAPT) for acute coronary syndrome (ACS) remains high. Some evidence suggests that shorter than ADAPT may diminish such risk, still providing adequate vascular protection. However, the precise timing of strokes/TIA occurrences during ADAPT is unclear but may be important for determining optimal preventive treatment duration. The precise timing of secondary cerebrovascular events over ADAPT. Access was gained to the FDA-issued Platelet Inhibition and Outcomes (PLATO) trial data set on which post hoc analyses of stroke/TIA timing after ticagrelor and clopidogrel on top of aspirin was explored. Events were counted and plotted over time from day 1 till day 365 after the index ACS event. Among 18,624 enrollees, 252 strokes and 49 TIAs were reported. After the exclusion of entries with missing dates, unclear randomization codes, and events beyond 1-year follow-up, 238 strokes and 45 TIAs were analyzed. Overall, most frequent strokes/TIAs occurred within the first day after qualifying ACS, with the gradual declines after day 7 and day 40 reaching background counts thereafter. The strokes/TIAs patterns did not differ much between P 2 Y12 inhibitors except for twice more events at day 1 and excess exclusions after day 365 in the ticagrelor arm. Most cerebrovascular events emerged very early after ACS despite ADAPT. This large hypothesis-generating evidence may justify shorter than the ADAPT duration after ACS. Twice more events at day 1 and excess late ticagrelor exclusions in PLATO deserve further scrutiny. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00391872.

Abstract 12605: Sex Differences in Cardiovascular Revascularization Strategies and Outcomes in Dialysis Patients

Background: Coronary artery disease is the leading cause of mortality in patients with kidney failure. Little is known about sex differences in revascularization strategies and the associated risk of death in dialysis patients. Methods: We evaluated 60,492 patients who initiated dialysis between 1/1/2005 and 12/31/2018 and had at least one hospitalization with a primary diagnosis of an acute coronary syndrome (ACS), using the United States Renal Data System with linked Medicare claims, we examined the association of sex with initial cardiac revascularization (defined as coronary artery bypass graft [CABG], percutaneous coronary intervention [PCI], or both on the same day) within 30 days of the first ACS hospitalization using adjusted multinomial regression, and the association of sex and initial cardiac revascularization on the outcomes of all-cause death and myocardial infarction using adjusted time-to-event models. Results: The mean age of patients at index ACS hospitalization was 72±11 years, and 40.4% were women. Overall, 40.5% received PCI, 20.8% received CABG, and 6.1% received both CABG and PCI. After an index ACS event, as compared to no revascularization, women as compared to men had a 41% lower likelihood of receiving CABG (OR, 0.59; 95% CI, 0.56-0.62), 13% lower likelihood of receiving PCI (OR, 1.48; 95% CI, 1.42-1.55), and 41% lower likelihood of receiving CABG and PCI (OR, 0.59; 95% CI, 0.55-0.64). Women had a slightly lower risk of all-cause death during the follow-up period than men without treatment (HR, 0.87; 95% CI, 0.85-0.90) or after receiving PCI (HR, 0.94; 95% CI, 0.90-0.97), but no difference in all-cause death after receiving CABG, and after receiving both CABG and PCI. Women had a higher risk of having MI after receiving CABG (HR, 1.12; 95% CI, 1.05-1.19), and a lower risk of MI after receiving PCI. Conclusion: Among patients undergoing dialysis with ACS, women receive less treatment with CABG or PCI than men. Women have a lower adjusted risk of all-cause mortality with PCI, a lower risk of MI after PCI, and a higher adjusted risk of MI with CABG, as compared to men. Revascularization strategies for CV disease may need to be modified based on sex.

Event Rates and Risk Factors for Recurrent Cardiovascular Events and Mortality in a Contemporary Post Acute Coronary Syndrome Population Representing 239234 Patients During 2005 to 2018 in the United States.

BackgroundPatients with acute coronary syndrome (ACS) are recognized by guidelines as remaining at high risk for adverse outcomes. Evidence from contemporary, representative ACS populations in a clinical practice setting is necessary to identify subgroups and strategies for improving patient outcomes. We aimed to describe event rates and risk factors in an ACS population over prolonged follow‐up for cardiovascular end points.Methods and ResultsWe identified 239 234 patients in the Optum Research Database (57.2% men; mean [standard deviation] age, 69.2 [12.2] years) with evidence of an ACS hospitalization (index ACS) during January 1, 2005 through December 30, 2018. Subgroups were based on index ACS event (myocardial infarction/unstable angina and revascularization status) and the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention. The 5‐year event rate for the primary end point representing nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death was 33.4% (95% CI, 33.1%–33.7%; P<0.001). The risk of experiencing the primary end point was ≈6‐fold higher immediately after discharge (≈40.9% annualized risk) as compared with the period 1+ years after hospitalization (≈6.4% annualized risk). Among subgroups, the 5‐year primary end point event rate was highest for myocardial infarction without revascularization and a Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention ≥4, at 47.9% (95% CI, 47.3%–48.4%; P<0.001) and 56.7% (95% CI, 55.9%–57.4%; P<0.001), respectively.ConclusionsPatients with ACS remain at very high risk of experiencing recurrent cardiovascular events, particularly early after discharge, with identifiable subgroups at multifold higher risk of specific clinical end points.

Association of Contemporary Statin Pretreatment Intensity and LDL-C Levels on the Incidence of STEMI Presentation

Constituting hypolipidemic and pleiotropic effects, statins stabilize coronary artery plaque and may prevent STEMI events. This study investigated the association between contemporary statin pretreatment intensity, low-density lipoprotein cholesterol (LDL-C) levels, and the type of acute coronary syndrome (ACS) presentation: STEMI vs. NSTE-ACS. Data were drawn from the ACS Israeli Survey (ACSIS), a biennial prospective national survey that took place in 2008–2018. The rate of STEMI vs. NSTE-ACS was calculated by statin use, including statin intensity (high-intensity statin therapy (HIST) and low-intensity statin therapy (LIST) prior to the index ACS event. Among 5103 patients, 2839 (56%) were statin-naive, 1389 (27%) used LIST and 875 (17%) used HIST. Statin pretreated patients were older and had a higher rates of co-morbidities, cardiovascular disease history and pretreatment with evidence-based medications. STEMI vs. NSTE-ACS was lower among HIST vs. LIST vs. statin-naive patients (31.0%, 37.8%, and 54.0%, respectively, p for trend < 0.001). Multivariate analysis revealed that HIST was independently associated with lower STEMI presentation (ORadj 0.70; 95% CI 0.57–0.86), while LIST (ORadj 0.92; 95% CI 0.77–1.10) and LDL-C < 70 mg/dL (ORadj 0.96; 95% CI 0.82–1.14) were not. In conclusion, among patients admitted with ACS, pretreatment with HIST was independently associated with a lower probability of STEMI presentation, while LIST and LDL-C < 70 mg/dL were not.

Prognostic Impact of Pancoronary Quantitative Flow Ratio Assessment in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes.

Quantitative flow ratio (QFR) has been introduced as a novel angiography-based modality for fast hemodynamic assessment of coronary artery lesions and validated against fractional flow reserve. This study sought to define the prognostic role of pancoronary QFR assessment in patients with acute coronary syndrome (ACS) including postinterventional culprit and nonculprit vessels. In a total of 792 patients with ACS (48.6% ST-segment-elevation ACS and 51.4% non-ST-segment-elevation ACS), QFR analyses of postinterventional culprit (n=792 vessels) and nonculprit vessels (n=1231 vessels) were post hoc performed by investigators blinded to clinical outcomes. The follow-up comprised of major adverse cardiovascular events, including all-cause mortality, nonfatal myocardial infarction, and ischemia-driven coronary revascularization within 2 years after the index ACS event. Major adverse cardiovascular events as composite end point occurred in 99 patients (12.5%). QFR with an optimal cutoff value of 0.89 for postinterventional culprit vessels and 0.85 for nonculprit vessels emerged as independent predictor of major adverse cardiovascular events after ACS (nonculprit arteries: adjusted odds ratio, 3.78 [95% CI, 2.21-6.45], P<0.001 and postpercutaneous coronary intervention culprit arteries: adjusted odds ratio, 3.60 [95% CI, 2.09-6.20], P<0.001). The present study for the first time demonstrates the prognostic implications of a pancoronary angiography-based functional lesion assessment in patients with ACS. Hence, QFR offers a novel tool to advance risk stratification and guide therapeutic management after ACS.

Impact of smoking cessation on depression after acute coronary syndrome

Abstract Background Smoking and depression are two risk factors for acute coronary syndrome (ACS) that often go hand-in-hand, as smokers are more likely to be depressed and people that are depressed are more likely to be smokers. Smoking cessation in depressed patients with ACS may worsen depressive symptoms, which could increase the risk of recurrence of cardiac events and decrease adherence to other cardiac risk-reducing lifestyle changes. Purpose We aimed to investigate the evolution of depression according to smoking cessation one-year after ACS. Furthermore, we investigated if there was a higher incidence of one-year depression among ACS smokers who quit in comparison to continuous smokers. Method Data from 1,822 patients with ACS of the Swiss multicenter SPUM-ACS cohort study were analysed over a one-year follow-up period. Participants were classified in three groups based on smoking status one-year post-ACS – continuous smokers, smokers who quit within the year post-ACS, and non-smokers. Depression status at baseline and at one-year after the index ACS event was assessed with the Center for Epidemiologic Studies Depression scale (CES-D) and antidepressant drug use. A multivariate adjusted logistic regression model was used to calculate the risk ratio (RR) between groups. Results In comparison to depressed smokers who continued to smoke one year post-ACS, depressed smokers who quit smoking had an adjusted RR of 2.02 (95% CI 1.04–3.92) of improving their depression. Among 543 non-depressed ACS smokers, new depression at one-year was found in 57/266 (21.4%) smokers who quit, and 68/277 (24.6%) continuous smokers, with an adjusted RR of 0.89 (95% CI 0.58–1.36) of incidence of new depression. Conclusion Smokers with depression at the time of ACS who quit smoking improved more frequently their depression compared to those who continued smoking. Although not statistically significant, there was a smaller incidence of new depression among smokers who quit after ACS in comparison to continuous smokers. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines.

The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes. We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria. In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

Association of left ventricular end-diastolic pressure with mortality in patients undergoing percutaneous coronary intervention for acute coronary syndromes.

This study sought to investigate the relation between left ventricular end-diastolic pressure (LVEDP) and outcomes in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). Risk stratification in ACS patients is important. Data on the role of LVEDP in the prognostication of ACS patients are scarce. A total of 1,410 patients undergoing PCI for ACS and with available data on LVEDP were divided according to LVEDP tertiles (lowest tertile: ≤13 mmHg, intermediate tertile: 14-20 mmHg, and highest tertile: >20 mmHg). The primary endpoint was all-cause mortality at a median follow-up of 246 [28-848] days. Median LVEDP was 16 (11-22) mmHg. All-cause mortality was 2.8%, 4.5%, and 15.0% in the lowest, the intermediate, and the highest LVEDP tertile groups (p < .001), respectively. Belonging to the highest LVEDP tertile was associated with an increased risk of all-cause mortality (adjusted hazard ratio [HR] = 2.66, 95% confidence interval [CI] [1.30, 5.47], p = .008). By receiver operating characteristic curve analysis, the optimal cut-off value for predicting all-cause mortality was 20 mmHg (sensitivity 68.3%, specificity 72.5%). There was no differential effect of LVEDP on mortality in patients with and without LV dysfunction (interaction p = .23) or ST-elevation myocardial infarction as index ACS event (interaction p = .86). In patients undergoing PCI for ACS, LVEDP was independently related with mortality. Hence, LVEDP should be incorporated into early risk stratification and clinical decision making of ACS patients.

Anti-inflammatory therapy in atherosclerosis.

Cardiovascular disease (CVD) is the leading cause of death. Although once considered merely as a lipid storage disease, studies indicate the role of inflammation in initiation and progression of atherosclerotic CVD, as well as the development of thrombotic complications. Despite significant advances in treatment of atherosclerosis, there still exists a residual risk for CVD-related morbidity and mortality. Even with optimal treatment, the rate of a new event after an index acute coronary syndrome event, such as myocardial ischemia or infarction, in the first three years has been reported to be as high as 20%. In the last decades, inflammation due to apoB-lipoproteins and other traditional risk factors, such as hypertension, diabetes and smoking, is accepted as a new target for CVD prevention. Up to now, several anti-inflammatory drugs have been tested for use in atherosclerosis. This review focuses on the current status of anti-inflammatory drug therapy for atherosclerotic CVD in humans.

Effect of selective BET protein inhibitor apabetalone on cardiovascular outcomes in patients with acute coronary syndrome and diabetes: Rationale, design, and baseline characteristics of the BETonMACE trial

After an acute coronary syndrome (ACS), patients with diabetes remain at high risk for additional cardiovascular events despite use of current therapies. Bromodomain and extra-terminal (BET) proteins are epigenetic modulators of inflammation, thrombogenesis, and lipoprotein metabolism implicated in atherothrombosis. The BETonMACE trial tests the hypothesis that treatment with apabetalone, a selective BET protein inhibitor, will improve cardiovascular outcomes in patients with diabetes after an ACS. DESIGN: Patients (n = 2425) with ACS in the preceding 7 to 90 days, with type 2 diabetes and low HDL cholesterol (≤40 mg/dl for men, ≤45 mg/dl for women), receiving intensive or maximum-tolerated therapy with atorvastatin or rosuvastatin, were assigned in double-blind fashion to receive apabetalone 100 mg orally twice daily or matching placebo. Baseline characteristics include female sex (25%), myocardial infarction as index ACS event (74%), coronary revascularization for index ACS (80%), treatment with dual anti-platelet therapy (87%) and renin-angiotensin system inhibitors (91%), median LDL cholesterol 65 mg per deciliter, and median HbA1c 7.3%. The primary efficacy measure is time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or stroke. Assumptions include a primary event rate of 7% per annum in the placebo group and median follow-up of 1.5 years. Patients will be followed until at least 250 primary endpoint events have occurred, providing 80% power to detect a 30% reduction in the primary endpoint with apabetalone. SUMMARY: BETonMACE will determine whether the addition of the selective BET protein inhibitor apabetalone to contemporary standard of care for ACS reduces cardiovascular morbidity and mortality in patients with type 2 diabetes. Results are expected in 2019.

Temporal Pattern of Growth Differentiation Factor-15 Protein After Acute Coronary Syndrome (From the BIOMArCS Study)

Growth differentiation factor-15 (GDF-15) has appeared as a promising biomarker with strong predictive abilities in acute coronary syndrome (ACS). However, studies are solely based on single measurements in the acute phase of an ACS event. The way GDF-15 patterns in post-ACS patients behave on the long term is largely unknown. We conducted a nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS event, high-frequency blood sampling was performed during 1-year of follow-up. GDF-15 was determined batchwise by electrochemiluminescence immunoassays in 37 cases with a recurrent event during 1-year follow-up, and in 74 event-free controls. Cases and controls had a mean ± standard deviation age of 66.9 ± 11.3 years and 81% were men. From 30 days onwards, patients showed stable levels, which were on average 333 (95% confidence interval 68 to 647) pg/mL higher in cases than controls (1704 vs 1371 pg/mL; p value 0.013). Additionally, in the post 30-day period, GDF-15 showed low within-individual variability in both cases and controls. In conclusion, post-ACS patients experiencing a recurrent event had stable and systematically higher GDF-15 levels during 30-day to 1-year follow-up than their event-free counterparts with otherwise similar clinical characteristics. Thus, postdischarge blood sampling might be used throughout the course of 1 year to improve prognostication, whereas, in view of the low within-individual variation, the number of repeated sampling moments might be limited.

Lipid profile, familial hypercholesterolemia prevalence, and 2-year cardiovascular outcome assessment in acute coronary syndrome: Real-life data of a retrospective cohort

The aim of this retrospective study based on real-life data was to evaluate the lipid profile and demographic, clinical, and laboratory features of patients with acute coronary syndrome (ACS) at a tertiary center and to examine the mortality rate. Information including endpoint data for at least 2 years following the index ACS event was retrieved from hospital records. Patients without sufficient follow-up data were called by phone. Modified Dutch Lipid Clinic Network criteria were used to identify the presence of familial hypercholesterolemia (FH). Factors affecting mortality in the 2-year follow-up period were evaluated using Cox regression analysis. A total of 985 ACS patients (215 females) between 21 and 93 years of age were included. The females were older and had a lower smoking rate than the males. In females, the history of obesity and hypertension, the diabetes rate, and the thyroid-stimulating hormone level were higher than those of the males. In 95.6% of the patients, lipid parameters were measured upon hospital admission. No significant difference in dyslipidemia frequency was observed between genders. The frequency of FH was 7.6%. The rate of lipid-lowering drug use was <20% at admission, >90% at discharge, and decreased to 50% in the follow-up period. The mortality rate was 3.8% in the in-hospital period and 8.1% during the 2 years of follow-up. The mortality rate in ACS patients was 3.8% in the in-hospital period and 8.1% in the 2-year follow-up period. The frequency of hypercholesterolemia was 89.5% and the rate of lipid-lowering drug use was insufficient. Secondary prevention after ACS was not adequately employed even at a tertiary center. The FH frequency was 7.6% and those with FH were observed to have ACS at a younger age than those without.

Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial

Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months. In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1:1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2·5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395. Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1·09 [95% CI 0·80-1·50]; p=0·5840). A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach. Janssen Research & Development and Bayer AG.

12 A Retrospective Study to Describe the Characteristics, Persistence and Adherence of Patients with Acute Coronary Syndromes (ACS) Prescribed Ticagrelor, Prasugrel or Clopidogrel in UK Primary Care

<h3>Background</h3> NICE recommends that following ACS, patients are treated with dual antiplatelet therapy consisting of aspirin and an additional oral antiplatelet (OAP) for up to 12 months. There is evidence that early discontinuation of dual antiplatelet therapy increases risk of recurrent event and death. <h3>Objectives</h3> To describe patient characteristics, persistence and adherence for patients prescribed OAP (clopidogrel, ticagrelor or prasugrel) in UK primary care following ACS. <h3>Methods</h3> Retrospective cohort study in primary care data from Clinical Practice Research Datalink. The cohort consisted of patients prescribed OAP for first time (index date) between Dec-2010 and May-2014, with ACS event (myocardial infarction (MI), unstable angina or ACS unspecified) ≤ 3 months prior to index date and ≥ 12 months follow-up from index date. Persistence (Kaplan-Meier) was defined as days from index date to end of period covered by last prescription, with 30 day permissible gap. Patients were censored at earliest date of: transfer from practice, death, practice last collection. Adherence was defined as proportion of persistent period covered by medication (Medication Possession Ratio). <h3>Results</h3> 9,722 patients were prescribed OAP; 8,589 (88.3%) clopidogrel, 752 (7.7%) prasugrel and 381 (3.9%) ticagrelor. The majority of patients were male (66.6%), this was more pronounced for ticagrelor (76.1%) and prasugrel (81.4%) compared to clopidogrel (64.8%). Compared to ticagrelor (mean age:62.5 years, SD:11.8) and prasugrel (mean age:58.9 years, SD:10.3), clopidogrel patients tended to be older (mean:68.8 years, SD:13.8). 37.7% of clopidogrel patients were ≥ 75 years vs 17.6% ticagrelor and 5.3% prasugrel. Overall, 89.7% had MI as index ACS event. Clopidogrel patients were more likely to have unstable angina as ACS event (3.7% vs 1.3% and 0.3% for ticagrelor and prasugrel). Clopidogrel patients were more likely to have co-morbidities, including cardiovascular disease other than ACS (62.7% vs 48.0% and 45.1% for ticagrelor and prasugrel), diabetes (20.9% vs 20.2 and 14.9% for ticagrelor and prasugrel) and renal disease (20.3% vs 9.5% and 7.3% for ticagrelor and prasugrel). Persistence, unadjusted for baseline characteristics, was similar for ticagrelor (mean:376.7, 95% CI:360.5–392.9, median:364) and prasugrel (mean:386.5, 95% CI:374.2–398.7, median:364). Mean persistence for clopidogrel was shorter: 339.7 days (95% CI:335.5–344.0, median:336). A quarter of clopidogrel patients discontinued therapy within 196 days of initiation compared to lower quartile of 336 days for ticagrelor and prasugrel. Adherence was high and similar across groups (≥ 96%). <h3>Conclusions</h3> Clopidogrel patients tended to be older, more likely to be female, have unstable angina as index ACS event as well as history of cardiovascular diseases and co-morbidities. Persistence was similar in ticagrelor and prasugrel patients, and shorter for clopidogrel. Adherence to all antiplatelets was high.

Risk factors associated with recurrent cardiovascular events at 1 and 3 years following acute coronary syndrome: longitudinal analysis 2006-2011

Purpose: Currently, there is a paucity of real-world long-term outcomes data identifying risk factors for recurrent cardiovascular events (CVEs) in patients with acute coronary syndrome (ACS). This study evaluated risk factors associated with recurrent CVEs at 1 and 3 years in a real-world cohort, post-ACS. Methods: Medical and pharmacy claims data were analyzed from >40 million patients' records in the HealthCore Integrated Research Database from 2006 to 2011, including 14 large US health plans. ACS events were identified using ICD-9 codes associated with hospitalization for acute myocardial infarction (MI; 410.xx) or unstable angina (411.1x), and excluded if <12 months pre-/post-index plan eligibility or <18 years old. A multivariable Poisson model was used to evaluate the risk of ≥1 recurrent CVE, defined as stroke, MI or coronary heart disease-related mortality, at 1 and 3 years following the index ACS event, with adjustment for baseline demographic characteristics,comorbidities, medication use and index ACS characteristics. Results: Of 140,903 ACS patients identified, mean follow-up was 1.9 years, mean age was 66.8 years and 58.6% were male. Prior to ACS, 46.3% had dyslipidemia, 41.9% diabetes mellitus and 8.6% renal dysfunction. During the index ACS hospitalization, 42.7% reported unstable angina at presentation, mean length of stay was 6.2 days, 40.3% had a CABG and/or PCI, and 3.6% died. During the follow-up period, 22.0% of patients had a recurrent CVE. At 1 and 3 years following index ACS, significant (P 0.5), while CABG at 3 years remained significant. Conclusions: This analysis provides contemporary data on risk factors associated with recurrent CVEs following ACS. Patients with baseline comorbidities had increased risk, while those with baseline OAD treatment and CABG at index had decreased risk of recurrent CVEs at 1 and 3 years following the index ACS. However, PCI significantly reduced risk only at 1 and not 3 years post-index ACS. Ongoing attention to modifiable risk factors and acute treatment strategies is essential in improving health outcomes associated with CVD.

Abstract 185: Health Care Resource Utilization of Acute Coronary Syndrome (ACS) in a Geographically Distributed US Population 2006-2011

Background: Cardiovascular (CV) disease is the leading cause of mortality in both men and women in the US, resulting in substantial health care utilization and costs. There are limited data quantifying long-term resource utilization following an ACS event. Objectives: Evaluate overall and CV-related health care utilization following an ACS event in patients with/without recurrent CV events (CVEs) post-discharge. Methods: Patients with ≥1 ICD-9 CM code for acute myocardial infarction MI) (410.xx) or unstable angina (411.1x) during ACS hospitalization were identified from the HealthCore Integrated Research Database 01/01/2006-09/30/2011. Index date was defined as the first ACS event. Patients with &lt;12 months’ pre-/post-index plan eligibility or age &lt;18 years were excluded. Recurrent CVEs were defined as any occurrence of MI, non-fatal stroke or coronary heart disease-related mortality after the index ACS event. Overall and CV-related health care resource utilization following the index ACS event were evaluated in patients with/without recurrent CVEs. Results: Of 140,903 patients, 22.0% had ≥1 subsequent CVE during follow-up. Patients with/without recurrent CVEs were older (mean 72.4 vs. 65.2 years) and had more comorbidities (mean baseline Deyo-Charlson Index scores 2.4 vs. 1.6). Mean (median) follow up was 2.0 (1.6) and 1.9 (1.5) years in patients with/without recurrent CVEs, respectively. Mean (median) number of 1-year post-index overall and CV-related hospitalizations in the recurrent CVE cohort was higher than the non-recurrent cohort (2.81 [1.98] and 2.40 [1.54] vs. 1.56 [1.23] and 1.30 [0.82], respectively). Mean number of 1-year post-index overall outpatient and office visits were higher in the recurrent versus non-recurrent cohort (31.82 [36.63] and 14.72 [11.15] vs. 21.65 [25.68] and 11.89 [9.67]). Mean annual 3-year utilization post-index showed the same trend (Table). Conclusion: Patients with recurrent CVEs had higher 1- and 3-year post-index overall and CV-related utilization as compared with patients without recurrent CVEs. More aggressive strategies to manage this increased long-term utilization is warranted. This study underscores the need to prevent subsequent adverse CVEs, ultimately to improve patient outcomes and help reduce overall health care utilization.

Does the Potential Overuse of Routine Post PCI Stress Testing and Revascularization Inspire Courage to Embrace More Evidence-Based Decision Making?

Among patients with coronary artery disease (CAD), there are widely divergent clinical practice styles in the use of myocardial revascularization, medical therapy, and the assessment of symptomatic or functional status after the initiation of treatment. Frequently, patients who have undergone initial successful revascularization, principally with percutaneous coronary intervention (PCI), are re-evaluated with diagnostic testing (both noninvasive and invasive) within the first year of follow-up, presumably to document objectively the absence of recurrent ischemia, despite the fact that current clinical practice guidelines proscribe such routine testing in otherwise asymptomatic individuals. Clearly, all clinicians seek to achieve optimal care for their patients, but both external pressures from payers and the need to conform to established treatment guidelines often create conflict and uncertainty in physician decision-making regarding what is right. Article see p 11 There should be general agreement that the best outcomes in patients with CAD are observed when comprehensive risk factor modification, intensive medical therapy, and appropriate use of revascularization are used in the setting of judicious clinical decision-making that is evidence based. Optimal medical therapy can be defined as that which uses guideline-directed, disease-modifying interventions (eg, aspirin with or without thienopyridines, statins, and inhibitors of the renin-angiotensin system) as well as therapeutic agents directed toward angina relief and control of ischemia (eg, β-blockers, calcium channel blockers, nitrates, or ranolazine—used alone or in combination).1 For patients with CAD who are symptomatic, antianginal therapy is not considered to be optimal unless at least 2 antianginal agents have been prescribed, and, generally, a desired, favorable treatment effect is achieved in sufficient doses. Similarly, stress testing in the patient with CAD may be performed for evaluation of ischemic symptoms, to assess prognostic risk or, when there is concern that a revascularization procedure has been incomplete, to assess the functional significance of residual obstructive …

Directionality of the relationship between depressive symptom dimensions and C-reactive protein in patients with acute coronary syndromes.

Previous theoretical models predict that elevated inflammation may predict later depressive symptoms, but bidirectional associations are possible. We examined whether depressive symptoms or inflammation predicts change in the other for a 3-month period in a sample of adults with acute coronary syndromes (ACS). During hospitalization for their index ACS event (baseline) and then again 1 and 3 months later, 163 post-ACS patients completed the Beck Depression Inventory, a measure of depressive symptom severity with cognitive-affective and somatic-affective subscales. C-reactive protein (CRP) was also assessed at each visit; known correlates of depression and CRP were assessed at baseline. Path analyses were conducted to evaluate prospective associations between depressive symptoms and log-transformed CRP values and whether strength and/or directionality varied by specific depressive symptom dimensions. Baseline total depressive symptom severity predicted a smaller decrease in CRP from baseline to 1 month (unstandardized parameter estimates [B] = 0.04, p < .001) controlling for all covariates, as did baseline cognitive-affective depressive symptom severity (B = 0.10, p = .02). Baseline somatic-affective depressive symptom severity did not predict change in CRP (B = -0.002, p = .94). CRP did not predict 1- or 3-month change in total, cognitive-affective, or somatic-affective depressive symptom severity. The results did not differ for men and women. Greater cognitive-affective and total depressive symptom severity at the time of a cardiac event predicts a smaller decrease in CRP 1 month later, but there was no evidence in this study that CRP predicts change in depressive symptoms.