Prior Heart Attack Research Articles

Advanced Coherent System For Predicting Cardiac Risks using Data Mining Techniques

Considering health care and medical industry related data there are millions or tons of data which contains numerous hidden information. This information can be mined through which we can make effective decisions in their related industry. There are numerous far advanced methods and techniques in mining and determining the useful decisions using the retrieved useful information. Such an effective system called Coherent cardiac risk prediction system (CCRPS) is developed using neural networks in early detection or prediction of various risk level in cardiac disease. This work employs a multilayer perception neural network with back propagation as the training algorithm. This system aims in predicting the likelihood of patients getting disease related to cardiac such as CHD, a prior heart attack, uncontrolled hypertension, abnormal heart valves, congenital heart disease (heart defects present at birth) and heart muscle disease. The system uses a total of twenty-one medical related parameters such as age, sex, chest pain type, resting blood pressure (in mm Hg on admission to the hospital), serum cholesterol in mg/dl, Smoking, stress etc for prediction purpose. It enables or activated the important knowledge such as how the medical factors related to cardiac disease and patterns and the relationship to be established. Through this system we obtain effective results that have crafted its own diagnostic method or way to predict the risk level measurement of cardiac disease.

PMU7 ASSOCIATION OF ADVERSE CHILDHOOD EVENTS AND HEALTH OUTCOMES WITHIN THE BRFSS DATABASE IN PENNSYLVANIA

Numerous studies have established the relationship between negative health outcomes and adverse childhood events (ACEs); however, the unique contribution of the ACEs vs. health behaviors on outcomes is difficult to distinguish. The purpose of this study is to assess the relationship between ACEs and chronic disease outcomes (CDs) while removing the influence of smoking. We conducted a cross-sectional study of adults in Pennsylvania using the 2014 Center for Disease Control’s Behavioral Risk Factor Surveillance System (BRFFS) survey. Self-reported ACEs were summed from eight survey questions to calculate the primary independent variable: ACE score. CDs included prior heart attack, current asthma, and self-reported health status. The association between ACEs and CDs, ACEs and smoking status, and ACEs and CDs adjusting for smoking were computed using multiple logistic regression. All models were covariate-adjusted. The analysis included a total of 9,241 adult respondents of whom 51% had at least one ACE and 6% had ≥ five ACEs. ACEs were significantly related to smoking. After adjusting for covariates only, individuals with ≥ five ACEs had statistically significantly increased odds of experiencing CDs [ORs of 2.06, 2.33, and 3.30, for heart disease, asthma, and poor self-rated health, respectively]. When adjusting for smoking status, there was evidence of mediation between ACEs and the CD outcomes by smoking [ORs of 1.79, 2.34, and 2.73 for heart disease, asthma, and poor self-rated health, respectively], but the relationships remained statistically significant. Individuals experiencing ≥ five ACEs were at higher odds of being diagnosed with CDs, even after controlling for smoking. Thus, we conclude that smoking mediated the relationship between ACEs and the CD outcomes. Future research should be conducted to further unpack the relationship between multiple health behaviors, ACEs and CDs.

Heart Attack and Stroke Symptoms Knowledge of Native Hawaiians and Pacific Islanders in the United States: Findings From the National Health Interview Survey.

Native Hawaiians and other Pacific Islanders (NHPI) suffer disproportionate rates of death from heart attack and stroke; however, little is known about NHPI heart attack and stroke symptoms knowledge. We used multivariable logistic regression to examine associations between heart attack and stroke symptoms knowledge and electronic health (eHealth) use, education, engaging in health risk behaviors, and having an at-risk diagnosis or a past heart attack and/or stroke. The analytic sample included 2,172 NHPI adults responding to the 2014 NHPI-National Health Interview Survey. NHPI reported moderate to high levels of heart attack and stroke symptoms knowledge. NHPI with an at-risk diagnosis were significantly more likely to know three of five heart attack symptoms. Engaging in health risk behaviors increased the odds of knowing one heart attack symptom. Neither a prior heart attack nor a prior stroke increased the likelihood of recognizing most symptoms of heart attack or stroke. eHealth use was associated with increased likelihood for knowing heart attack and stroke symptoms. The findings of this study can be used to inform interventions that support the Healthy People 2020 goals to increase the proportion of adults who are aware of the symptoms of heart attack and stroke and to reduce heart attack and stroke disparities.

Reduction in Subtypes and Sizes of Myocardial Infarction With Ticagrelor in PEGASUS-TIMI 54.

BackgroundTicagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance.Methods and ResultsMIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow‐up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention–related (Type 4a) and coronary artery bypass graft–related (Type 5) each accounted for <1%. Half of MIs (520, 50%) had a peak troponin ≥10x upper limit of normal and 21% of MIs (220) had a peak troponin ≥100× upper limit of normal. A total of 21% (224) were ST‐segment–elevation MI STEMI. Overall ticagrelor reduced MI (4.47% versus 5.25%, hazard ratio 0.83, 95% confidence interval 0.72–0.95, P=0.0055). The benefit was consistent among the subtypes, including a 31% reduction in MIs with a peak troponin ≥100× upper limit of normal (hazard ratio 0.69, 95% confidence interval 0.53–0.92, P=0.0096) and a 40% reduction in ST‐segment elevation MI (hazard ratio 0.60, 95% confidence interval 0.46–0.78, P=0.0002).ConclusionsIn stable outpatients with prior MI, the majority of recurrent MIs are spontaneous and associated with a high biomarker elevation. Ticagrelor reduces the MI consistently among subtypes and sizes including large MIs and ST‐segment elevation MI.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562.

Return of Oral Anticoagulation in Chronic Stable Coronary Disease.

Antithrombotic therapy has been a cornerstone of secondary prevention for coronary artery disease (CAD) for the last 65 years. The first randomized trial with warfarin was carried out in New York and published in 1949. This landmark study was followed by many studies underscoring the benefit of warfarin. In the 1980s, aspirin emerged as a simple, lifesaving, and very cheap alternative and stayed there until today. In chronic CAD, the question emerged as to whether anticoagulant or antiplatelet agents are the better therapeutic. Several head-to-head comparisons of warfarin alone versus aspirin alone showed a large benefit of warfarin in reduction of myocardial infarction (MI) and stroke.1 Because of the complexity and bleeding risks with warfarin, few doctors returned to it, especially after the CURE trial (Clopidogrel in Unstable Angina to Prevent Recurrent Events) with aspirin plus clopidogrel was published. Thus, dual antiplatelet therapy (DAPT) became the standard of care after MI. Better results with DAPT after acute coronary syndromes (ACS) were obtained when clopidogrel was replaced with the stronger P2Y12 blockers prasugrel and ticagrelor. Another option was to prolong DAPT after MI beyond the guideline-mandated 12 months, when P2Y12 blockade traditionally is discontinued. Compared with aspirin monotherapy, DAPT prolongation is effective against ischemic events in several recent large randomized trials (DAPT2 and PEGASUS TIMI-54 [Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54]3) but is associated with increased bleeding without a significant mortality …

Management of Acute Coronary Syndromes

Management of Acute Coronary Syndromes

Ticagrelor for Secondary Prevention of Atherothrombotic Events in Patients With Multivessel Coronary Disease

BackgroundPatients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events. ObjectivesThe authors investigated the efficacy and safety of ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial. MethodsPatients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months. ResultsA total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HRadj]: 1.24; p = 0.026) and for coronary events (7.67% vs. 5.34%, HRadj: 1.49; p = 0.0005). In patients with MVD, ticagrelor reduced the risk of MACE (7.94% vs. 9.37%, HR: 0.82; p = 0.004) and coronary events (6.02% vs. 7.67%, HR: 0.76; p < 0.0001), including a 36% reduction in coronary death (HR: 0.64; 95% confidence interval: 0.48 to 0.85; p = 0.002). In this subgroup, ticagrelor increased the risk of TIMI major bleeding (2.52% vs. 1.08%, HR: 2.67; p < 0.0001), but not ICH or fatal bleeds. ConclusionsPatients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

Frequency, Predictors, and Impact of Combined Antiplatelet Therapy on Venous Thromboembolism in Patients With Symptomatic Atherosclerosis.

Observational studies suggest that symptomatic atherosclerosis may be associated with risk of venous thromboembolism (VTE). Prior randomized studies have demonstrated a significant reduction in recurrent VTE with aspirin monotherapy. Whether VTE risk is associated with more severe symptomatic atherosclerosis and more intensive antiplatelet therapy reduces VTE risk beyond aspirin monotherapy is unknown. TRA2P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction) (vorapaxar) and PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) (ticagrelor) were blinded, randomized placebo-controlled trials of antiplatelet therapy for the prevention of ischemic events in stable patients with symptomatic atherosclerosis. Two blinded vascular specialists systematically identified symptomatic venous thromboembolic events in both trials. Of 47 611 patients with stable vascular disease followed for 3 years in both studies there were 343 VTE events in 301 patients (Kaplan-Meier rate at 3 years, 0.9% for placebo). The risk of VTE was independently associated with age, body mass index, polyvascular disease, chronic obstructive pulmonary disease, and malignancy. The burden of atherosclerosis manifested as an increasing number of symptomatic vascular territories was associated with a graded increase in the 3-year rates of VTE (0.76% for 1, 1.53% for 2, and 2.45% for 3 territories). More intensive antiplatelet therapy (vorapaxar and ticagrelor pooled) significantly reduced the risk of VTE by 29% compared with background antiplatelet therapy, from 0.93% to 0.64% at 3 years (hazard ratio, 0.71; 95% confidence interval, 0.56-0.89; P=0.003). The rate of VTE in patients with atherosclerosis is ≈0.3% per year while on treatment with ≥1 antiplatelet agent, with increased risk independently associated with the number of symptomatic vascular territories. More intensive antiplatelet therapy reduces the risk of VTE. These data suggest a relationship between atherosclerosis burden and VTE risk, and they support inclusion of VTE as a prospective end point in long-term secondary prevention trials evaluating the risks and benefits of antiplatelet therapies in patients with atherosclerosis. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562.

Cardiovascular Immunotherapy and the Role of Imaging.

Despite significant advances in prevention and treatment, cardiovascular diseases (CVDs) remain the most common cause of death in the United States.1–3 In part, and compared with treatment developments in oncology, this is because of the lack of current generation CVD precision therapies.4–6 Most CVDs are caused by atherosclerosis, a disease process that causes thickening of the arterial wall because of inflammation and lipid accumulation, resulting in plaque formation.7,8 Macrophage dynamics plays a central role in atherosclerosis progression, vessel wall destabilization, and—as has been recently discovered—plaque aggravation because of myocardial infarction.9–11 Therefore, and despite current standardized treatments, ≈25% of patients who had myocardial infarction or stroke will experience secondary major adverse cardiovascular events, often more harmful than the primary event.12–14 To break this vicious cycle, innovative and tailored therapeutic strategies are needed. Various targeted immunotherapies that showed anticancer potential in in vitro screens also displayed in vivo potential in mouse models. Such proof-of-concept studies in validated syngeneic mouse tumor models not only provide information on in vivo efficacy but also disclose the targeted immunotherapies’ underlying mechanism of action and safety profile. However, immunotherapies’ high costs and the identification of amendable patients compromise clinical translation.15,16 Continued and focused efforts are needed to understand patient responsiveness and reduce high dropout rates in trials. A parallel effort focused on the development of novel imaging tools that can guide patient selection may offer a potential solution. Positron emission tomography (PET) can be used to trace immunotherapies. So-called immunoPET uses antibodies, developed for cancer treatment, that selectively recognize a specific epitope on target cells. The antibodies are labeled with radioactive isotopes, such as zirconium-89 or iodine-124, with relatively long decay half-lives of 3.27 and 4.18 days, respectively, to …

TCT-584 A randomized, pharmacodynamic comparison of low dose ticagrelor to clopidogrel in patients with prior myocardial infarction: The ALTIC study

In patients with prior myocardial infarction (MI) long-term treatment with clopidogrel reduced ischemic events, with an increase in bleeding. In the Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin -Thrombolysis in Myocardial Infarction 54 (PEGASUS-

Efficacy and Safety of Ticagrelor Over Time in Patients With Prior MI in PEGASUS-TIMI 54

BackgroundTicagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time. ObjectivesThe study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization. MethodsThe PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3). ResultsA total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65). ConclusionsPatients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

Cost-Effectiveness of Long-Term Ticagrelor in Patients With Prior Myocardial Infarction: Results From the PEGASUS-TIMI 54 Trial

BackgroundIn patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding. ObjectivesThe authors evaluated cost-effectiveness of ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years. MethodsThe authors performed a prospective economic substudy alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162 patients to ASA alone, ticagrelor 60 mg twice daily + low-dose ASA, or ticagrelor 90 mg twice daily + low-dose ASA. Medical resource use data were collected over a median 33-month follow-up. Costs were assessed from the U.S. health care system perspective. In-trial data relating to survival, utility, and costs were combined with lifetime projections to evaluate lifetime cost-effectiveness of the Food and Drug Administration–approved lower-dose ticagrelor regimen (60 mg twice daily). ResultsHospitalization costs were similar for ticagrelor 60 mg and placebo ($2,262 vs. $2,333; 95% confidence interval for difference −$303 to $163; p = 0.54); after inclusion of a daily ticagrelor 60 mg cost of $10.52, total costs were higher for ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p < 0.001). In-trial quality-adjusted life-years (QALYs) were similar (2.28 vs. 2.27; p = 0.34). Over a lifetime horizon, ticagrelor was associated with QALY gains of 0.078 and incremental costs of $7,435, yielding an incremental cost-effectiveness ratio (ICER) of $94,917/QALY gained. Several high-risk groups had more favorable ICERs, including patients with >1 prior MI, multivessel disease, diabetes, renal dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age <75 years (ICER = $44,779/QALY gained), and patients with peripheral artery disease (ICER = $13,427/QALY gained). ConclusionsFor patients with a history of MI >1 year previously, long-term treatment with ticagrelor 60 mg + low-dose ASA yields a cost-effectiveness ratio suggesting intermediate value based on current guidelines. Ticagrelor appears to provide higher value for patients in several recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

Implications of the PEGASUS-TIMI 54 trial for US clinical practice

ObjectivesThis study aims to determine the proportion of real-world patients with myocardial infarction (MI) who would have been eligible for the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with...

Prevention of Stroke With Ticagrelor in Patients With Prior Myocardial Infarction: Insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction)

BACKGROUND: In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population. METHODS: Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis. RESULTS: Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001). CONCLUSIONS: High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke.

Prevention of Stroke with Ticagrelor in Patients with Prior Myocardial Infarction: Insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54).

In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population. Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis. Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001). High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562.

Reduction in Ischemic Events With Ticagrelor in Diabetic Patients With Prior Myocardial Infarction in PEGASUS–TIMI 54

BackgroundPatients with diabetes appear to be at elevated risk of atherothrombotic events. ObjectivesThe purpose of this study was to determine the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events in patients with diabetes and prior myocardial infarction (MI). MethodsWe examined the subgroups of patients with diabetes (n = 6,806) and without diabetes (n = 14,355) from PEGASUS–TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54), in which 21,162 patients with a history of MI 1 to 3 years prior and with additional risk factors were randomized to ticagrelor (90 or 60 mg twice daily) or placebo. Patients were followed for a median of 33 months. The primary efficacy endpoint was major adverse cardiovascular events (MACE) (cardiovascular death, MI, stroke) and the primary safety endpoint was TIMI (Thrombolysis In Myocardial Infarction) major bleeding. ResultsThe relative risk reduction in MACE with ticagrelor was consistent for the pooled doses versus placebo in patients with diabetes (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.72 to 0.99; p = 0.035) and without diabetes (HR: 0.84; 95% CI: 0.74 to 0.96; p = 0.013; p interaction = 0.99). As patients with diabetes were at higher risk of MACE, the absolute risk reduction tended to be greater in patients with versus without diabetes (1.5% vs. 1.1%, with corresponding 3-year number needed to treat of 67 vs. 91). In patients with diabetes requiring pharmacological therapy (n = 5,960), the absolute risk reduction was 1.9% with a 3-year number needed to treat of 53. Additionally, in patients with diabetes, ticagrelor reduced cardiovascular death by 22% and coronary heart disease death by 34%. Similar to patients without diabetes, there was increased TIMI major bleeding in patients with diabetes (HR: 2.56; 95% CI: 1.52 to 4.33; p = 0.0004). ConclusionsIn patients with diabetes with prior MI, adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events, including cardiovascular and coronary heart disease death. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease

BackgroundPeripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). ObjectivesThis study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI. MethodsPEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up. ResultsA total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026). ConclusionsAmong stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562)

Platelet Inhibition With Ticagrelor 60 mg Versus 90 mg Twice Daily in the PEGASUS-TIMI 54 Trial

BackgroundThe PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial studied 2 doses of ticagrelor, 90 mg twice a day (bid) and 60 mg bid, for long-term prevention of ischemic events in patients with prior myocardial infarction. Both doses similarly reduced the rate of ischemic events versus placebo. The pharmacokinetics and pharmacodynamics of ticagrelor 60 mg bid have not been studied. ObjectivesIn this study, the authors sought to study the pharmacokinetics and pharmacodynamics for ticagrelor 60 mg compared with 90 mg bid. MethodsA total of 180 patients who received >4 weeks of study medication had blood sampling in the morning pre-maintenance dose and again 2 h post-dose. All patients received aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were determined. P2Y12 inhibition was assessed by the VerifyNow P2Y12 assay (Accumetrics, Inc., San Diego, California) (P2Y12 reaction units [PRU]), light transmittance aggregometry (adenosine diphosphate 5 and 20 μmol/l and arachidonic acid), and vasodilator-stimulated phosphoprotein phosphorylation assays. VerifyNow Aspirin assays and serum thromboxane B2 measurements were performed. ResultsMean pre- and post-dose plasma levels of ticagrelor were 35% and 38% lower, respectively, with 60 mg versus 90 mg. Both doses achieved high levels of platelet inhibition pre- and post-dose, with numerically slightly more variability with 60 mg: mean (SD) pre-dose PRU values were 59 ± 63 and 47 ± 43 for ticagrelor 60 and 90 mg, respectively (p = 0.34). High platelet reactivity, determined as PRU >208, was rare with the 60-mg pre-dose and was absent post-dose. Platelet reactivity pre- and post-dose, as measured by light transmittance aggregometry or vasodilator-stimulated phosphoprotein assays, was numerically but not significantly lower with 90 mg than with 60 mg. Aspirin response was not affected by either dose. ConclusionsTicagrelor 60 mg bid achieved high levels of peak and trough platelet inhibition in nearly all patients, similar to that with 90 mg bid, helping to explain the efficacy of the lower ticagrelor dose in PEGASUS-TIMI 54.

Long-term use of ticagrelor in patients with prior heart attack: ticagrelor plus aspirin versus aspirin monotherapy

ABSTRACTReview of: Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-1800.This Practice Pearl reviews the recent study Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared With Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54). It challenges the current standard of care of 12 months of dual antiplatelet followed by aspirin indefinitely. The study demonstrated that patients who received ticagrelor, either the 60 mg or 90 mg twice daily plus aspirin, showed a decreased risk of cardiovascular death, myocardial infarction, or stroke. The PEGASUS-TIMI 54 trial also proved that the benefit of ticagrelor was seen early and continued to accrue over time, with a median of 33 months of follow-up, meaning that the benefit persists over time. It is important to note that both doses of the ticagrelor were associated with higher incidence of bleeding, but the rates of fatal bleeding did not show any difference between the ticagrelor or placebo.

Five-year outcomes of catheter ablation in patients with atrial fibrillation and left ventricular systolic dysfunction.

Catheter ablation of atrial fibrillation (AF) is an established therapy for symptomatic patients. The long-term efficacy and impact of catheter ablation among patients with severe systolic heart failure (SHF) requires additional study to understand if outcomes achieved at 1 year are maintained and mechanisms of AF recurrence. Three groups with SHF and 5 years of follow-up were matched 1:4:4 by age (±5 years) and sex: AF ablation patients receiving their first ablation (n = 267), AF patients that did not receive an ablation (n = 1,068), and SHF patient without AF (n = 1,068). SHF was based upon clinical diagnosis and an ejection fraction (EF) ≤35%. Patients were followed for 5-year primary outcomes of AF recurrence, heart failure, stroke, death, and cardiac function. At 5 years, 60.7% of patients had clinical recurrence of AF. Diabetes and a prior heart attack were significant predictors of long-term risk of AF recurrence. Long-term mortality rates were 27%, 55%, 50%, in the AF ablation, AF, and no AF groups, respectively (P < 0.0001), with the lower rates attributed to lower cardiovascular mortality. At 5 years, there was no difference in EF, yet HF hospitalizations were lower following AF ablation compared to patients with AF and no ablation. Stroke rates at 5 years trended to be lower in the AF ablation group, but the difference was not statistically significant. Recurrence rates of AF in patients with SHF after ablation are common at 5 years with an anticipated ongoing increase. Long-term AF-related comorbidities tended to be less in the AF ablation group.