Risk Of Recurrent Events Research Articles

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.

Cognitive dysfunction and poor health literacy are common in veterans presenting with acute coronary syndrome: insights from the MEDICATION study.

BackgroundPatient nonadherence to cardiac medications following acute coronary syndrome (ACS) is associated with increased risk of recurrent events. However, the prevalence of cognitive dysfunction and poor health literacy among ACS patients and their association with medication nonadherence are poorly understood.MethodsWe assessed rates of cognitive dysfunction and poor health literacy among participants of a clinical trial that tested the effectiveness of an intervention to improve medication adherence in patients hospitalized with ACS. Of 254 patients, 249 completed the Rapid Estimate of Adult Literacy in Medicine, Revised (REALM-R) survey, an assessment of risk for poor literacy, and the St Louis University Mental Status (SLUMS) exam, a tool assessing for neurocognitive deficits, during ACS hospitalization. We assessed if SLUMS or REALM-R scores were associated with medication adherence.ResultsBased on SLUMS score, 14% of patients were categorized as having dementia, and 52% with mild neurocognitive disorder (MNCD). Based on REALM-R score of ≤6, 34% of patients were categorized as at risk for poor health literacy. There was no association between poor health literacy and medication nonadherence. Of those with MNCD, 35.5% were nonadherent, compared to 17.5% with normal cognitive function and 6.7% with dementia. In multivariable analysis, cognitive dysfunction was associated with medication nonadherence (P=0.007), mainly due to an association between MNCD and nonadherence (odds ratio =12.2, 95% confidence interval =1.9 to 243; P=0.007). Cognitive status was not associated with adherence in patients randomized to the intervention.ConclusionCognitive dysfunction and risk for poor health literacy are common in patients hospitalized with ACS. We found an association between MNCD and medication nonadherence in the usual care group but not in the intervention group. These findings suggest efforts to screen for MNCD are needed during ACS hospitalization to identify patients at risk for nonadherence and who may benefit from an adherence intervention.

Glycemic control and acute coronary syndrome: the debate continues

Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality in worldwide population.1 Patients admitted to Emergency Care Unit and/or Intensive Coronary Care Unit remain at high risk of recurrent events, hospitalization, and cardiovascular death.1 In last decades, diabetic mellitus (DM) affected patients have been diagnosed as one of four patients with AMI.2 New randomized controlled trials have investigated pharmacologic and non-pharmacologic management strategies to reduce all-cause mortality for patients with diabetes and AMI. In fact, the International American and European guidelines1,2 have reported evidence-based recommendations for treating AMI and DM. Parallel to an innovative and broader use of anti-ischaemic and anti-remodelling drugs to treat AMI, the primary angioplasty [primary percoutaneous coronary intervention (pPCI)] therapeutical development has drastically reduced the mortality in affected patients.1 The not discussable percutaneous coronary intervention (PCI) impact in AMI patients prognosis is not so great as expected in DM patients.3 Moreover, we have to consider DM patients, as a population of patients with different clinical characteristics, that render more difficult the best clinical pharmacological and non-pharmacological treatment (pPCI) to reduce worse prognosis during AMI. For these reasons, we have to improve current clinical diagnosis and treatment, and planning future strategies for DM affected by AMI. In the current study,4 Singh and co-workers evidenced that ‘despite rapid revascularization and treatment of hyperglycaemia, patients with acute hyperglycaemia (AH) continue to have …

Community-based comprehensive lifestyle programs in patients with coronary artery disease: Objectives, design and expected results of Randomized Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists 2 trial (RESPONSE 2)

Patients with coronary artery disease (CAD) are at high risk of recurrent events. A healthy lifestyle can significantly reduce this risk. A previous trial, Randomized Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists (RESPONSE), demonstrated that nurse-coordinated outpatient clinics improve drug treatment of cardiovascular risk factors. However, lifestyle-related risk factors, including smoking, overweight, and physical inactivity, were common and remained largely unchanged at follow-up in most patients (66%). The aim of the current study is to evaluate the impact of 3 community-based lifestyle programs in patients after hospitalization for CAD. We are conducting a multicenter (n = 15), randomized trial that will recruit 800 patients to test the efficacy of up to 3 widely available commercial lifestyle programs, aimed at patients and their partners, on top of usual care. These programs are aimed at smoking cessation (Luchtsignaal(®)), weight loss (Weight Watchers(®)), and improving physical activity (Philips DirectLife(®)). The primary outcome at 12months is the proportion of patients in whom at least 1 lifestyle risk factor is improved without deterioration in any of the other 2, and a relative increase of at least 30% in this proportion is considered clinically relevant.

Recurrent stroke in patients with patent foramen ovale: An observational prospective study of percutaneous closure of PFO versus non-closure

AimsObservational studies favor percutaneous closure of patent foramen ovale (PFO) over medical therapy to reduce the risk of recurrent stroke, whereas randomized clinical trials have not shown significant differences. This study aims to compare long-term outcomes of PFO closure versus non-closure. Methods and resultsPatients with PFO and stroke considered for PFO closure were invited to a long-term clinical follow-up. Of the 314 patients, 151 (48%) were accepted for closure and 163 (52%) were not accepted (mean age 50 vs. 58years). The cumulative incidence of all-cause mortality, stroke or transient ischemic attacks (TIAs) for closure vs. non-closure under a mean follow-up time of five years was 10.6% (16 events) vs. 12.9% (21 events), p=0.53. Six patients, 3.7% vs. 3.6%, died in each group, but no deaths were associated with PFO closure, recurrent stroke or TIA. The incidence of recurrent stroke or TIA for closure vs. non-closure was 6.6% (10 events) vs. 9.2% (15 events), p=0.63. The respective event rates for stroke were 3.9% (6 events) vs. 5.5% (9 events), p=0.50 and for TIA, 2.6% (4 events) vs. 3.7% (6 events), p=0.59. ConclusionPFO closure was associated with a low risk of recurrent events; however, compared to the non-closure group, no significant differences could be demonstrated. Careful patient selection can avoid under- as well as over-treatment of PFO patients.

The Association Between Central Fat Distribution and Recurrent Cardiovascular Disease Events in Female Survivors of Nonfatal Myocardial Infarction

Visceral fat has been shown to be an important predictor of metabolic alterations that lead to increased cardiovascular disease (CVD) risk factors, morbidity, and mortality. The aim of this study was to investigate the association between central fat distribution and the risk of recurrent coronary events among a cohort of female myocardial infarction (MI) survivors. Participants included 356 women (mean ± SD age, 55 ± 8.71 years) discharged alive after an incident MI from hospitals in Erie and Niagara (New York) counties between 1996 and 2004. A recurrent cardiovascular event was any nonfatal or fatal International Classification of Diseases, Ninth Revision-coded diagnosis between 390 and 450. The mean ± SD follow-up time was 4.01 ± 2.6 years. Interviews and self-administered follow-up surveys were used to collect pertinent information, and a search of the National Death Index Plus database was completed. Eighty-five women experienced a recurrent cardiovascular event. Using Cox proportional hazards analyses, the crude model for body mass index suggested that after incident MI, women had a 39% risk of a recurrent CVD event (hazard ratio [HR], 1.39; confidence interval [CI], 0.76-2.54; P = .293), whereas crude models for waist circumference and sagittal abdominal distention showed the risk to be more than twice as high (HR, 2.12; CI, 1.08-4.16; P = .010; and HR, 2.16; CI, 1.09-4.28; P = .037, respectively). Both measures of central fat distribution appeared to be better predictors of recurrent cardiovascular events when compared with body mass index, whereas sagittal abdominal distention was the better predictor compared with waist circumference, even after multivariate adjustment. After adjusting for secondary prevention interventions-statin, aspirin, β-blocker use, and physical activity-the risk of recurrent event was observed to decrease by about 1%. These results suggest that central fat distribution is positively associated with a recurrence of cardiovascular events after incident MI in women. The absence of decreased risk with secondary prevention interventions suggests that more investigation into the association of central abdominal fat and secondary prevention management is warranted.

EVALUATION OF RESIDUAL PLATELET REACTIVITY AFTER ST ELEVATION MYOCARDIAL INFARCTION IN HUMAN IMMUNODEFICIENCY VIRUS, THE EVRE2ST-HIV STUDY

High on-treatment platelet reactivity is an independent risk factor of major adverse cardiovascular events following percutaneous coronary intervention or Acute Coronary Syndrome (ACS). HIV-infected patients have a higher risk of recurrent events after ACS than HIV uninfected patients. We

Imaging Myocardium at Risk and Coronary Inflammation in Non–ST-Segment Elevation Myocardial Infarction

Patients with non-ST-segment elevation myocardial infarction (NSTEMI) represent a heterogeneous group in terms of jeopardized myocardium, pathogenetic mechanisms, and risk of recurrent events. In particular, estimation of myocardium at risk may be challenging before angiography. Yet the mechanisms leading to coronary instability underlying acute coronary syndromes (ACS) have not been completely elucidated. In this report (figure), we describe the potential utility of FDG PET in defining the myocardium at risk and to unravel coronary inflammation in one NSTEMI patient with normal level of C-reactive protein. Optical coherence tomography (OCT) images of culprit lesions are also shown.

Abstract 17806: The Prognostic Importance of Frequent Premature Atrial Contractions Following Ischemic Cerebrovascular Events

Background: Following ischemic cerebrovascular accident (CVA) or transient ischemic attack (TIA) aggressive risk factor modification is undertaken to reduce the risk of recurrent events. Holter monitoring is advocated to facilitate the detection and treatment of Atrial Fibrillation (AF). Frequent Premature Atrial Contractions (PACs) are associated with the development of AF, but to date it is unknown whether the burden of PACs on Holters is of any prognostic importance following CVA/TIA. Objective: PACs on Holter monitoring may be a marker for recurrent cerebrovascular events post CVA/TIA. Methods: Retrospective analysis was performed on Holters of patients with CVA/TIA enrolled in a prior population based stroke study. Frequent PACs were defined as a rate of PACs ≥ 100 per 24 hours. The primary endpoint was recurrent CVA or TIA. Results: 84 cases (61.0% male) were reviewed. Mean age was 69.7 ± 12.4 years. Mean time to follow-up was 2514.6 ± 91.2 days. The average number of PACs in the frequent group (Hi-PAC, 21 patients) was 1610.8 ± 4541.4 compared with 21.8 ± 27.6 in those with less than 100 PACs (Lo-PAC, 63 patients). There was no statistically significant difference in age, gender, hypertension or diabetes between the two groups. On follow-up there were 20 recurrent events and 33 patients died. In the Hi-PAC group there were 8 (38.1%) recurrent events, and 16 (76.2%) patients died versus 12 (18.8%) and 17 (26.6%) respectively in Lo-PAC group. On Cox regression analysis the Hazard ratio (HR) for recurrent events was 2.75 (95% confidence interval (CI) 1.08 to 7.01). Kaplan Meier curves revealed a statistically significant difference in recurrance rates between the two groups (p &lt; 0.05). There was also a statistically significant difference in overall mortality on Kaplan Meier survival analysis (p &lt; 0.001), and with a hazard ratio on Cox regression analysis of 3.47 (95% CI 1.74 [[Unable to Display Character: &amp;#8211;]] 6.91). There was no significant difference in incidence of MI or AF. Conclusion: Frequent PACs on Holter monitor represent a significant risk factor for both recurrent events and mortality following CVA/TIA. Further prospective studies should be performed to assess whether these patients may benefit from more aggressive anticoagulation, similar to those with AF.

Statins for acute coronary syndrome.

The early period following the onset of acute coronary syndrome (ACS) represents a critical stage of coronary heart disease, with a high risk of recurrent events and deaths. The short-term effects of early treatment with statins on patient-relevant outcomes in patients suffering from ACS are unclear. This is an update of a review previously published in 2011. To assess the effects, both harms and benefits, of early administered statins in patients with ACS, in terms of mortality and cardiovascular events. We updated the searches of CENTRAL (2013, Issue 3), MEDLINE (Ovid) (1946 to April Week 1 2013), EMBASE (Ovid) (1947 to 2013 Week 14), and CINAHL (EBSCO) (1938 to 2013) on 12 April 2013. We applied no language restrictions. We supplemented the search by contacting experts in the field, by reviewing the reference lists of reviews and editorials on the topic, and by searching trial registries. Randomized controlled trials (RCTs) comparing statins with placebo or usual care, with initiation of statin therapy within 14 days following the onset of ACS, follow-up of at least 30 days, and reporting at least one clinical outcome. Two authors independently assessed risk of bias and extracted data. We calculated risk ratios (RRs) for all outcomes in the treatment and control groups and pooled data using random-effects models. Eighteen studies (14,303 patients) compared early statin treatment versus placebo or no treatment in patients with ACS. The new search did not identify any new studies for inclusion. There were some concerns about risk of bias and imprecision of summary estimates. Based on moderate quality evidence, early statin therapy did not decrease the combined primary outcome of death, non-fatal myocardial infarction, and stroke at one month (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.80 to 1.08) or four months (RR 0.93, 95% CI 0.81 to 1.06) of follow-up when compared to placebo or no treatment. There were no statistically significant risk reductions from statins for total death, total myocardial infarction, total stroke, cardiovascular death, revascularization procedures, and acute heart failure at one month or at four months, although there were favorable trends related to statin use for each of these endpoints. Moderate quality evidence suggests that the incidence of unstable angina was significantly reduced at four months following ACS (RR 0.76, 95% CI 0.59 to 0.96). There were nine individuals with myopathy (elevated creatinine kinase levels more than 10 times the upper limit of normal) in statin-treated patients (0.13%) versus one (0.015%) in the control groups. Serious muscle toxicity was mostly limited to patients treated with simvastatin 80 mg. Based on moderate quality evidence, due to concerns about risk of bias and imprecision, initiation of statin therapy within 14 days following ACS does not reduce death, myocardial infarction, or stroke up to four months, but reduces the occurrence of unstable angina at four months following ACS. Serious side effects were rare.

Improving lipid control following myocardial infarction.

Following a myocardial infarction, lipid-lowering therapy is an established intervention to reduce the risk of recurrent cardiovascular events. Prior studies show a need to improve clinical practice in this area. Here, we review the latest research and perspectives on improving postmyocardial infarction lipid control. Dyslipidemia and myocardial infarction remain leading causes of global disability and premature mortality throughout the world. The processes of care in lipid control involve multiple patient-level, provider-level, and healthcare system-level factors. They can be challenging to coordinate. Recent studies show suboptimal use of early high-intensity statin therapy and overall lipid control following myocardial infarction. Encouragingly, lipid control has improved over the last decade. Implementation science has identified checklists as an effective tool. At the top of the checklist for reducing atherogenic lipids and recurrent event risk postmyocardial infarction is early high-intensity statin therapy. Smoking cessation and participation in cardiac rehabilitation are also priorities, as are lifestyle counseling, promotion of medication adherence, ongoing lipid surveillance, and medication management. Optimizing lipid control could further enhance clinical outcomes after myocardial infarction.

Association between platelet reactivity and circulating platelet-derived microvesicles in patients with acute coronary syndrome

High on-treatment platelet reactivity (HPR) to clopidogrel has been shown to increase the risk of cardiovascular events. Platelet-derived microvesicles (PMVs) may be prothrombotic and contribute to the risk of recurrent events observed in patients with HPR. However, PMVs may also serve as biomarkers and be used to assess platelet function. We investigated the association between platelet responses to clopidogrel (measured by whole blood impedance aggregometry) and circulating PMVs in patients with acute coronary syndrome (ACS). Blood samples were obtained at discharge from 200 patients with ACS who had undergone percutaneous coronary intervention (PCI). All patients were loaded with aspirin and clopidogrel before PCI. ADP-induced whole blood impedance aggregometry and measurement of PMVs were performed. Cut-off values for HPR and other reactivity (i.e. normal on-treatment reactivity, NPR and low on-treatment reactivity, LPR) to clopidogrel were set according to data from large prospective studies. We measured PMVs as phosphatidylserine and CD42a positive vesicles, together with CD62P or CD40L, using flow cytometry. ADP-induced platelet aggregation revealed that approximately 20% of patients had HPR. Levels of PMVs were almost two-fold higher in the HPR group compared with patients without HPR (for both CD42a- and CD62P-positive PMVs, p < 0.01). Furthermore, patients with LPR to clopidogrel had significantly fewer PMVs exposing CD62P than patients with HPR or those with NPR to clopidogrel. Patients with HPR during clopidogrel treatment have elevated levels of circulating PMVs, indicating ongoing platelet activation despite clopidogrel treatment. Moreover, in patients with LPR to clopidogrel, circulating PMV numbers are decreased. Taken together, our data suggest that PMVs are potential biomarkers of antiplatelet responses to clopidogrel. If PMVs also have prognostic value after, ACS should be tested in future studies.

XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis.

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism, poses a substantial clinical risk, and the incidence of these thrombotic-related diseases remains high. Anticoagulation aims to prevent thrombus extension and reduce the risk of recurrent events, particularly fatal pulmonary embolism. In EINSTEIN DVT, rivaroxaban was non-inferior to enoxaparin/vitamin K antagonists for the reduction of recurrent VTE, with a similar safety profile and a net clinical benefit. EINSTEIN EXT investigated patients receiving long-term treatment in whom there was no clear decision about continuing or stopping anticoagulation; rivaroxaban was superior to placebo in the reduction of recurrent VTE, showing an acceptable benefit–risk balance. Rivaroxaban has the potential to replace standard therapy, usually parenteral low molecular weight heparin overlapping with and followed by a vitamin K antagonist, for the treatment of acute symptomatic DVT and the secondary prevention of VTE. As the use of rivaroxaban for DVT treatment increases in clinical practice, a fundamental understanding of its clinical benefits in everyday patient care is essential. XALIA (XArelto for Long-term and Initial Anticoagulation in venous thromboembolism) is a multicentre, prospective, non-interventional, observational study investigating the effectiveness and safety of a single-drug approach with rivaroxaban compared with standard therapy in patients with DVT. The study cohort will include approximately 4800 patients (≥18 years old) with objectively confirmed acute DVT who will be treated for a period of ≥3 months. The primary outcomes will be the incidence of treatment-emergent adverse events (primarily major bleeding), symptomatic recurrent venous thromboembolic events and all-cause mortality. Secondary outcomes include: major cardiovascular events; patient-reported treatment satisfaction and adherence; healthcare resource utilization; reasons for drug switching or interruption of treatment; and adverse events. XALIA will follow an international cohort of patients in more than 20 European countries, and others including Israel and Canada. The first patient was enrolled in June 2012, with results expected in 2015. It is anticipated that XALIA will provide important information on the treatment of DVT in a heterogeneous, unselected patient population in a real-world setting and provide important supplementary information to that obtained from the EINSTEIN DVT phase III study.

Lipoproteins as biomarkers and therapeutic targets in the setting of acute coronary syndrome.

The period following an acute coronary syndrome (ACS) represents a critical time frame with a high risk for recurrent events and death. The pathogenesis of this increase in clinical cardiovascular disease events after ACS is complex, with molecular mechanisms including increased thrombosis and inflammation. Dyslipoproteinemia is common in patients with ACS and predictive of recurrent cardiovascular disease events after presentation with an ACS event. Although randomized clinical trials have provided fairly convincing evidence that high-dose statins reduce the risk of recurrent cardiovascular events after ACS, there remain questions about how aggressively to reduce low-density lipoprotein cholesterol levels in ACS. Furthermore, no other lipid-related interventions have yet been proven to be effective in reducing major cardiovascular events after ACS. Here, we review the relationship of lipoproteins as biomarkers to cardiovascular risk after ACS, the evidence for lipid-targeted interventions, and the potential for novel therapeutic approaches in this arena.

Comparison of Clinical Trial Outcome Patterns in Patients Following Acute Coronary Syndromes and in Patients With Chronic Stable Atherosclerosis

The transition of patients with atherosclerotic vascular disease from the acute phase of the disease to the chronic stable atherosclerosis (CSA) phase has not been well characterized. We sought to compare ischemic and bleeding outcomes in hospitalized patients enrolled in clinical trials of non-ST-elevation acute coronary syndrome (ACS) with patients enrolled in outpatient trials of CSA. The risk for recurrent events will differ between the 2 populations. Patient-level outcome data were evaluated from 3 consecutive trials of patients with ACS with long-term follow-up and 2 trials of patients with CSA. Kaplan-Meier curves were generated for ischemic and bleeding outcomes. In total, 37 370 patients were included in these analyses. Of these, 28 489 (76.2%) were from ACS trials and 8881 (23.8%) from chronic trials. During the first year of follow-up, 1353 deaths, 1081 cardiovascular (CV) deaths, 2113 myocardial infarctions (MIs), and 397 strokes occurred across the trials. Six-month Kaplan-Meier event rates for CV death, MI, or stroke were higher in the ACS trials compared with the CSA trials (8.6% vs 2.7%), as were the 1-year CV death rate (3.6% vs 1.7%) and 1-year rates for GUSTO moderate or severe bleeding (6.0% vs 1.3%). Qualitatively, the Kaplan-Meier curves appear to show an early increased risk as well as a continued increased risk over time. Patients with ACS enrolled while in the hospital appear to have different risk profiles for ischemic and bleeding outcomes compared with outpatients enrolled with CSA, including those patients with ACS after the acute phase.

In-hospital and 1-year outcomes of acute heart failure patients according to presentation (de novo vs. worsening) and ejection fraction. Results from IN-HF Outcome Registry

BackgroundTo investigate the outcomes of hospitalized patients with both de-novo and worsening heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF) (LVEF≥50%), compared to those with reduced LVEF (HFrEF). Methods and resultsWe studied 1669 patients (22.6% HFpEF) hospitalized for acute HF in the prospective multi-center nationwide Italian Network on Heart Failure (IN-HF) Outcome Registry. In all patients LVEF was assessed during hospitalization. De-novo HF presentations constituted 49.6% of HFpEF and 43.1% of HFrEF hospitalizations. All-cause mortality during hospitalization was lower in HFpEF than HFrEF (2.9% vs 6.5%, p=0.01), but this mortality difference was not significant at 1year (19.6% vs 24.4%, p=0.06), even after adjusting for clinical covariates. Similarly, there were no differences in 1-year mortality between HFpEF and HFrEF when compared by cause of death (cardiovascular vs non-cardiovascular) or mode of presentation (worsening HF vs de novo). Rehospitalization rates (all-cause, non-cardiovascular, cardiovascular, HF-related) at 90days and 1year were also similar. Mode of presentation influenced rehospitalizations in HFpEF, where those presenting with worsening HFpEF had higher all-cause (36.8% vs 21.6%, p=0.001), cardiovascular (28.1% vs 14.9%, p=0.002), and HF-related (21.1% vs 7.7%, p=0.0003) rehospitalization rates at 1year compared to those with de novo presentations. ConclusionsOutcomes at 1year following hospitalization for HFpEF are as poor as that of HFrEF. A prior history of HF decompensation or hospitalization identifies patients with HFpEF at particularly high risk of recurrent events. These findings may have implications for clinical practice, quality and process improvements and trial design.

Abstract 61: Safety and Feasibility of Acute Dabigatran Therapy in Minor Ischemic Stroke Patients Without Atrial Fibrillation.

Introduction: Transient Ischemic Attack (TIA) and Minor ischemic stroke (MIS) patients are at high risk for recurrent events. Older anticoagulants are associated with a reduction in recurrent events, but also an increase in hemorrhagic transformation (HT). Dabigatran etexilate (DE), a novel oral anticoagulant that is associated with reduced risk of intracranial bleeding in atrial fibrillation (AF) patients, may be an effective therapy in this population. DE is not indicated within 14 days of ischemic stroke, due to an absence of data. We tested the feasibility and safety of initiating DE therapy within 24 h of TIA/MIS. Methods: We designed a 50 patient single arm open label treatment trial. The primary endpoint was symptomatic HT within 30 days of enrolment. All patients underwent MRI prior to treatment. TIA/MIS patients (NIHSS score ≤3) with a DWI lesion were prospectively treated with DE 150 mg BID (110 mg BID in patients ≥ 80 or if CrCl &lt;40 ml/min). Treatment began within 24 h of onset and continued for 30 days. Patients with known atrial fibrillation (AF) were excluded. Patients were re-imaged at day 7 and 30, with clinical assessment to 90 days. Results: Forty-three of 50 patients have been enrolled to date (March 2012-August 2013). The mean age was 66±12 years and median (IQR) NIHSS was 1 (2). Median baseline DWI volume was 0.89(1.9) ml. The median time from onset to initial DE dose was 18.5 (12.2) h. Therapy was completed in 41 patients and discontinued in two (withdrawal of consent (1) and dysphagia (1)). Two patients died within the 90 day study period, both after completion of DE therapy. No patients experienced systemic bleeding or symptomatic intracranial hemorrhage. One patient had asymptomatic HT (ECASS grade, HI1) on day 7, which resolved by day 30 despite continuing DE. No patients experienced recurrent clinical stroke. New asymptomatic DWI lesions developed in 7 (16%) patients by day 30. Conclusion: These preliminary data suggest DE may be used safely in acute TIA/MIS patients and larger randomized trials are warranted. The low HT rate may make DE an ideal antithrombotic for use immediately after TIA/ischemic stroke.

New antithrombotics for secondary prevention of acute coronary syndrome.

Patients with acute coronary syndrome (ACS) usually receive acetylsalicylic acid plus an adenosine diphosphate (ADP) receptor inhibitor to reduce the long‐term risk of recurrent events. However, patients receiving standard antiplatelet prophylaxis still face a substantial risk of recurrent events. Strategies involving 3 antithrombotic agents with different modes of action have now been tested. In Thrombin Receptor Antagonists for Clinical Event Reduction (TRA‐CER), compared with standard care alone, bleeding complications including intracranial hemorrhage (ICH) were increased with the addition of vorapaxar, without efficacy benefit. In Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA 2°P–TIMI 50), the addition of vorapaxar reduced recurrent events compared with standard care in stable patients with prior myocardial infarction. This study was terminated early in patients with prior stroke owing to excess ICH, though an increased risk of ICH or fatal bleeding was not detected in patients with prior myocardial infarction. The Apixaban for Prevention of Acute Ischemic and Safety Events 2 (APPRAISE‐2) trial of standard‐dose apixaban added to standard care in patients with ACS was also stopped early owing to excess serious bleeding. However, in Rivaroxaban in Combination With Aspirin Alone or With Aspirin and a Thienopyridine in Patients With Acute Coronary Syndromes (ATLAS ACS 2 TIMI 51), fatal bleeding or fatal ICH did not increase with low‐dose rivaroxaban added to low‐dose acetylsalicylic acid‐based standard care compared with standard care alone. In that trial, a significant reduction of recurrent vascular events was shown with 3 antithrombotic regimens compared with standard care. Therefore, depending on drug dose and patient population, further reductions in recurrent vascular events after ACS may be possible in future clinical practice, with a favorable benefit‐risk profile.

The Effect of Sleep Disordered Breathing on the Outcome of Stroke and Transient Ischemic Attack: A Systematic Review

The primary objective was to systematically review the literature on how sleep disordered breathing (SDB) affects recurrence and death among stroke or transient ischemic attack (TIA) patients. A secondary objective was to evaluate how treatment of SDB with continuous positive airway pressure (CPAP) affects the risk of recurrence and death in these patients. Adults (18+) with a stroke or TIA diagnosis were eligible for inclusion. Case groups consisted of patients with a sleep disorder. The outcomes of interest were all-cause mortality, recurrent vascular events, and case fatality. Ten articles covering 1,203 stroke and TIA patients were included in the review. The results generally support a dose-response relationship between severity of SDB and risk of recurrent events and all-cause mortality in stroke and TIA patients. Three small-scale articles with substantial risk of bias evaluated the effects of CPAP therapy, and the results are inconclusive. Data on case fatality is too sparse to be conclusive. Existing studies provide sufficient data to establish obstructive SDB as a negative predictor of all-cause mortality and recurrent vascular events following stroke or TIA. The ability of CPAP treatment to lower the risk of serious adverse outcomes after stroke remains controversial because of substantial risk of bias identified in most of the eligible studies addressing this relation. Additional studies are needed.

Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome

High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS) trials. The primary endpoint was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI. All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI ≥99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI <99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3-5.7; P < 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI (P-trend < 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (<10 ng/L) but hs-cTnI ≥26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI <26 ng/L (9.2% vs 2.9%, P = 0.002). Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.