Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial.

Influenza vaccination reduces the risk of adverse cardiovascular events.The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344).The primary endpoint wasthe composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. Thecumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion,there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccinationbut regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.

Dual-therapy CD34 antibody-covered sirolimus-eluting COMBO stents versus sirolimus-eluting Orsiro stents in patients treated with percutaneous coronary intervention: the three-year outcomes of the SORT OUT X randomised clinical trial.

BACKGROUND: Target lesion failure (TLF) remains an issue with contemporary drug-eluting stents. The dual-therapy sirolimus-eluting and CD34 antibody-coated COMBO stent (DTS) was designed to improve early healing. AIMS: We aimed to compare the 3-year outcomes of the DTS and the sirolimus-eluting Orsiro stent (SES) in all-comer patients treated with percutaneous coronary intervention. METHODS: The SORT OUT X trial is a prospective multicentre randomised clinical trial with a registry-based follow-up comparing DTS and SES. The primary endpoint, TLF, is a composite of cardiac death, myocardial infarction or target lesion revascularisation (TLR). RESULTS: A total of 3,146 patients were randomised to treatment with the DTS (1,578 patients) or the SES (1,568 patients). At 3 years, an intention-to-treat analysis showed that 155 patients (9.8%) who were assigned the DTS and 118 patients (7.5%) who were assigned the SES met the primary endpoint (incidence rate ratio for TLF=1.33, 95% confidence interval: 1.04-1.70; p=0.02). This difference was caused by a significantly higher TLF rate in the DTS group compared to the SES group within the first year, which was mainly explained by a higher incidence of TLR in the DTS group compared to the SES group. Of note, the TLF rates were almost identical from 1 year to 3 years in both stent groups. CONCLUSIONS: At 3 years, the SES was superior to the DTS, mainly because the DTS was associated with an increased risk of TLF within the first year but not from 1 to 3 years. CLINICALTRIALS: gov: NCT03216733.

Time trends in income-related disparity in incidence of acute coronary syndrome.

BACKGROUND: Higher incidence of acute coronary syndrome (ACS), among those with lower income, has been recognized in the most recent decades. Still, there is a paucity of data on temporal changes. This study aims to investigate 20-year time trends in income-related disparity in the incidence of ACS in Denmark. METHODS: This Population-based repeated cross-sectional study included all patients with first-time ACS, aged ≥20 years, registered in the Danish National Patient Registry 1998-2017. Aggregated sociodemographic data for the Danish population was accessed from Statistics Denmark. Yearly incidence rates (IR) and incidence rate ratios (IRR), with the highest-income quartile as a reference, were standardized using cell-specific personal equivalent income according to year, sex and age group with 95% confidence intervals. Interaction analysis was executed for differences in IR of ACS between the lowest- and highest-income quartile over time. RESULTS: A total of 220 070 patients hospitalized with ACS from 1998 to 2017 were identified. The yearly standardized ACS IRs decreased in all income quartiles. However, the IR remained higher in the lowest-income quartile compared to the highest for both men [1998: IRR 1.45 (95% confidence interval, CI 1.39-1.52) and 2017: 1.47 (1.40-1.54)] and women [1998: IRR 1.73 (1.64-1.82) and 2017: 1.76 (1.65-1.88)]. Interaction analysis showed that over the period the difference in IR between the lower- and the highest-income quartile decreased with 1-5 ACS cases per 100 000 person-year. CONCLUSION: Income-related disparity in the incidence of ACS was present in Denmark between 1998 and 2017. Despite a marked overall decrease in the yearly ACS incidence, the extent of income-related disparity remained unchanged.

Temporal trends in socioeconomic disparity in clinical outcomes for patients with acute coronary syndrome.

AIMS: Socioeconomic factors are well-established determinants of clinical outcomes among patients with acute coronary syndrome (ACS) although quality of care has improved the last decades. This study aims to investigate 20-years temporal trends of socioeconomic disparity in 1-year incidence of major adverse cardiac events (MACE) among ACS patients in Denmark. METHODS: This population-based cohort study included all incident ACS patients in the Danish National Patient Registry during 1998-2017. Socioeconomic disparity was assessed by income and educational level. Patients were followed 1-year for MACE; defined as all-cause mortality, recurrent ACS, revascularization, stroke, or cardiac arrest. Adjusted MACE incidence rates (aIR) and hazard rate ratios (aHR) were computed with 95 % confidence intervals (CI) for five-year-periods. Changes in trends were examined from interaction analyses between the HR for five-year-periods and income and education, respectively. RESULTS: The study included 220,887 patients with first-time ACS. The incidence of MACE decreased within all income and education levels. In 1998-2002 the MACE aIR among patients with low income was 885[95%CI:863-907] versus 733[711-756]/1000-person-year among those with high income (aHR: 1.19[95%CI:1.15-1.23]). The aIRs decreased to 506[489-522] and 405[388-423]/1000-person-year, respectively, in 2013-2017 (aHR: 1.23[1.17-1.29]). The aIRs of MACE decreased correspondingly within all educational levels from 1998 to 2002 to 2013-2017. However, the socioeconomic disparity according to the interaction analyses persisted both according to income and educational level. CONCLUSION: Although 1-year clinical outcomes following ACS has improved substantially over the last decades, socioeconomic disparity persisted both according to income and education level.

Clinical impact of influenza vaccination after ST- and non-ST-segment elevation myocardial infarction - insights from the IAMI trial.

BACKGROUND: Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI. METHODS: A total of 2,571 participants were prospectively enrolled in the Influenza vaccination after myocardial infarction (IAMI) trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in eight countries from October 1, 2016 to March 1, 2020. Here we report vaccine effectiveness in the 2,467 participants with ST-segment elevation MI (STEMI, n = 1,348) or non-ST-segment elevation MI (NSTEMI, n = 1,119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification. RESULTS: Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P = .237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at one year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P = .028). CONCLUSIONS: The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI.

Socioeconomic inequity in incidence, outcomes and care for acute coronary syndrome: A systematic review.

BACKGROUND: Socioeconomic inequities in acute coronary syndrome (ACS) epidemiology and care have been reported for at least 30-40 years. However, an up-to-date overview of evidence reflecting current clinical practice is not available. This systematic review aimed to summarize literature published in the last decade, regarding the association between socioeconomic position (SEP), incidence and prevalence of ACS, post-ACS medical care, and mortality. METHODS: The systematic search was performed in PubMed and Embase restricted to publication year (2009-2021), according to predefined methods (PROSPERO: CRD42020197654). Results were classified according to outcomes and socioeconomic exposures, and the risk of bias was evaluated. RESULTS: In total, 181 studies were included, mainly from high-income countries (81%). The majority showed an association between lower SEP (i.e. education, income, occupation, insurance, or composite SEP) and increased ACS incidence (89%)(incidence rate ratios: 1.1-4.7), increased ACS prevalence (88%)(odds ratios (ORs): 1.8-3.9), receiving suboptimal ACS-related medical care (46%)(ORs: 1.1-10.0), or increased post-ACS mortality (71%)(hazard rate ratios: 1.1-4.13). Studies with a lower risk of bias appeared more likely to describe inequity in favor of higher SEP than studies with a higher risk of bias. CONCLUSIONS: Across studies from the last decade, lower SEP is associated with higher risks of ACS, subsequent suboptimal medical care, and mortality among the ACS patients, in particular in studies with a lower risk of bias. This indicates considerable socioeconomic inequity among ACS patients internationally, despite low- and middle-low-income countries being inadequately represented. Thus, efforts are warranted to continuously monitor ACS-related socioeconomic inequity.

Angiographic outcome in patients treated with deferred stenting after ST-segment elevation myocardial infarction-results from DANAMI-3-DEFER.

AIMS: Stent implantation during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) occasionally results in flow disturbances and distal embolization, which may cause adverse clinical outcomes. Deferred stent implantation seems to reduce the impairment on myocardial function, although the mechanisms have not been clarified. We sought to evaluate whether deferred stenting could reduce flow disturbance in patients treated with primary PCI. METHODS AND RESULTS: Patients with STEMI included in the DANAMI-3-DEFER trial were randomized to deferred versus immediate stent implantation. The primary and secondary outcomes of this substudy were the incidences of slow/no reflow and distal embolization. A total of 1205 patients were included. Deferred stenting (n = 594) resulted in lower incidences of distal embolization [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.46-0.98, P = 0.040] and slow/no reflow (OR 0.60, 95%CI 0.37-0.97, P = 0.039). In high-risk subgroups, the protective effect was greatest in patients >65 years of age (slow/no reflow: OR 0.36, 95% CI 0.17-0.72, P = 0.004 and distal embolization: OR 0.34, 95% CI 0.18-0.63, P = 0.001), in patients presenting with occluded culprit artery at admission (slow/no reflow: OR 0.33, 95% CI 0.16-0.65, P = 0.001 and distal embolization: OR 0.54, 95% CI 0.31-0.96, P = 0.036) and in patients with thrombus grade >3 (slow/no reflow: OR 0.37, 95% CI 0.20-0.67, P = 0.001 and distal embolization: OR 0.39, 95% CI 0.24-0.64, P < 0.001) with a significant P for interaction for all. CONCLUSION: Deferred stent implantation reduces the incidences of slow/no reflow and distal embolization, especially in older patients and in those with total coronary occlusion or high level of thrombus burden.

Clinical Heart Failure Among Patients With and Without Severe Mental Illness and the Association With Long-Term Outcomes.

BACKGROUND: Patients with severe mental illness (SMI) including schizophrenia, bipolar disorder, and severe depression have earlier onset of cardiovascular risk factors, predisposing to worse future heart failure (HF) compared with the general population. We investigated associations between the presence/absence of SMI and long-term HF outcomes. METHODS: We identified patients with HF with and without SMI in the Duke University Health System from 2002 to 2017. Using multivariable Cox regression, we examined the primary outcome of all-cause mortality. Secondary outcomes included rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation. RESULTS: We included 20 906 patients with HF (SMI, n=898; non-SMI, n=20 008). Patients with SMI presented clinically 7 years earlier than those without SMI. We observed an interaction between SMI and sex on all-cause mortality (P=0.002). Excess mortality was observed among men with SMI compared with men without SMI (hazard ratio, 1.36 [95% CI, 1.17-1.59]). No association was observed among women with and without SMI (hazard ratio, 0.97 [95% CI, 0.84-1.12]). Rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation were similar between patients with and without SMI (6.1% versus 7.9%, P=0.095). Patients with SMI receiving these procedures for HF experienced poorer prognosis than those without SMI (hazard ratio, 2.12 [95% CI, 1.08-4.15]). CONCLUSIONS: SMI was associated with adverse HF outcome among men and not women. Despite equal access to procedures for HF between patients with and without SMI, those with SMI experienced excess postprocedural mortality. Our data highlight concurrent sex- and mental health-related disparities in HF prognosis, suggesting that patients with SMI, especially men, merit closer follow-up.

Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

BACKGROUND: Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease. METHODS: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis. RESULTS: Because of the COVID-19 pandemic, the data safety and monitoring board recommended to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72 [95% CI, 0.52-0.99]; P=0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 [95% CI, 0.39-0.89]; P=0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 [95% CI, 0.39-0.90]; P=0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 [95% CI, 0.50-1.46]; P=0.57) in the influenza vaccine and placebo groups, respectively. CONCLUSIONS: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02831608.

Randomized Clinical Comparison of the Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Combo Stent With the Sirolimus-Eluting Orsiro Stent in Patients Treated With Percutaneous Coronary Intervention: The SORT OUT X Trial.

BACKGROUND: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody-coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population. METHODS: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021. RESULTS: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26-2.41]; P=0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37-3.61]; P=0.0012). CONCLUSIONS: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03216733.

Association Between ECG Abnormalities and Fatal Cardiovascular Disease Among Patients With and Without Severe Mental Illness.

Background ECG abnormalities are associated with adverse outcomes in the general population, but their prognostic significance in severe mental illness (SMI) remains unexplored. We investigated associations between no, minor, and major ECG abnormalities and fatal cardiovascular disease (CVD) among patients with SMI compared with controls without mental illness. Methods and Results We cross-linked data from Danish nationwide registries and included primary care patients with digital ECGs from 2001 to 2015. Patients had SMI if they were diagnosed with schizophrenia, bipolar disorder, or severe depression before ECG recording. Controls were required to be without any prior mental illness or psychotropic medication use. Fatal CVD was assessed using hazard ratios (HRs) with 95% CIs and standardized 10-year absolute risks. Of 346 552 patients, 10 028 had SMI (3%; median age, 54 years; male, 45%), and 336 524 were controls (97%; median age, 56 years; male, 48%). We observed an interaction between SMI and ECG abnormalities on fatal CVD (P<0.001). Severe mental illness was associated with fatal CVD across no (HR, 2.17; 95% CI, 1.95-2.43), minor (HR, 1.90; 95% CI, 1.49-2.42), and major (HR, 1.40; 95% CI, 1.26-1.55) ECG abnormalities compared with controls. Across age- and sex-specific subgroups, SMI patients with ECG abnormalities but no CVD at baseline had highest standardized 10-year absolute risks of fatal CVD. Conclusions ECG abnormalities conferred a poorer prognosis among patients with SMI compared with controls without mental illness. SMI patients with ECG abnormalities but no CVD represent a high-risk population that may benefit from greater surveillance and risk management.

Concomitant changes in ventricular depolarization and repolarization and long-term outcomes of biventricular pacing.

BACKGROUND: Biventricular (BiV) pacing increases transmural repolarization heterogeneity due to epicardial to endocardial conduction from the left ventricular (LV) lead. However, limited evidence is available on concomitant changes in ventricular depolarization and repolarization and long-term outcomes of BiV pacing. Therefore, we investigated associations of BiV pacing-induced concomitant changes in ventricular depolarization and repolarization with mortality (i.e., LV assist device, heart transplantation, or all-cause mortality) and sustained ventricular arrhythmia endpoints. METHODS: Consecutive BiV-defibrillator recipients with digital preimplantation and postimplantation electrocardiograms recorded between 2006 and 2015 at Duke University Medical Center were included. We calculated changes in QRS duration and corrected JT (JTc) interval and split them by median values. For simplicity, these variables were named QRSdecreased (≤ -12 ms), QRSincreased (> -12 ms), JTcdecreased (≤22 ms), and JTcincreased (> 22 ms) and subsequently used to construct four mutually exclusive groups. RESULTS: We included 528 patients (median age, 68 years; male, 69%). No correlation between changes in QRS duration and JTc interval was observed (P = .295). Compared to QRSdecreased /JTcincreased , increased risk of the composite mortality endpoint was associated with QRSdecreased /JTcdecreased (hazard ratio [HR] = 1.62; 95% confidence interval [CI] = 1.09-2.43), QRSincreased /JTcdecreased (HR = 1.86; 95% CI = 1.27-2.71), and QRSincreased /JTcincreased (HR = 2.25; 95% CI = 1.52-3.35). No QRS/JTc group was associated with excess sustained ventricular arrhythmia risk (P = .400). CONCLUSION: Among BiV-defibrillator recipients, QRSdecreased /JTcincreased was associated with the most favorable long-term survival free of LV assist device, heart transplantation, and sustained ventricular arrhythmias. Our findings suggest that improved electrical resynchronization may be achieved by assessing concomitant changes in ventricular depolarization and repolarization.

Electrocardiogram Characteristics and Their Association With Psychotropic Drugs Among Patients With Schizophrenia.

BACKGROUND: There are limited data on electrocardiogram (ECG) characteristics and their association with psychotropic drugs in schizophrenia. METHODS: Using a cross-sectional design, we included Danish primary care patients with first-time digital ECGs from 2001 to 2015. Patients diagnosed with schizophrenia before ECG recording were matched 1:5 on age, sex, and ECG recording year to controls without psychiatric disease. Multivariable logistic regression was used to compute odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We included 4486 patients with schizophrenia matched with 22 430 controls (median age, 47 years; male, 55%). Between groups, the prevalence of abnormal ECGs was similar (54%, P = .536), but patients with schizophrenia demonstrated higher median heart rate (79 vs 69 beats per minute, P < .001) and Fridericia-corrected QT (QTc) interval (416 vs 412 ms, P < .001) than controls. QTc prolongation was also more prevalent among patients with schizophrenia (3.4% vs 1.1%, P < .001), and so were pathological Q waves (5.3% vs 3.9%, P < .001). Patients with schizophrenia less frequently demonstrated left ventricular hypertrophy (6.1% vs 9.6%, P < .001) and atrial fibrillation or flutter (0.7% vs 1.4%, P < .001). Among patients with schizophrenia only, particularly antipsychotics were associated with abnormal ECGs (OR, 1.20; 95% CI, 1.04-1.39). CONCLUSIONS: Patients with schizophrenia demonstrate a different cardiovascular risk profile than matched controls without psychiatric disease, with higher prevalence of elevated heart rate, QTc prolongation, and pathological Q waves, and lower prevalence of left ventricular hypertrophy and atrial fibrillation or flutter. Particularly antipsychotics were associated with abnormal ECGs. This underscores an integrated care approach when ECG abnormalities are detected in this group.

Long-Term Prognostic Value of Less-Stringent Electrocardiographic Q Waves and Fourth Universal Definition of Myocardial Infarction Q Waves.

BACKGROUND: The Fourth Universal Definition of Myocardial Infarction defines electrocardiographic Q waves as duration ≥30 ms and amplitude ≥1 mm or QS complex in 2 contiguous leads. However, current taskforce criteria may be overly restrictive. Therefore, we investigated the association of isolated, lenient, or strict Q waves with long-term outcome. METHODS: From 2001 to 2015, we included Danish primary care patients with digital electrocardiograms (ECGs) that were evaluated for Q waves. If none occurred, patients had no Q waves. If no other contiguous Q wave occurred, patients had isolated Q waves. If another contiguous Q wave occurred meeting only 1 criterion (≥30 ms and <1 mm or <30 ms and ≥1 mm), patients had lenient Q waves. If another contiguous Q wave occurred, patients had strict Q waves. RESULTS: Of 365,206 patients, 87,957 had isolated, lenient, or strict Q waves (24%; median age, 61 years; male, 48%), and 277,249 had no Q waves (76%; median age, 53 years; male, 42%). Mortality risk was increased with isolated (all-cause adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 1.29-1.37; cardiovascular-cause aHR, 1.78; 95% CI, 1.70-1.87), lenient (all-cause aHR, 1.41; 95% CI, 1.33-1.50; cardiovascular-cause aHR, 1.78; 95% CI, 1.63-1.94), or strict (all-cause aHR, 1.64; 95% CI, 1.57-1.72; cardiovascular-cause aHR, 2.70; 95% CI, 2.52-2.89) Q waves compared with no Q waves. Highest mortality risk was associated with lenient or strict Q waves in anteroseptal leads. CONCLUSIONS: This large contemporary analysis suggests that less-stringent Q-wave criteria carry prognostic value in predicting adverse outcome among primary care patients.

Everolimus-Eluting Versus Biolimus-Eluting Coronary Stent Implantation in Patients With and Without Diabetes Mellitus.

Diabetes mellitus is associated with a higher risk of target lesion revascularization after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus, treated with everolimus-eluting stents (EES; Synergy; Boston Scientific, Marlborough, Massachusetts) or biolimus-eluting stents (BES; BioMatrix NeoFlex; Biosensors Interventional Technologies Pte Ltd., Singapore). In total, 2,764 patients were randomized to stent implantation with EES (n = 1,385, diabetes: n = 250) or the BES (n = 1,379, diabetes: n = 262), stratified by gender and diabetes. The primary end point, target lesion failure (TLF), was a composite of cardiac death, target-lesion myocardial infarction, or target lesion revascularization at 12 months. Secondary end points included individual components of TLF, all-cause death, and stent thrombosis. TLF was 2.1% lower in the EES versus the BES groups in patients with diabetes (3.6% vs 5.7%; rate ratios 0.61, 95% confidence interval [CI] 0.27 to 1.41) and similar in patients without diabetes (4.1% vs 4.0%; rate ratios 0.99, 95% CI 0.66 to 1.51). In patients with diabetes, the point estimates of the individual components of TLF also favored the EES but CIs were wide. No interaction between stent type and presence of diabetes was found. The current subgroup analysis found that a thin-strut EES as compared with a thicker strut BES had a numerically lower TLF rate in patients with diabetes, but the subgroup analysis was underpowered for definite conclusions.

Predicting stroke in patients without atrial fibrillation.

BACKGROUND: Only few studies in selected cohorts have examined whether the CHA2 DS2 -VASc score can predict the risk of atrial fibrillation and thromboembolic events in patients without atrial fibrillation. MATERIALS AND METHODS: Patients with coronary angiography performed between 2004 and 2012 were grouped according to CHA2 DS2 -VASc score. We excluded patients with atrial fibrillation, anticoagulant therapy and follow-up <30 days. The endpoints were atrial fibrillation and a composite of ischaemic stroke, transient ischaemic attack and systemic embolism. Event rates per 100 person-years were estimated for each CHA2 DS2 -VASc score (0, 1, 2, 3, 4, and >4). Incidence rate ratios were calculated using low-risk patients (CHA2 DS2 -VASc score 0 in males or 1 in females) as reference. RESULTS: In total, 78 233 patients were included with group sizes varying between 8299 (CHA2 DS2 -VASc >4) and 19 882 (CHA2 DS2 -VASc 2). An increasing CHA2 DS2 -VASc score was significantly associated with a future diagnosis of atrial fibrillation (P for trend <0.0001) and an incremental risk of ischaemic stroke, transient ischaemic attack, systemic embolism (P for trend <0.0001) and all-cause death (P for trend <0.0001). Patients with a CHA2 DS2 -VASc score of 3 had a rate of ischaemic stroke/transient ischaemic attack/systemic embolism of 1.30 per 100 person-years. CONCLUSIONS: Among patients undergoing coronary angiography, the CHA2 DS2 -VASc score predicted a future diagnosis of atrial fibrillation and the composite risk of ischaemic stroke, transient ischaemic attack or systemic embolism in patients without atrial fibrillation. A CHA2 DS2 -VASc score of 3 was associated with a risk that would justify prophylactic oral anticoagulation treatment in a patient with atrial fibrillation.

Should the Presence or Extent of Coronary Artery Disease be Quantified in the CHA2DS2-VASc Score in Atrial Fibrillation? A Report from the Western Denmark Heart Registry.

BACKGROUND: Patients with atrial fibrillation (AF) have an increased risk of ischaemic stroke. The risk can be predicted by the CHA2DS2-VASc score, in which the vascular component refers to previous myocardial infarction, peripheral artery disease and aortic plaque, whereas coronary artery disease (CAD) is not included. OBJECTIVES: This article explores whether CAD per se or extent provides independent prognostic information of future stroke among patients with AF. MATERIALS AND METHODS: Consecutive patients with AF and coronary angiography performed between 2004 and 2012 were included. The endpoint was a composite of ischaemic stroke, transient ischaemic attack and systemic embolism. The risk of ischaemic events was estimated according to the presence and extent of CAD. Incidence rate ratios (IRR) were calculated in reference to patients without CAD and adjusted for parameters included in the CHA2DS2-VASc score and treatment with anti-platelet agents and/or oral anticoagulants. RESULTS: Of 96,430 patients undergoing coronary angiography, 12,690 had AF. Among patients with AF, 7,533 (59.4%) had CAD. Mean follow-up was 3 years. While presence of CAD was an independent risk factor for the composite endpoint (adjusted IRR, 1.25; 1.06-1.47), extent of CAD defined as 1-, 2-, 3- or diffuse vessel disease did not add additional independent risk information. CONCLUSION: Presence, but not extent, of CAD was an independent risk factor of the composite thromboembolic endpoint beyond the components already included in the CHA2DS2-VASc score. Consequently, we suggest that significant angiographically proven CAD should be included in the vascular disease criterion in the CHA2DS2-VASc score.

Randomized clinical comparison of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent with the sirolimus-eluting Orsiro stent in patients treated with percutaneous coronary intervention: Rationale and study design of the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X trial.

BACKGROUND: The Combo stent (OrbusNeich, Hoevelaken, the Netherlands) combining an abluminal, bioabsorbable polymer eluting sirolimus with a luminal CD34+ antibody to capture endothelial progenitor cells has been developed to further improve safety and efficacy of coronary interventions. We have designed a large-scale registry-based randomized clinical trial to compare the Combo stent to the Orsiro stent (Biotronik, Bülach, Switzerland) in patients undergoing percutaneous coronary intervention. METHODS: The SORT OUT X study will randomly assign 3,140 patients to treatment with Combo or Orsiro stents at 3 sites in Western Denmark. Patients are eligible if they are ≥18 years old, have chronic stable coronary artery disease or acute coronary syndromes, and have ≥1 coronary lesion with >50% diameter stenosis requiring treatment with a drug-eluting stent. The primary end point target lesion failure is a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 12 months. Clinically driven event detection will be derived from validated Danish registries. An event rate of 4.2% is assumed in each stent group. With a sample size of 1,570 patients in each treatment arm, a 2-group large-sample normal approximation test of proportions with a 1-sided 5% significance level will have 90% power to detect noninferiority of the Combo stent compared with the Orsiro stent with a predetermined noninferiority margin of 2.1%. CONCLUSION: The SORT OUT X trial will determine whether the dual-therapy Combo stent is noninferior to the Orsiro stent with respect to clinically driven events (ClinicalTrials.govNCT03216733).

Randomized clinical trial: the impact of gastrointestinal risk factor screening and prophylactic proton pump inhibitor therapy in patients receiving dual antiplatelet therapy.

OBJECTIVE: Dual antiplatelet therapy reduces the risk of ischemic complications after acute coronary syndrome, but increases the risk of bleeding including upper gastrointestinal bleeding (UGIB).The aim of this study was to examine the effect of screening for risk of UGIB and prophylactic proton pump inhibitor (PPI) treatment in dual-antiplatelet-treated patients at risk of UGIB and to assess the significance of dual antiplatelet therapy compliance for cardiovascular events. PATIENTS AND METHODS: In a register-based randomized-controlled trial, 2009 patients were included at the time of first percutaneous coronary intervention and randomized to either screening or control. Screened high-risk patients were prescribed pantoprazole 40 mg during the 1-year after percutaneous coronary intervention. RESULTS: The incidence of UGIB was 0.8 versus 1.3% in screened patients and controls, respectively (P=0.381).Significantly fewer screened patients (5.4%) than controls (8.0%) underwent upper gastrointestinal endoscopy (P=0.026). Screened patients (2.9%) had significantly fewer events of unstable angina pectoris than controls (4.7%) (P=0.036) and a higher compliance to dual antiplatelet therapy (88.3 vs. 85.0%) (P=0.035), but no statistically difference was observed in the incidences of myocardial infarction and all-cause mortality (1.0 vs. 1.5%) (P=0.422). CONCLUSION: Screening for risk factors for UGIB and subsequent prophylactic PPI treatment did not significantly reduce the incidence of UGIB. Prescription of PPI was associated with a higher compliance with dual antiplatelet therapy and decreases the risk of recurrent cardiovascular events.