Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Implementation of Ticagrelor Reduced Mortality in Routine Clinical Care: Evidence From a Natural Experiment Including 109 995 Patients With Myocardial Infarction in Sweden.

Background Effectiveness estimates from observational studies on ticagrelor use in routine clinical care are conflicting, with some contrary to the results of the pivotal randomized controlled trial of ticagrelor in acute coronary syndrome. The aim of this study was to estimate the effect of implementing and using ticagrelor in routine clinical care in patients with myocardial infarction using a natural experimental approach. Methods and Results This is a retrospective cohort study including patients hospitalized for myocardial infarction in Sweden between 2009 and 2015. The study exploited differences in the timing and speed of ticagrelor implementation between treatment centers as a source of random treatment assignment. The effect of implementing and using ticagrelor was estimated based on the admitting center's likelihood of treating patients with ticagrelor, measured as the proportion of patients treated in the 90 days before patient admission. The main outcome was 12-month mortality. The study included 109 955 patients, of whom 30 773 were treated with ticagrelor. Being admitted to a treatment center with higher past ticagrelor use was associated with a reduction in 12-month mortality (2.5 percentage points for 100% versus 0% past use [95% CI, 0.2-4.8]). The results are in line with the findings from the ticagrelor pivotal trial. Conclusions Using a natural experiment, this study finds that the implementation and use of ticagrelor in routine clinical care has reduced 12-month mortality in patients admitted to the hospital with myocardial infarction in Sweden and supports the external validity of randomized evidence on ticagrelor effectiveness.

Long-term antithrombotic therapy after coronary artery bypass grafting in patients with preoperative atrial fibrillation. A nationwide observational study from the SWEDEHEART registry.

AIMS: To provide data guiding long-term antithrombotic therapy after coronary artery by-pass grafting (CABG) in patients with preoperative atrial fibrillation (AF). METHODS AND RESULTS: From the SWEDEHEART registry, we included all patients, between January 2006 and September 2016, with preoperative AF and CHA2DS2-VASC score ≥2, undergoing CABG. Based on dispensed prescriptions 12 to 18 months after CABG, patients were divided in 3 groups: use of platelet inhibitors (PI) only, oral anticoagulant (OAC) only or a combination of OAC + PI. Outcomes were: Major adverse cardiac and cerebrovascular events (MACCE, [all-cause death, myocardial infarction, or stroke]), net adverse clinical events (NACE, [MACCE or bleeding]) and the individual components of NACE. Inverse probability of treatment weighting was used to adjust for the non-randomized study design. Among 2,564 patients, 1,040 (41%) were treated with PI alone, 1,064 (41%) with OAC alone, and 460 (18%) with PI + OAC. Treatment with PI alone was associated with higher risk for MACCE (adjusted HR 1.43, 95% CI 1.09-1.88), driven by higher risk for stroke and MI, compared with OAC alone. Treatment with PI + OAC, was associated with higher risk for NACE (adjusted HR 1.40, 95% CI 1.06-1.85), driven by higher risk for bleeds, compared with OAC alone. CONCLUSION: In this real-world observational study, a high proportion of patients with AF, undergoing CABG, did not receive a long-term OAC therapy. Treatment with OAC alone was associated with a net clinical benefit, compared with PI alone or PI + OAC.

[Clinical Frailty Scale - a proxy estimate of biological age]. / Clinical frailty scale ­ skörhet är ett sätt att skatta biologisk ålder.

The term frailty denotes a multi-dimensional syndrome characterised by reduced physiological reserves and increased vulnerability. Frailty may be used as a marker of biological age, distinct from chronological age. There are several instruments for frailty assessment. The Clinical Frailty Scale (CFS) is probably the most commonly used in the acute care context. It is a 9-level scale, derived from the accumulated deficit model of frailty, which combines comorbidity, disability, and cognitive impairment. The CFS assessment is fast and easy to implement in daily clinical practice. The CFS is relevant for risk stratification, and may also be used as a screening instrument to identify frail patients suitable for further geriatric evaluation, i.e. a comprehensive geriatric assessment (CGA). By providing information on long-term prognosis, it may improve informed decision-making on an individual basis.

Clinical decision support for familial hypercholesterolemia (CDS-FH): Rationale and design of a cluster randomized trial in primary care.

BACKGROUND: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder with high risk of premature atherosclerotic cardiovascular disease and death. Clinical decision support (CDS) systems have the potential to aid in the identification and management of patients with FH. Prior studies using computer-based systems to screen patients for FH have shown promising results, but there has been no randomized controlled trial conducted. The aim of the current cluster randomized study is to evaluate if a CDS can increase the identification of FH. METHODS: We have developed a CDS integrated in the electronic health records that will be activated in patients with elevated cholesterol levels (total cholesterol >8 mmol/L or low-density lipoprotein-cholesterol >5.5 mmol/L, adjusted for age, ongoing lipid lowering therapy and presence of premature coronary artery disease) at increased risk for FH. When activated, the CDS will urge the physician to send an automatically generated referral to the local lipid clinic for further evaluation. To evaluate the effects of the CDS, all primary care clinics will be cluster randomized 1:1 to either CDS intervention or standard care in a Swedish region with almost 500,000 inhabitants. The primary endpoint will be the number of patients diagnosed with FH at 30 months. Resource use and long-term health consequences will be estimated to assess the cost-effectiveness of the intervention. CONCLUSION: Despite increasing awareness of FH, the condition remains underdiagnosed and undertreated. The present study will investigate whether a CDS can increase the number of patients being diagnosed with FH.

Uninterrupted Oral Anticoagulant Therapy in Patients Undergoing Unplanned Percutaneous Coronary Intervention.

OBJECTIVES: This study sought to compare interrupted and uninterrupted oral anticoagulant therapy (I-OAC vs. U-OAC) in patients on OAC undergoing percutaneous coronary intervention. BACKGROUND: There is a paucity of data regarding the optimal peri-procedural management of OAC-treated patients. METHODS: In the SWEDEHEART registry, all patients on OAC who were admitted acutely and underwent percutaneous coronary intervention or coronary angiography with a diagnostic procedure, from 2005 to 2017, were included. Outcomes were major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction, or stroke) and bleeds at 120 days. Propensity score was used to adjust for the nonrandomized treatment selection. RESULTS: The study included 6,485 patients: 3,322 in the I-OAC group and 3,163 in the U-OAC group. The cumulative incidence of MACCE was 8.2% (269 events) versus 8.2% (254 events) in the I-OAC and the U-OAC groups, respectively. The adjusted risk for MACCE did not differ between the groups (I-OAC vs. U-OAC hazard ratio: 0.89; 95% confidence interval: 0.71 to 1.12). Similarly, no difference was found in the risk for MACCE or bleeds (12.6% vs. 12.9%, adjusted hazard ratio: 0.87; 95% confidence interval: 0.70 to 1.07). The risk for major or minor in-hospital bleeds did not differ between the groups. However, U-OAC was associated with a significantly shorter duration of hospitalization: 4 (3 to 7) days versus 5 (3 to 8) days; p < 0.01. CONCLUSIONS: I-OAC and U-OAC were associated with equivalent risk for MACCE and bleeding complications. An U-OAC strategy was associated with shorter length of hospitalization. These data support U-OAC as the preferable strategy in patients on OAC undergoing coronary intervention.

Long term risk and costs of bleeding in men and women treated with triple antithrombotic therapy-An observational study.

OBJECTIVES: Bleeding is the most common non-ischemic complication in patients with coronary revascularisation procedures, associated with prolonged hospitalisation and increased mortality. Many factors predispose for bleeds in these patients, among those sex. Anyhow, few studies have characterised the population receiving triple antithrombotic therapy (TAT) as well as long term bleeds from a sex perspective. We investigated the one year rate of bleeds in patients receiving TAT, potential sex disparities and premature discontinuation of TAT. We also assessed health care costs in bleeders vs non-bleeders. SETTING: Three hospitals in the County of Östergötland, Sweden during 2009-2015. PARTICIPANTS: All patients discharged with TAT registered in the SWEDEHEART registry. PRIMARY AND SECONDARY OUTCOME MEASURES: All bleeds receiving medical attention during one-year follow-up were collected by retrieving relevant information about each patient from medical records. Resource use associated with bleeds was assigned unit cost to estimate the health care costs associated with bleeding episodes. RESULTS: Among 272 patients, 156 bleeds occurred post-discharge, of which 28.8% were gastrointestinal. In total 54.4% had at least one bleed during or after the index event and 40.1% bled post discharge of whom 28.7% experienced a TIMI major or minor bleeding. Women discontinued TAT prematurely more often than men (52.9 vs 36.1%, p = 0.01) and bled more (48.6 vs. 37.1%, p = 0.09). One-year mean health care costs were EUR 575 and EUR 5787 in non-bleeding and bleeding patients, respectively. CONCLUSION: The high bleeding incidence in patients with TAT, especially in women, is a cause of concern. There is a need for an adequately sized randomised, controlled trial to determine a safe but still effective treatment for these patients.

The transluminal attenuation gradient does not add diagnostic accuracy to coronary computed tomography.

BACKGROUND: A method for improving the accuracy of coronary computed tomography angiography (CCTA) is highly sought after as it would help to avoid unnecessary invasive coronary angiographies. Measurement of the transluminal attenuation gradient (TAG) has been proposed as an alternative to other existing methods, i.e. CT perfusion and CT fractional flow reserve (FFR). PURPOSE: To evaluate the incremental value of three types of TAG in high-pitch spiral CCTA with invasive FFR measurements as reference. MATERIAL AND METHODS: TAG was measured using two semi-automatic methods and one manual method. A receiver operating characteristic (ROC) analysis was made to determine the usefulness of TAG alone as well as TAG combined with CCTA for detection of significant coronary artery stenoses defined by an invasive FFR value ≤0.80. RESULTS: A total of 51 coronary vessels in 37 patients were included in this retrospective study. Hemodynamically significant stenoses were found in 13 vessels according to FFR. The ROC analysis TAG alone resulted in areas under the curve (AUCs) of 0.530 and 0.520 for the semi-automatic TAG and 0.557 for the manual TAG. TAG and CCTA combined resulted in AUCs of 0.567, 0.562 for semi-automatic TAG, and 0.569 for the manual TAG. CONCLUSION: The results from our study showed no incremental value of TAG measured in single heartbeat CCTA in determining the severity of coronary artery stenosis degrees.

Sex differences in platelet reactivity in patients with myocardial infarction treated with triple antiplatelet therapy - results from assessing platelet activity in coronary heart disease (APACHE).

)Several earlier studies have reported increased risk of bleeding in women with myocardial infarction, (MI) compared to men. The reasons for the observed difference are incompletely understood, but one suggested explanation has been excess dosing of antithrombotic drugs in women. The aim of this prospective observational study was to assess sex differences in platelet activity in patients treated with three different platelet inhibitors. We recruited 125 patients (37 women and 88 men) with MI, scheduled for coronary angiography. All patients received clopidogrel and aspirin. A subgroup of patients received glycoprotein (GP) IIb/IIIa-inhibitor. Platelet aggregation in whole blood was assessed at several time points, using impedance aggregometry. Soluble P-selectin was measured 3 days after admission. There were no significant differences between women and men in baseline features or comorbidities except higher frequency of diabetes, lower hemoglobin value, and lower estimated glomerular filtration rate, in women on admission. We observed significantly more in-hospital bleeding events in women compared to men (18.9% vs. 6.8%, p = .04). There were no differences in platelet aggregation using three different agonists, reflecting treatment effect of GPIIb/IIIa-inhibitors, clopidogrel, and aspirin, 6-8 hours, 3 days, 7-9 days, or 6 months after loading dose. Moreover, there was no significant difference in soluble P-selectin. The main finding of this study was a consistent lack of difference between the sexes in platelet aggregation, using three different agonists at several time-points. Our results do not support excess dosing of anti-platelet drugs as a major explanation for increased bleeding risk in women.

Bleeding complications with clopidogrel or ticagrelor in ST-elevation myocardial infarction patients - A real life cohort study of two treatment strategies.

INTRODUCTION: Dual antiplatelet therapy (DAPT), including potent P2Y12 inhibition after ST-elevation myocardial infarction (STEMI) is recommended in clinical guidelines. However, bleeding complications are common, and associated with worse outcomes. The aim of this study was to assess incidence of bleeding events with a clopidogrel-based compared to a ticagrelor-based DAPT strategy, in a real world population. Secondary aims were to assess ischemic complications and mortality. METHODS AND RESULTS: We identified 330 consecutive STEMI patients with a clopidogrel-based and 330 with a ticagrelor-based DAPT strategy. Patients medical records were searched for bleeding and ischemic complications, over 6 months follow-up.The two groups were well balanced in baseline characteristics, age (69 years inboth groups), sex (31% vs 32% females), history of diabetes (19% vs 21%), hypertension (43% in both) and MI (17% vs 15%). There was no difference in CRUSADE bleeding score (28 vs 29). After discharge, there were more than twice as many bleeding events with a ticagrelor-based compared with a clopidogrel-based strategy (13.3% vs. 6.5%, p = 0.005). Bleeding events included significantly more severe bleeding complications (TIMI major/minor [5.8 vs 1.0, p = 0.001]) during the ticagrelor-based period. There was no significant difference in the composite of death, MI or stroke (7.8% vs 7.1%, p = 0.76). CONCLUSIONS: In this observational study, a ticagrelor-based DAPT strategy was associated with significantly more bleeding complications, without any significant change in death, MI or stroke. Larger studies are needed to determine whether bleeding complications off-sets benefits with a more potent DAPT strategy in older and more comorbid real-life patients.

Subcategorizing the Expected Value of Perfect Implementation to Identify When and Where to Invest in Implementation Initiatives.

Purpose. Clinical practice variations and low implementation of effective and cost-effective health care technologies are a key challenge for health care systems and may lead to suboptimal treatment and health loss for patients. The purpose of this work was to subcategorize the expected value of perfect implementation (EVPIM) to enable estimation of the absolute and relative value of eliminating slow, low, and delayed implementation. Methods. Building on the EVPIM framework, this work defines EVPIM subcategories to estimate the expected value of eliminating slow, low, or delayed implementation. The work also shows how information on regional implementation patterns can be used to estimate the value of eliminating regional implementation variation. The application of this subcategorization is illustrated by a case study of the implementation of an antiplatelet therapy for the secondary prevention after myocardial infarction in Sweden. Incremental net benefit (INB) estimates are based on published cost-effectiveness assessments and a threshold of SEK 250,000 (£22,300) per quality-adjusted life year (QALY). Results. In the case study, slow, low, and delayed implementation was estimated to represent 22%, 34%, and 44% of the total population EVPIM (2941 QALYs or SEK 735 million), respectively. The value of eliminating implementation variation across health care regions was estimated to 39% of total EVPIM (1138 QALYs). Conclusion. Subcategorizing EVPIM estimates the absolute and relative value of eliminating different parts of suboptimal implementation. By doing so, this approach could help decision makers to identify which parts of suboptimal implementation are contributing most to total EVPIM and provide the basis for assessing the cost and benefit of implementation activities that may address these in future implementation of health care interventions.

Evaluation of an AI-based, automatic coronary artery calcium scoring software.

OBJECTIVES: To evaluate an artificial intelligence (AI)-based, automatic coronary artery calcium (CAC) scoring software, using a semi-automatic software as a reference. METHODS: This observational study included 315 consecutive, non-contrast-enhanced calcium scoring computed tomography (CSCT) scans. A semi-automatic and an automatic software obtained the Agatston score (AS), the volume score (VS), the mass score (MS), and the number of calcified coronary lesions. Semi-automatic and automatic analysis time were registered, including a manual double-check of the automatic results. Statistical analyses were Spearman's rank correlation coefficient (⍴), intra-class correlation (ICC), Bland Altman plots, weighted kappa analysis (κ), and Wilcoxon signed-rank test. RESULTS: The correlation and agreement for the AS, VS, and MS were ⍴ = 0.935, 0.932, 0.934 (p < 0.001), and ICC = 0.996, 0.996, 0.991, respectively (p < 0.001). The correlation and agreement for the number of calcified lesions were ⍴ = 0.903 and ICC = 0.977 (p < 0.001), respectively. The Bland Altman mean difference and 1.96 SD upper and lower limits of agreements for the AS, VS, and MS were - 8.2 (- 115.1 to 98.2), - 7.4 (- 93.9 to 79.1), and - 3.8 (- 33.6 to 25.9), respectively. Agreement in risk category assignment was 89.5% and κ = 0.919 (p < 0.001). The median time for the semi-automatic and automatic method was 59 s (IQR 35-100) and 36 s (IQR 29-49), respectively (p < 0.001). CONCLUSIONS: There was an excellent correlation and agreement between the automatic software and the semi-automatic software for three CAC scores and the number of calcified lesions. Risk category classification was accurate but showing an overestimation bias tendency. Also, the automatic method was less time-demanding. KEY POINTS: • Coronary artery calcium (CAC) scoring is an excellent candidate for artificial intelligence (AI) development in a clinical setting. • An AI-based, automatic software obtained CAC scores with excellent correlation and agreement compared with a conventional method but was less time-consuming.

Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: A Subanalysis of the ATLANTIC Trial.

BACKGROUND: Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated. METHODS: 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days. RESULTS: Compared with no GPI (n = 930), routine GPI (n = 525) or bailout GPI (n = 175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p = 0.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32-6.64; p = 0.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88-3.61; p = 0.92). CONCLUSION: Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation.

Combined association of key risk factors on ischaemic outcomes and bleeding in patients with myocardial infarction.

OBJECTIVE: In patients with myocardial infarction (MI), risk factors for bleeding and ischaemic events tend to overlap, but the combined effects of these factors have scarcely been studied in contemporary real-world settings. We aimed to assess the combined associations of established risk factors using nationwide registries. METHODS: Using the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry, patients with invasively managed MI in 2006-2014 were included. Six factors were assessed in relation to cardiovascular death (CVD)/MI/stroke, and major bleeding: age ≥65, chronic kidney disease, diabetes, multivessel disease, prior bleeding and prior MI. RESULTS: We studied 100 879 patients, of whom 20 831 (20.6%) experienced CVD/MI/stroke and 5939 (5.9%) major bleeding, during 3.6 years median follow-up. In adjusted Cox models, all factors were associated with CVD/MI/stroke, and all but prior MI were associated with major bleeding. The majority (53.5%) had ≥2 risk factors. With each added risk factor, there was a marked but gradual increase in incidence of the CVD/MI/stroke. This was seen also for major bleeding, but to a lesser extent, largely driven by prior bleeding as the strongest risk factor. CONCLUSIONS: The majority of patients with MI had two or more established risk factors. Increasing number of risk factors was associated with higher rate of ischaemic events. When excluding patients with prior major bleeding, bleeding incidence rate increased only minimally with increasing number of risk factors. The high ischaemic risk in those with multiple risk factors highlights an unmet need for additional preventive measures.

Impact of ischaemic heart disease severity and age on risk of cardiovascular outcome in diabetes patients in Sweden: a nationwide observational study.

OBJECTIVES: To compare short-term cardiovascular (CV) outcome in type 2 diabetes (T2D) patients without ischaemic heart disease (IHD), with IHD but no prior myocardial infarction (MI), and those with prior MI; and assess the impact on risk of age when initiating first-time glucose-lowering drug (GLD). DESIGN: Cohort study linking morbidity, mortality and medication data from Swedish national registries. PARTICIPANTS: First-time users of GLD during 2007-2016. OUTCOMES: Predicted cumulative incidence for the CV outcome (MI, stroke and CV mortality) was estimated. A Cox model was developed where age at GLD start and CV risk was modelled. RESULTS: 260 070 first-time GLD users were included, 221 226 (85%) had no IHD, 16 294 (6%) had stable IHD-prior MI and 22 550 (9%) had IHD+MI. T2D patients without IHD had a lower risk of CV outcome compared with the IHD populations (±prior MI), (3-year incidence 4.78% vs 5.85% and 8.04%). The difference in CV outcome was primarily driven by a relative greater MI risk among the IHD patients. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger (<60 years) patients had a relative greater risk compared with older patients. CONCLUSIONS: T2D patients without IHD had a lower risk of the CV outcome compared with the T2D populations with IHD, primarily driven by a greater risk of MI. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger patients had a relative greater risk compared with older patients. Our findings suggest that intense risk prevention should be the key strategy in the management of T2D patients, especially for younger patients.

Clinical impact and predictors of complete ST segment resolution after primary percutaneous coronary intervention: A subanalysis of the ATLANTIC Trial.

BACKGROUND: In the ATLANTIC (Administration of Ticagrelor in the catheterization laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery) trial the early use of aspirin, anticoagulation, and ticagrelor coupled with very short medical contact-to-balloon times represent good indicators of optimal treatment of ST-elevation myocardial infarction and an ideal setting to explore which factors may influence coronary reperfusion beyond a well-established pre-hospital system. METHODS: This study sought to evaluate predictors of complete ST-segment resolution after percutaneous coronary intervention in ST-elevation myocardial infarction patients enrolled in the ATLANTIC trial. ST-segment analysis was performed on electrocardiograms recorded at the time of inclusion (pre-hospital electrocardiogram), and one hour after percutaneous coronary intervention (post-percutaneous coronary intervention electrocardiogram) by an independent core laboratory. Complete ST-segment resolution was defined as ≥70% ST-segment resolution. RESULTS: Complete ST-segment resolution occurred post-percutaneous coronary intervention in 54.9% ( n=800/1456) of patients and predicted lower 30-day composite major adverse cardiovascular and cerebrovascular events (odds ratio 0.35, 95% confidence interval 0.19-0.65; p<0.01), definite stent thrombosis (odds ratio 0.18, 95% confidence interval 0.02-0.88; p=0.03), and total mortality (odds ratio 0.43, 95% confidence interval 0.19-0.97; p=0.04). In multivariate analysis, independent negative predictors of complete ST-segment resolution were the time from symptoms to pre-hospital electrocardiogram (odds ratio 0.91, 95% confidence interval 0.85-0.98; p<0.01) and diabetes mellitus (odds ratio 0.6, 95% confidence interval 0.44-0.83; p<0.01); pre-hospital ticagrelor treatment showed a favorable trend for complete ST-segment resolution (odds ratio 1.22, 95% confidence interval 0.99-1.51; p=0.06). CONCLUSIONS: This study confirmed that post-percutaneous coronary intervention complete ST-segment resolution is a valid surrogate marker for cardiovascular clinical outcomes. In the current era of ST-elevation myocardial infarction reperfusion, patients' delay and diabetes mellitus are independent predictors of poor reperfusion and need specific attention in the future.

Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction.

There is a large inter-individual variation in response to clopidogrel treatment, and previous studies have indicated higher risk of thrombotic events in those with high residual platelet reactivity (HPR). Less is known about individual variation over time. The aim of this prospective cohort study was to investigate intra-individual variation in platelet reactivity. Platelet aggregation in whole blood was assessed in 77 patients, at 3 days, 8 days and 6 months after admission for acute myocardial infarction and loading dose of clopidogrel. All patients were treated with aspirin and clopidogrel through 6-month follow-up. We found a significant increase in median ADP-stimulated aggregation from third to eighth day (195 vs. 250 AU*min, p-value = 0.001) but not from day 8 to 6 months (250 vs. 223 AU*min, p-value = 0.666). There was no significant change in the overall rate of HPR (15.6% vs 20.8%, p-value 0.503) or low platelet reactivity (LPR) (37.7% vs 33.8%, p-value = 0.609) from day 8 to 6-month follow-up. In contrast, more than one in four changed HPR status, 15.6% from non-HPR to HPR and 10.4% HPR to non-HPR. A shift in LPR status appeared even more frequent, occurring in about one of three patients. In spite of similar median aggregation and rate of HPR during 6-month follow-up, about one in four of the patients changed HPR status and one in three changed LPR status. This may be important information for a concept of risk stratification based on a single aggregation value early after an acute coronary syndromes.

Long-term prognostic value of coronary computed tomography angiography in chest pain patients.

BACKGROUND: Coronary computed tomography angiography (CCTA) is increasingly used to detect coronary artery disease (CAD), but long-term follow-up studies are still scarce. PURPOSE: To evaluate the prognostic value of CCTA in patients with suspected CAD. MATERIAL AND METHODS: A total of 1205 consecutive CCTA patients with chest pain were classified as normal coronary arteries, non-obstructive CAD, or obstructive CAD. The primary outcome was major adverse cardiac event (MACE), defined as a composite outcome including cardiac death, myocardial infarction, unstable angina pectoris, or late revascularization (after >90 days). RESULTS: Over 7.5 years follow-up (median = 3.1 years), Kaplan-Meier estimates demonstrated a MACE in 1.0%, 4.6%, and 20.7% in normal coronary arteries, non-obstructive CAD, and obstructive CAD, respectively. Log rank test for pairwise comparisons showed significant differences between non-obstructive CAD and normal coronary arteries ( P = 0.023) and between obstructive CAD and normal coronary arteries ( P < 0.001). In a multivariable analysis, adjusting for classical risk factors, non-obstructive CAD and obstructive CAD were independent predictors of MACE, with hazard ratios (HR) of 3.22 ( P = 0.041) and 25.18 ( P < 0.001), respectively. CONCLUSION: Patients with normal coronary arteries have excellent long-term prognosis, but the risk for MACE increases with non-obstructive and obstructive CAD. Both non-obstructive and obstructive CAD are independently associated with future ischemic events.

Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: ATLANTIC-Morphine.

BACKGROUND: Morphine adversely impacts the action of oral adenosine diphosphate (ADP)-receptor blockers in ST-segment elevation myocardial infarction (STEMI) patients, and is possibly associated with differing patient characteristics. This retrospective analysis investigated whether interaction between morphine use and pre-percutaneous coronary intervention (pre-PCI) ST-segment elevation resolution in STEMI patients in the ATLANTIC study was associated with differences in patient characteristics and management. METHODS: ATLANTIC was an international, multicenter, randomized study of treatment in the acute ambulance/hospital setting where STEMI patients received ticagrelor 180 mg ± morphine. Patient characteristics, cardiovascular history, risk factors, management, and outcomes were recorded. RESULTS: Opioids (97.6% morphine) were used in 921 out of 1862 patients (49.5%). There were no significant differences in age, sex or cardiovascular history, but more morphine-treated patients had anterior myocardial infarction and left-main disease. Time from chest pain to electrocardiogram and ticagrelor loading was shorter with morphine (both p = 0.01) but not total ischemic time. Morphine-treated patients more frequently received glycoprotein IIb/IIIa inhibitors (p = 0.002), thromboaspiration and stent implantation (both p < 0.001). No significant difference between the two groups was found regarding pre-PCI ≥ 70% ST-segment elevation resolution, death, myocardial infarction, stroke, urgent revascularization and definitive acute stent thrombosis. More morphine-treated patients had an absence of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow (85.8% vs. 79.7%; p = 0.001) and more had TIMI major bleeding (1.1% vs. 0.1%; p = 0.02). CONCLUSIONS: Morphine-treatment was associated with increased GP IIb/IIIa inhibitor use, less pre-PCI TIMI 3 flow, and more bleeding. Judicious morphine use is advised with non-opioid analgesics preferred for non-severe acute pain. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.