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1.
Int J Cardiol ; 370: 51-57, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36270493

ABSTRACT

AIMS: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry. METHODS AND RESULTS: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy. CONCLUSIONS: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.' CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov identifier: NCT01991795.


Subject(s)
Coronary Artery Disease , Diabetes Mellitus, Type 2 , Myocardial Infarction , Percutaneous Coronary Intervention , Stroke , Humans , Ticagrelor/therapeutic use , Coronary Artery Disease/drug therapy , Coronary Artery Disease/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Aspirin/therapeutic use , Myocardial Infarction/epidemiology , Stroke/epidemiology , Outcome Assessment, Health Care , Treatment Outcome , Platelet Aggregation Inhibitors/therapeutic use
2.
Eur Heart J Acute Cardiovasc Care ; 11(11): 865-874, 2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36226746

ABSTRACT

Advances in treatment, common cardiovascular (CV) risk factors and the ageing of the population have led to an increasing number of cancer patients presenting with acute CV diseases. These events may be related to cancer itself or cancer treatment. Acute cardiac care specialists must be aware of these acute CV complications and be able to manage them. This may require an individualized and multidisciplinary approach. The management of acute coronary syndromes and acute pericardial diseases in cancer patients was covered in part 1 of a clinical consensus document. This second part focusses on acute heart failure, acute myocardial diseases, venous thromboembolic diseases and acute arrhythmias.


Subject(s)
Acute Coronary Syndrome , Cardiomyopathies , Cardiovascular Diseases , Heart Failure , Neoplasms , Humans , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Risk Factors , Neoplasms/complications , Neoplasms/epidemiology , Neoplasms/therapy , Arrhythmias, Cardiac/therapy , Arrhythmias, Cardiac/complications , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Heart Failure/complications , Heart Failure/therapy , Cardiomyopathies/complications
5.
JACC Basic Transl Sci ; 6(8): 631-646, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34466750

ABSTRACT

The bacterial C-type lectin domain family 4 member E (CLEC4E) has an important role in sterile inflammation, but its role in myocardial repair is unknown. Using complementary approaches in porcine, murine, and human samples, we show that CLEC4E expression levels in the myocardium and in blood correlate with the extent of myocardial injury and left ventricular (LV) functional impairment. CLEC4E expression is markedly increased in the vasculature, cardiac myocytes, and infiltrating leukocytes in the ischemic heart. Loss of Clec4e signaling is associated with reduced acute cardiac injury, neutrophil infiltration, and infarct size. Reduced myocardial injury in Clec4e -/- translates into significantly improved LV structural and functional remodeling at 4 weeks' follow-up. The early transcriptome of LV tissue from Clec4e -/- mice versus wild-type mice reveals significant upregulation of transcripts involved in myocardial metabolism, radical scavenging, angiogenesis, and extracellular matrix organization. Therefore, targeting CLEC4E in the early phase of ischemia-reperfusion injury is a promising therapeutic strategy to modulate myocardial inflammation and enhance repair after ischemia-reperfusion injury.

6.
Eur Heart J Acute Cardiovasc Care ; 10(8): 947-959, 2021 Oct 27.
Article in English | MEDLINE | ID: mdl-34453829

ABSTRACT

Advances in treatment, common cardiovascular (CV) risk factors and the ageing of the population have led to an increasing number of cancer patients presenting with acute CV diseases. These events may be related to the cancer itself or the cancer treatment. Acute cardiac care specialists must be aware of these acute CV complications and be able to manage them. This may require an individualized and multidisciplinary approach. We summarize the most common acute CV complications of cytotoxic, targeted, and immune-based therapies. This is followed by a proposal for a multidisciplinary approach where acute cardiologists work close together with the treating oncologists, haematologists, and radiation specialists, especially in situations where immediate therapeutic decisions are needed. In this first part, we further focus on the management of acute coronary syndromes and acute pericardial diseases in patients with cancer.


Subject(s)
Acute Coronary Syndrome , Cardiovascular Diseases , Neoplasms , Acute Coronary Syndrome/therapy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/therapy , Consensus , Humans , Neoplasms/complications , Neoplasms/therapy , Pericardium
7.
J Am Coll Cardiol ; 78(5): 421-433, 2021 08 03.
Article in English | MEDLINE | ID: mdl-34325831

ABSTRACT

BACKGROUND: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). RESULTS: In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (Pinteraction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. CONCLUSIONS: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Cardiovascular Diseases/prevention & control , Cholesterol, LDL/blood , Lipoprotein(a)/blood , PCSK9 Inhibitors/therapeutic use , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/complications , Aged , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Female , Humans , Male , Middle Aged
8.
Am J Cardiol ; 144 Suppl 1: S23-S31, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33706987

ABSTRACT

Dual antiplatelet therapy (DAPT), the combination of aspirin (ASA), and a P2Y12 inhibitor, protects against stent thrombosis and new atherothrombotic events after a stent implantation or an acute coronary syndrome, but exposes patients to an increased risk of bleeding. In most current practices, the P2Y12 inhibitor is stopped at 6 to 12 months and ASA is continued indefinitely. The advent of safer stents, with less risk of stent thrombosis, has challenged this standard of care, however. A number of alternative strategies involving earlier de-escalation of the antiplatelet therapy have therefore been proposed. In these approaches, standard DAPT is switched to a less potent antithrombotic combination at an earlier time-point than recommended by guidelines. Three different de-escalation variations have been tested to date. The first one maintains DAPT but switches from the potent P2Y12 inhibitors ticagrelor or prasugrel to either a lower dose or to clopidogrel, while maintaining ASA. The 2 other approaches involve changing DAPT to a single antiplatelet at some earlier time-point after the percutaneous coronary intervention procedure, by stopping either the P2Y12 inhibitor or ASA. These strategies have all demonstrated some benefit in clinical trials so far, but especially the contribution of ASA in secondary prevention is clearly evolving as its role in increasing bleeding complications while not providing increased ischemic benefit is becoming more and more clear. In contemporary practice, the type and duration of DAPT should now be based on an individualized decision, and the de-escalation strategies, if used wisely, can be added to the existing options.


Subject(s)
Acute Coronary Syndrome/therapy , Aspirin/administration & dosage , Dual Anti-Platelet Therapy , Graft Occlusion, Vascular/prevention & control , Platelet Aggregation Inhibitors/administration & dosage , Purinergic P2Y Receptor Antagonists/administration & dosage , Drug Administration Schedule , Humans , Percutaneous Coronary Intervention , Stents
9.
Acta Cardiol ; 76(8): 863-869, 2021 Oct.
Article in English | MEDLINE | ID: mdl-32727305

ABSTRACT

AIMS: The current study assessed the impact of COVID-19-related public containment measures (i.e. lockdown) on the ST elevation myocardial infarction (STEMI) epidemic in Belgium. METHODS AND RESULTS: Clinical characteristics, reperfusion therapy modalities, COVID-19 status and in-hospital mortality of consecutive STEMI patients who were admitted to Belgian hospitals for percutaneous coronary intervention (PCI) were recorded during a three-week period starting at the beginning of the lockdown period on 13 March 2020. Similar data were collected for the same time period for 2017-2019. An evaluation of air quality revealed a 32% decrease in ambient NO2 concentrations during lockdown (19.5 µg/m³ versus 13.2 µg/m³, p < .001). During the three-week period, there were 188 STEMI patients admitted for PCI during the lockdown versus an average 254 STEMI patients before the lockdown period (incidence rate ratio = 0.74, p = .001). Reperfusion strategy was predominantly primary PCI in both time periods (96% versus 95%). However, there was a significant delay in treatment during the lockdown period, with more late presentations (>12 h after onset of pain) (14% versus 7.6%, p = .04) and with longer door-to-balloon times (median of 45 versus 39 min, p = .02). Although the in-hospital mortality between the two periods was comparable (5.9% versus 6.7%), 5 of the 7 (71%) COVID-19-positive STEMI patients died. CONCLUSION: The present study revealed a 26% reduction in STEMI admissions and a delay in treatment of STEMI patients. Less exposure to external STEMI triggers (such as ambient air pollution) and/or reluctance to seek medical care are possible explanations of this observation.


Subject(s)
COVID-19 , Communicable Disease Control , Epidemics , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Belgium/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Humans , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/epidemiology
10.
Eur Heart J Qual Care Clin Outcomes ; 7(6): 601-607, 2021 10 28.
Article in English | MEDLINE | ID: mdl-32941605

ABSTRACT

AIMS: To assess the adherence to established quality indicators (QIs) for ST-elevation myocardial infarction (STEMI) at the hospital-network level and its relation to outcome. METHODS AND RESULTS: The data of 7774 STEMI patients admitted to 32 STEMI networks during the period 2014-18 were extracted from the Belgian STEMI database. Five QIs [primary percutaneous coronary intervention use, diagnosis-to-balloon time (DiaTB) <90 min, door-to-balloon time (DoTB) <60 min, P2Y12 inhibitor and statin prescription at discharge, and a composite QI score ranging from 0 to 10] were correlated with in-hospital mortality adjusted for differences in baseline risk profile (TIMI risk score). The median composite QI score was 6.5 [interquartile range (IQR) 6-8]. The most important gaps in quality adherence were related to time delays: the recommended DiaTB and DoTB times across the different networks were achieved in 68% (IQR 53-71) and 67% (IQR 50-78), respectively. Quality adherence was better in networks taking care of more high-risk STEMI patients. The median in-hospital mortality among the STEMI networks was 6.4% (IQR 4.1-7.9%). There was a significant independent inverse correlation between the composite QI score and in-hospital mortality (partial correlation coefficient: -0.45, P = 0.013). Stepwise regression analysis revealed that among the individual QIs, prolonged DiaTB was the most important independent outcome predictor. CONCLUSION: Among established STEMI networks, the time delay between diagnosis and treatment was the most variable and the most relevant prognostic QI, underscoring the importance of assessing quality of care throughout the whole network.


Subject(s)
ST Elevation Myocardial Infarction , Belgium/epidemiology , Hospitals , Humans , Quality Indicators, Health Care , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/therapy , Time Factors
11.
J Cardiovasc Transl Res ; 14(2): 213-221, 2021 04.
Article in English | MEDLINE | ID: mdl-32607873

ABSTRACT

The treatment and early outcome of patients with acute myocardial infarction (MI) have dramatically improved the past decades, but the incidence of left ventricular (LV) dysfunction post-MI remains high. Peripheral blood RNAs reflect pathophysiological changes during acute MI and the inflammatory process. Therefore, these RNAs are promising new markers to molecularly phenotype patients and improve the early identification of patients at risk of subsequent LV dysfunction. We here discuss the coding and long non-coding RNAs that can be measured in peripheral blood of patients with acute MI and list the advantages and limitations for implementation in clinical practice. Although some studies provide preliminary evidence of their diagnostic and prognostic potential, the use of these makers has not yet been implemented in clinical practice. The added value of RNAs to improve treatment and outcome remains to be determined in larger clinical studies. International consortia are now catalyzing renewed efforts to investigate novel RNAs that may improve post-MI outcome in a precision-medicine approach. Graphical Abstract Peripheral blood RNAs reflect the inflammatory changes in acute MI. A number of studies provide preliminary evidence of their prognostic potential, although the use of these makers has not yet been assessed in clinical practice.


Subject(s)
Myocardial Infarction/complications , RNA, Messenger/blood , RNA, Untranslated/blood , Translational Research, Biomedical , Ventricular Dysfunction, Left/etiology , Ventricular Function, Left , Animals , Biomarkers/blood , Clinical Decision-Making , Humans , Inflammation Mediators/blood , Myocardial Infarction/blood , Myocardial Infarction/genetics , Myocardial Infarction/physiopathology , Predictive Value of Tests , Prognosis , RNA, Messenger/genetics , RNA, Untranslated/genetics , Risk Assessment , Risk Factors , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/genetics , Ventricular Dysfunction, Left/physiopathology
12.
Catheter Cardiovasc Interv ; 97(5): E607-E613, 2021 04 01.
Article in English | MEDLINE | ID: mdl-32761890

ABSTRACT

OBJECTIVES: Report the results at 2 years of the patients included in the SENIOR trial. BACKGROUND: Patients above 75 years of age represent a fast-growing population in the cathlab. In the SENIOR trial, patients treated by percutaneous coronary intervention (PCI) with drug eluting stent (DES) and a short duration of P2Y12 inhibitor (1 and 6 months for stable and unstable coronary syndromes, respectively) compared with bare metal stents (BMS) was associated with a 29% reduction in the rate of all-cause mortality, myocardial infarction (MI), stroke, and ischaemia-driven target lesion revascularization (ID-TLR) at 1 year. The results at 2 years are reported here. METHODS AND RESULTS: We randomly assigned 1,200 patients (596[50%] to the DES group and 604[50%] to the BMS group). At 2 years, the composite endpoint of all-cause mortality, MI, stroke and ID-TLR had occurred in 116 (20%) patients in the DES group and 131 (22%) patients in the BMS group (RR 0.90 [95%CI 0.72-1.13], p = .37). IDTLR occurred in 14 (2%) patients in the DES group and 41 (7%) patients in the BMS group (RR 0.35 [95%CI 0.16-0.60], p = .0002). Major bleedings (BARC 3-5) occurred in 27(5%) patients in both groups (RR 1.00, [95%CI 0.58-1.75], p = .99). Stent thrombosis rates were low and similar between DES and BMS (0.8 vs 1.3%, (RR 0.52 [95%CI 0.01-1.95], p = .27). CONCLUSION: Among elderly PCI patients, a strategy combining a DES together with a short duration of DAPT is associated with a reduction in revascularization up to 2 years compared with BMS with very few late events and without any increased in bleeding complications or stent thrombosis.


Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Percutaneous Coronary Intervention , Aged , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Humans , Percutaneous Coronary Intervention/adverse effects , Prosthesis Design , Risk Factors , Stents , Treatment Outcome
13.
Am Heart J ; 226: 140-146, 2020 08.
Article in English | MEDLINE | ID: mdl-32553932

ABSTRACT

BACKGROUND: The STREAM study demonstrated that a pharmaco-invasive strategy was at least as effective as primary PCI (pPCI) in patients presenting early with ST-elevation myocardial infarction (STEMI). The current trial is a response to the finding that reduced intracranial hemorrhage (ICH) in patients ≥75 years occurred after halving the dose of tenecteplase. Additionally, a subsequent analysis of full dose tenecteplase or alteplase in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT) trials demonstrated a steep increase in bleeding events beginning around the age of 60 years. METHODS: STREAM-2 will compare the efficacy and safety of a novel pharmaco-invasive strategy as compared to routine pPCI in STEMI patients ≥60 years presenting within 3 hours from symptom onset. In the pharmaco-invasive arm patients will receive half-dose tenecteplase, as soon as possible before transport to a PCI center. In the pPCI arm, patients will be treated according to optimal standard of care defined by local practice. The key criteria for efficacy will be the number of patients achieving ≥50% ST-segment resolution before and after PCI in lead with maximal ST elevation at baseline and the clinical endpoints of death, congestive heart failure, shock or re-infarction, rescue PCI and aborted myocardial infarction, both singularly and as a composite at 30 days. Key safety criteria are total stroke, ICH and major non-intracranial bleeds. Approximately 600 patients will be randomized (400 to pharmaco-invasive treatment and 200 to pPCI). An interim analysis is planned after 300 patients are enrolled to consider adapting the trial to include a larger sample size aimed at undertaking a formal confirmatory trial. DISCUSSION: The study will provide new insights aimed at establishing an effective and safer pharmaco-invasive treatment for the growing population of older STEMI patients who cannot undergo timely pPCI.


Subject(s)
Fibrinolytic Agents/administration & dosage , Percutaneous Coronary Intervention , Randomized Controlled Trials as Topic/methods , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/surgery , Tenecteplase/administration & dosage , Age Factors , Aged , Humans , Prospective Studies , Time Factors
15.
Eur Heart J Acute Cardiovasc Care ; 9(4_suppl): S153-S160, 2020 Nov.
Article in English | MEDLINE | ID: mdl-31452398

ABSTRACT

AIM: Cardiac arrest is a common complication of ST elevation myocardial infarction and is associated with high mortality. We evaluated whether vulnerability to cardiac arrest follows a circadian rhythm and whether it is related to specific patient characteristics. METHODS: A total of 24,164 ST elevation myocardial infarction patients who were admitted to 60 Belgian hospitals between 2008-2017 were analysed. The proportion of patients with cardiac arrest before initiation of reperfusion therapy was calculated for different time periods (hour of the day, months, seasons) and related to patient characteristics using stepwise logistic regression analysis. RESULTS: Cardiac arrest occurred in 10.8% of the ST elevation myocardial infarction patients at a median of 65 min (interquartile range 33-138 min) after onset of pain. ST elevation myocardial infarction patients with cardiac arrest showed a biphasic pattern with one peak in the morning and one peak in the late afternoon. Multivariate analysis identified the following independent factors associated with cardiac arrest: cardiogenic shock (odds ratio=28), left bundle branch block (odds ratio=3.7), short (<180 min) ischaemic period (odds ratio=2.2), post-meridiem daytime presentation (odds ratio=1.4), anterior infarction (odds ratio=1.3). Overall in-hospital mortality was 30% for cardiac arrest patients versus 3.7% for non-cardiac arrest patients (p<0.0001). CONCLUSION: In the present study population, cardiac arrest in ST elevation myocardial infarction showed an atypical circadian rhythm with not only a morning peak but also a second peak in the late afternoon, suggesting that cardiac arrest and ST elevation myocardial infarction triggers are, at least partially, different. In addition, specific patient characteristics, such as short ischaemic period, cardiogenic shock and left bundle branch block, increase the vulnerability to cardiac arrest.


Subject(s)
Heart Arrest/etiology , Population Surveillance , Registries , ST Elevation Myocardial Infarction/complications , Belgium/epidemiology , Coronary Angiography , Electrocardiography , Female , Follow-Up Studies , Heart Arrest/epidemiology , Hospital Mortality/trends , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/physiopathology , Time Factors
16.
Eur Heart J ; 41(24): 2248-2258, 2020 06 21.
Article in English | MEDLINE | ID: mdl-31732742

ABSTRACT

AIMS: Lowering low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular risk irrespective of age, but the evidence is less strong for older patients. METHODS AND RESULTS: This prespecified analysis from ODYSSEY OUTCOMES compared the effect of alirocumab vs. placebo in 18 924 patients with recent acute coronary syndrome (ACS) according to age. We examined the effect of assigned treatment on occurrence of the primary study outcome, a composite of coronary heart disease death, myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization [major adverse cardiovascular event (MACE)] and all-cause death. Relative risk reductions were consistent for patients ≥65 vs. <65 years for MACE [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.68-0.91 vs. 0.89, 0.80-1.00; Pinteraction = 0.19] and all-cause death [HR 0.77, 0.62-0.95 vs. 0.94, 0.77-1.15; Pinteraction = 0.46], and consistent for MACE when dichotomizing at age 75 years (HR 0.85, 0.64-1.13 in ≥75 vs. 0.85, 0.78-0.93 in <75, Pinteraction = 0.19). When considering age as a continuous variable in regression models, advancing age increased risk of MACE, as well as the absolute reduction in MACE with alirocumab, with numbers-needed-to-treat for MACE at 3 years of 43 (25-186) at age 45 years, 26 (15-97) at age 75 years, and 12 (6-81) for those at age 85 years. Although adverse events were more frequent in older patients, there were no differences between alirocumab and placebo. CONCLUSION: In patients with recent ACS, alirocumab improves outcomes irrespective of age. Increasing absolute benefit but not harm with advancing age suggests that LDL-C lowering is an important preventive intervention for older patients after ACS.


Subject(s)
Acute Coronary Syndrome , Brain Ischemia , Stroke , Acute Coronary Syndrome/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Humans , Middle Aged , Treatment Outcome
17.
Value Health ; 22(12): 1355-1361, 2019 12.
Article in English | MEDLINE | ID: mdl-31806191

ABSTRACT

BACKGROUND: Elderly patients receive bare metal stents instead of drug-eluting stents (DES) to shorten the duration of dual antiplatelet therapy (DAPT). The SENIOR trial compared outcomes between these 2 types of stents combined with a short duration of DAPT. A significant decrease in the number of patients with at least 1 major adverse cardiac and cerebrovascular event (MACCE) was noted in the DES group. OBJECTIVES: The objective of this article was to perform an economic evaluation of the SENIOR trial. METHODS: This evaluation was performed separately in 5 participating countries using pooled patient-level data from all study patients and country-specific unit costs and utility values. Costs, MACCEs, and quality-adjusted life-years (QALYs) were calculated in both arms at 1 year, and an incremental cost-effectiveness ratio was estimated. Uncertainty was explored by probabilistic bootstrapping. RESULTS: A total of 1200 patients underwent randomization. The average total cost per patient was higher in the DES group. The number of MACCEs and average QALYs were not statistically different between the 2 groups. The 1-year incremental cost-effectiveness ratio for each country of reference ranged from €13 752 to €20 511/MACCE avoided and from €42 835 to €68 231/QALY gained. The scatter plots found a wide dispersion, reflecting a large uncertainty surrounding the results. But in each country studied, 90% of the bootstrap replications indicated a higher cost for greater effectiveness for the DES group. Assuming a willingness to pay of €50 000/QALY, there was between a 40% and 50% chance that the use of DES was cost-effective in 4 countries. CONCLUSION: The use of DES instead of bare metal stents combined with a short duration of DAPT in elderly patients induced higher cost for greater effectiveness in each of the 5 countries studied.


Subject(s)
Coronary Artery Disease/therapy , Drug-Eluting Stents/economics , Aged , Analysis of Variance , Benchmarking , Coronary Artery Disease/economics , Cost-Benefit Analysis , Europe , Humans , Quality-Adjusted Life Years , Single-Blind Method , Treatment Outcome
18.
Circ Genom Precis Med ; 12(12): e002656, 2019 12.
Article in English | MEDLINE | ID: mdl-31756302

ABSTRACT

BACKGROUND: The identification of patients with acute myocardial infarction (MI) at risk of subsequent left ventricular (LV) dysfunction remains challenging, but it is important to optimize therapies. The aim of this study was to determine the unbiased RNA profile in peripheral blood of patients with acute MI and to identify and validate new prognostic markers of LV dysfunction. METHODS: We prospectively enrolled a discovery cohort with acute MI (n=143) and performed whole-blood RNA profiling at different time points. We then selected transcripts on admission that related to LV dysfunction at follow-up and validated them by quantitative polymerase chain reaction in the discovery cohort, in an external validation cohort (n=449), and in a representative porcine MI model with cardiac magnetic resonance-based measurements of infarct size and postmortem myocardial pathology (n=33). RESULTS: RNA profiling in the discovery cohort showed upregulation of genes involved in chemotaxis, IL (interleukin)-6, and NF-κB (nuclear factor-κB) signaling in the acute phase of MI. Expression levels of the majority of these transcripts paralleled the rise in cardiac troponin T and decayed at 30 days. RNA levels of QSOX1, PLBD1, and S100A8 on admission with MI correlated with LV dysfunction at follow-up. Using quantitative polymerase chain reaction, we confirmed that QSOX1 and PLBD1 predicted LV dysfunction (odds ratio, 2.6 [95% CI, 1.1-6.1] and 3.2 [95% CI, 1.4-7.4]), whereas S100A8 did not. In the external validation cohort, we confirmed QSOX1 and PLBD1 as new independent markers of LV dysfunction (odds ratio, 1.41 [95% CI, 1.06-1.88] and 1.43 [95% CI, 1.08-1.89]). QSOX1 had an incremental predictive value in a model consisting of clinical variables and cardiac biomarkers (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]). In the porcine MI model, whole-blood levels of QSOX1 and PLBD1 related to neutrophil infiltration in the ischemic myocardium in an infarct size-independent manner. CONCLUSIONS: Peripheral blood QSOX1 and PLBD1 in acute MI are new independent markers of LV dysfunction post-MI.


Subject(s)
Lysophospholipase/genetics , Myocardial Infarction/complications , Oxidoreductases Acting on Sulfur Group Donors/genetics , RNA/blood , Ventricular Dysfunction, Left/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Cohort Studies , Female , Humans , Longitudinal Studies , Lysophospholipase/blood , Male , Middle Aged , Myocardial Infarction/blood , Oxidoreductases Acting on Sulfur Group Donors/blood , Prospective Studies , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/etiology
19.
Acta Cardiol ; 74(1): 60-64, 2019 Feb.
Article in English | MEDLINE | ID: mdl-29560788

ABSTRACT

BACKGROUND: The optimal therapeutic strategy for ST-segment elevation myocardial infarction (STEMI) patients found to have multi-vessel disease (MVD) is controversial but recent data support complete revascularisation (CR). Whether CR should be completed during the index admission or during a second staged admission remains unclear. Our main objective was to measure rates of major adverse cardiovascular events (MACEs) during the waiting period in STEMI patients selected for staged revascularisation (SR), in order to determine the safety of delaying CR. For completeness, we also describe 30-day and long-term outcomes in STEMI patients with MVD who underwent in-hospital CR. METHODS: A single-centre retrospective analysis of 931 STEMI patients treated by primary percutaneous coronary intervention (PCI) identified 397 patients with MVD who were haemodynamically stable and presented within 12 hours of chest pain onset. Of these, 191 underwent multi-vessel PCI: 49 during the index admission and 142 patients undergoing a strategy of SR. RESULTS: Our main finding was that waiting period MACE were 2% (three of 142) in patients allocated to SR (at a median of 31 days). In patients allocated to in-hospital CR, 30-day MACE rates were 10% (five of 49). During a median follow up of 39 months, all-cause mortality was 7.0% vs. 28.6%, and cardiac mortality was 2% vs. 8%, in patients allocated to SR or CR, respectively. CONCLUSIONS: Patients with STEMI and MVD who, based on clinical judgement, were allocated to a second admission SR strategy had very few adverse events during the waiting period and excellent long-term outcomes.


Subject(s)
Inpatients , Registries , ST Elevation Myocardial Infarction/surgery , Belgium/epidemiology , Cause of Death/trends , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Male , Middle Aged , Preoperative Period , Retrospective Studies , Risk Factors , ST Elevation Myocardial Infarction/diagnosis , Survival Rate/trends , Time Factors
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