| 1. |
- Patel, Riyaz S., et al.
(författare)
-
Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
-
Ingår i: Circulation. - 2574-8300. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
|
|
| 2. |
- Patel, Riyaz S., et al.
(författare)
-
Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
-
Ingår i: Circulation. - 2574-8300. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
|
|
| 3. |
- Voight, Benjamin F, et al.
(författare)
-
Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study
- 2012
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9841, s. 572-580
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
|
|
| 4. |
- Bueno, Hector, et al.
(författare)
-
Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome : Executive summary
- 2019
-
Ingår i: European Heart Journal. - : SAGE PUBLICATIONS LTD. - 2048-8726 .- 2048-8734. ; 8:8, s. 745-754
-
Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) should be studied separately for therapies aimed at the specific pathophysiology of either condition, particularly for treatment of the acute phase, but can be studied together for other treatments, especially long-term therapy. Unstable angina patients should be excluded from acute phase ACS trials. In general, cardiovascular death and reinfarction are recommended for primary efficacy endpoints; other endpoints may be considered if specifically relevant for the therapy under study. New agents or interventions should be tested against a background of evidence-based therapy with expanded follow-up for safety assessment. In conclusion, new guidance documents for randomized controlled trials in ACS should consider changes regarding patient and endpoint selection and definitions, and trial designs. Specific requirements for the evaluation of novel pharmacological therapies need further clarification.
|
|
| 5. |
- Tubaro, Marco, et al.
(författare)
-
Pre-Hospital Treatment of STEMI Patients : A Scientific Statement of the Working Group Acute Cardiac Care of the European Society of Cardiology
- 2012
-
Ingår i: Revista Española de Cardiología. - : Elsevier BV. - 0300-8932 .- 1579-2242. ; 65:1, s. 60-70
-
Tidskriftsartikel (refereegranskat)abstract
- In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the eff ectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.
|
|
| 6. |
|
|
| 7. |
- Patrono, Carlo, et al.
(författare)
-
Antiplatelet agents for the treatment and prevention of atherothrombosis
- 2011
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 32:23, s. 2922-32
-
Forskningsöversikt (refereegranskat)abstract
- The clinical pharmacology of antiplatelet drugs has been reviewed previously by the European Society of Cardiology (ESC) Task force and by the 8th American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. Moreover, information on the efficacy and safety of antiplatelet drugs in the treatment and prevention of atherothrombosis is provided by collaborative meta-analyses of 287 secondary prevention trials and 6 primary prevention trials. The present document intends to provide practicing physicians with an updated instrument to guide their choice of the most suitable antiplatelet strategy for the individual patient at risk, or with different clinical manifestations, of atherothrombosis.
|
|
| 8. |
- van Diepen, Sean, et al.
(författare)
-
Efficacy and Safety of Vorapaxar in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Undergoing Noncardiac Surgery
- 2015
-
Ingår i: Journal of the American Heart Association. - 2047-9980. ; 4:12
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Perioperative antiplatelet agents potentially increase bleeding after non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). The protease-activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy and safety in noncardiac surgery (NCS) remain unknown. We aimed to evaluate ischemic, bleeding, and long-term outcomes of vorapaxar in NCS after NSTE ACS.METHODS AND RESULTS: In the TRACER trial, 2202 (17.0%) patients underwent major or minor NCS after NSTE ACS over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular death, myocardial infarction, stent thrombosis, or urgent revascularization within 30 days of NCS. Safety outcomes included 30-day NCS bleeding and GUSTO moderate/severe bleeding. Overall, 1171 vorapaxar and 1031 placebo patients underwent NCS. Preoperative aspirin and thienopyridine use was 96.8% versus 97.7% (P=0.235) and 89.1% versus 86.1% (P=0.036) for vorapaxar versus placebo, respectively. Within 30 days of NCS, no differences were observed in the primary ischemic end point between vorapaxar and placebo groups (3.4% versus 3.9%; adjusted odds ratio 0.81, 95% CI 0.50 to 1.33, P=0.41). Similarly, no differences in NCS bleeding (3.9% versus 3.4%; adjusted odds ratio 1.41, 95% CI 0.87 to 2.31, P=0.17) or GUSTO moderate/severe bleeding (4.2% versus 3.7%; adjusted odds ratio 1.15, 95% CI, 0.72 to 1.83, P=0.55) were observed. In a 30-day landmarked analysis, NCS patients had a higher long-term risk of the ischemic end point (adjusted hazard ratio 1.62, 95% CI 1.33 to 1.97, P<0.001) and GUSTO moderate/severe bleeding (adjusted hazard ratio 5.63, 95% CI 3.98 to 7.97, P<0.001) versus patients who did not undergo NCS, independent of study treatment.CONCLUSION: NCS after NSTE ACS is common and associated with more ischemic outcomes and bleeding. Vorapaxar after NSTE ACS was not associated with increased perioperative ischemic or bleeding events in patients undergoing NCS.
|
|
| 9. |
- Al-Faleh, Hussam, et al.
(författare)
-
Unraveling the spectrum of left bundle branch block in acute myocardial infarction : insights from the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT 2 and 3) trials
- 2006
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 151:1, s. 10-5
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Left bundle branch block (LBBB) complicates the diagnosis of acute myocardial infarction (AMI). The Sgarbossa criteria were developed from GUSTO I to surmount this diagnostic challenge but have not been prospectively validated in a large population with presumed AMI. We evaluated their utility in the diagnosis and risk stratification of AMI patients in ASSENT 2 & 3. METHODS: Baseline electrocardiograms (ECG) of LBBB patients were scored using Sgarbossa's criteria (0-10) by 2 readers blinded to the CK/CK-MB data and clinical outcomes; 267 (1.2%) patients had LBBB on their baseline ECG. RESULTS: Among 253 LBBB patients with available peak CK/CK-MB data, 158 (62.5%) had peak CK/CK-MB levels > 2x ULN, thereby qualifying for the diagnosis of AMI. A Sgarbossa score of 3 was shown in 48.7% of LBBB patients with elevated CK/CK-MB versus in 12.6% of those without a CK/CK-MB rise (P < .001). Patients with higher Sgarbossa scores, ie, 3, had a higher mortality compared with those with a score < 3, (23.5% vs 7.7% at 30 days P < .001; and 33.7% vs 20.2% at 1 year, P < .001, respectively). CONCLUSIONS: Our findings validate the utility of Sgarbossa criteria for diagnosing AMI in the setting of LBBB. These criteria provide a simple and practical diagnostic approach to risk stratify this diagnostically challenging high-risk group and optimize risk-benefit of acute therapy.
|
|
| 10. |
- Alfredsson, Joakim, et al.
(författare)
-
Sex differences in management and outcomes of patients with type 2 diabetes and cardiovascular disease: A report from TECOS
- 2018
-
Ingår i: Diabetes, obesity and metabolism. - : WILEY. - 1462-8902 .- 1463-1326. ; 20:10, s. 2379-2388
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine sex differences in baseline characteristics and outcomes in patients with type 2 diabetes and atherosclerotic vascular disease. Materials and methods: Cox models were used to analyse the association between sex and outcomes in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), a randomized, placebo-controlled trial assessing the impact of sitagliptin on cardiovascular (CV) outcomes in patients with type 2 diabetes and atherosclerotic vascular disease. Results: A total of 4297 women and 10 374 men were followed for a median of 3.0 years. Women were slightly older and more often had cerebrovascular disease and peripheral arterial disease but less often coronary heart disease than men. At baseline, women were less likely to use aspirin or statins. The primary composite outcome of CV death, myocardial infarction, stroke, or hospitalization for unstable angina occurred in 418 women (9.7%) and 1272 men (12.3%; 3.48 vs 4.38 events/100 participant-years, crude hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.71-0.89, adjusted HR 0.64, 95% CI 0.55-0.74; P amp;lt; .0001). Women also had a significantly lower risk of secondary CV outcomes and all-cause death. Conclusions: In this large prospective study of people with type 2 diabetes and CV disease, women had different CV disease burden, worse CV risk factor profiles, and less use of indicated medications than men. Despite this, women had significantly lower risk of CV events, suggesting that the cardioprotective effects of female sex extend to populations with type 2 diabetes.
|
|
| 11. |
|
|
| 12. |
- Armaganijan, Luciana V., et al.
(författare)
-
Effect of age on efficacy and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome : Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial
- 2016
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 178, s. 176-184
-
Tidskriftsartikel (refereegranskat)abstract
- Background Antithrombotic therapy plays an important role in the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. Methods Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. Results The median age of the population was 64 years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were <= 54 years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75 years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (>= 75 years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (<= 54 years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively (P value for interaction = .574). Conclusion Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.
|
|
| 13. |
- Armstrong, Paul W., et al.
(författare)
-
Efficacy and safety of unfractionated heparin versus enoxaparin : a pooled analysis of ASSENT-3 and -3 PLUS data
- 2006
-
Ingår i: CMJA. Canadian Medical Association Journal. Onlineutg. Med tittel. - : CMA Joule Inc.. - 0820-3946 .- 1488-2329. ; 174:10, s. 1421-1426
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The optimal antithrombotic therapy to accompany tenecteplase in cases of acute ST-segment elevation myocardial infarction (STEMI) remains unclear. We undertook a prespecified pooled analysis of data from the ASSENT-3 and ASSENT-3 PLUS trials. METHODS: We created a combined database of the 2040 and 818 patients who received enoxaparin in ASSENT-3 and ASSENT-3 PLUS, respectively, and compared them with the 2038 and 821 patients who received unfractionated heparin. RESULTS: The efficacy end point (a composite of 30-day mortality, reinfarction or refractory ischemia) was 12.2% with enoxaparin versus 16.0% with unfractionated heparin (p < 0.001); the combined end point of efficacy plus safety (a composite of 30-day mortality, reinfarction, refractory ischemia, intracranial hemorrhage [ICH] or major systemic bleeding) was 15.0% versus 18.0%, respectively (p = 0.003) [corrected] The 1049 patients urgently revascularized had greater benefit from enoxaparin (15.4% v. 10.1%, p = 0.013), yet the excess in major systemic bleeding evident with enoxaparin (3.3% v. 2.4%, p = 0.01) was largely confined to the 3492 patients without or before revascularization. Although ICH rates in the groups were similar (1.3% v. 0.9%, p = 0.26), an excess of ICH occurred among those administered enoxaparin during the ASSENT-3 PLUS trial (6.7% v. 0.8%, p = 0.013), especially among women over 75 years of age. INTERPRETATION: These data demonstrated the benefit of enoxaparin used in conjunction with tenecteplase, but raised caution about its prehospital use to treat STEMI in elderly women.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Bagai, Akshay, et al.
(författare)
-
Magnitude of troponin elevation and long-term clinical outcomes in acute coronary syndrome patients treated with and without revascularization.
- 2015
-
Ingår i: Circulation. Cardiovascular Interventions. - 1941-7640 .- 1941-7632. ; 8:6
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In patients with non-ST-segment-elevation acute coronary syndrome (NSTE ACS), elevated troponin levels identify patients at high risk for adverse outcomes; however, it is unknown whether the magnitude of troponin elevation during hospitalization remains predictive of subsequent events in patients undergoing coronary revascularization.METHODS AND RESULTS: We studied 12 635 patients with NSTE ACS in the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) study with at least 1 troponin measurement during index hospitalization. Cox proportional hazards regression was used to examine the relationship between peak troponin level (standardized as the ratio of peak troponin value measured during hospitalization and local laboratory upper reference limit [URL]) and revascularization on all-cause mortality at 2 years. Revascularization (percutaneous coronary intervention or coronary artery bypass graft) was performed during index hospitalization in 8586 patients (68.0%); revascularized patients had higher peak troponin ratios (median, 23 versus 9.5× URL). Among patients that did not undergo revascularization, the mortality rate at 2 years increased in a curvilinear fashion with increasing levels of peak troponin. In contrast, the mortality rate at 2 years remained constant irrespective of peak troponin levels among revascularized patients (P for interaction=0.004). This relationship was unchanged after multivariable adjustment.CONCLUSIONS: There is a differential relationship between the magnitude of troponin elevation and long-term mortality in ACS patients treated with and without revascularization. Although prognostically important in patients treated without revascularization, the prognostic implications of peak troponin level seem to be minimal in revascularized patients.
|
|
| 17. |
- Björklund, Erik, et al.
(författare)
-
Outcome of ST-elevation myocardial infarction treated with thrombolysis in the unselected population is vastly different from samples of eligible patients in a large-scale clinical trial
- 2004
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 148:4, s. 566-573
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Patients in clinical trials of fibrinolytic agents have been shown to be younger, less often female, and to have lower risk characteristics and a better outcome compared with unselected patients with ST-elevation myocardial infarction. However, a direct comparison of patients treated with fibrinolytic agents and not enrolled versus those enrolled in a trial, including a large number of patients, has not been performed.METHODS:Prospective data from the Swedish Register of Cardiac Intensive Care on patients admitted with acute myocardial infarction treated with thrombolytic agents in 60 Swedish hospitals were linked to data on trial participants in the ASsessment of Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial of fibrinolytic agents. Baseline characteristics, treatments, and long-term outcome were evaluated in 729 trial participants (A2), 2048 nonparticipants at trial hospitals (non-A2), and 964 nonparticipants at other hospitals (non-A2-Hosp).RESULTS:Nontrial patients compared with A2 patients were older and had higher risk characteristics and more early complications, although the treatments were similar. Patients at highest risk of death were the least likely to be enrolled in the trial. The 1-year mortality rate was 8.8% versus 20.3% and 19.0% (P <.001 for both) among A2 compared with non-A2 and non-A2-Hosp patients, respectively. After adjustment for a number of risk factors, the 1-year mortality rate was still twice as high in nontrial compared with A2 patients.CONCLUSIONS:The adjusted 1-year mortality rate was twice as high in patients treated with fibrinolytic agents and not enrolled in a clinical trial compared with those enrolled. One major reason for the difference in outcome appeared to be the selection of less critically ill patients to the trial.
|
|
| 18. |
- Bugiardini, Raffaele, et al.
(författare)
-
Angina, "normal" coronary angiography, and vascular dysfunction : risk assessment strategies
- 2007
-
Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 4:2, s. e12-
-
Tidskriftsartikel (refereegranskat)abstract
- Chest pain may be associated with coronary arteries that appear "normal". Normal is defined here as no visible disease or luminal irregularities (less than 50%) as judged visually at coronary angiography. Normal angiography in patients with chest pain is five times more common in women than in men [1]. Among patients with chest pain and normal angiography, an unknown number are suffering from cardiac pain of ischemic origin. Uncertainty is often difficult to allay, for medical attendants as well as for patients, resulting in perpetuation of symptoms, difficulties in management, and establishment of risk of subsequent coronary events [2]. In this article, we discuss how to stratify risk in patients with chest pain and a normal coronary angiogram.
|
|
| 19. |
|
|
| 20. |
- Chang, Wei-Ching, et al.
(författare)
-
Forecasting mortality : dynamic assessment of risk in ST-segment elevation acute myocardial infarction
- 2006
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:4, s. 419-426
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: To demonstrate the feasibility and clinical utility of developing dynamic risk assessment models for ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: In 6066 STEMI patients enrolled in the Assessment of the Safety and Efficacy of a New Thrombolytic-3 (ASSENT-3) trial with complete electrocardiographic data, we assessed the probability of 30-day mortality over the following forecasting periods beginning at day 0 (baseline), 3 h, day 2, and day 5 using multiple-logistic regression. These models were validated and simplified in independent samples of 1622 similar fibrinolytic-treated patients from the ASSENT-3 PLUS trial and in 814 STEMI patients undergoing primary percutaneous coronary intervention in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial. The discriminatory power of these predictive models, from baseline to day 5, was excellent (c-statistics 0.80 to 0.87); and their predictive ability was supported by strong gradients in mortality outcomes as the risk score increased. Dynamic modelling also provided information on the change in prognosis over time which may be used to advise more appropriate therapeutic decisions, e.g. the identification of high-risk patients for possible co-interventions. CONCLUSION: Dynamic modelling for STEMI patients enhances the risk assessment and stratification and should provide valuable ongoing guidance for their management.
|
|
| 21. |
- Cornel, Jan H., et al.
(författare)
-
Glycoprotein IIb/IIIa Receptor Inhibitors in Combination With Vorapaxar, a Platelet Thrombin Receptor Antagonist, Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes (from the TRACER Trial)
- 2015
-
Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 115:10, s. 1325-1332
-
Tidskriftsartikel (refereegranskat)abstract
- We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIn/IIIa group; adjusted FIR 1.34, 95% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.
|
|
| 22. |
|
|
| 23. |
- Dellborg, Mikael, 1954, et al.
(författare)
-
Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54.
- 2019
-
Ingår i: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6845 .- 2055-6837. ; 5:4, s. 200-206
-
Tidskriftsartikel (refereegranskat)abstract
- In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60mg b.i.d. initiated up to 2years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.Of the 21162 patients enrolled in PEGASUS-TIMI 54, 10779 patients were included in the primary analysis for this study, randomized to ticagrelor 60mg (n=5388) or matching placebo (n=5391). The cumulative proportions of patients with events at 36months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P=0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P=0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P<0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P=0.58).In PEGASUS-TIMI 54, treatment with ticagrelor 60mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60mg in this population.http://www.clinicaltrials.gov NCT01225562.
|
|
| 24. |
- Déry, Jean-Pierre, et al.
(författare)
-
Arterial access site and outcomes in patients undergoing percutaneous coronary intervention with and without vorapaxar
- 2016
-
Ingår i: Catheterization and cardiovascular interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 88:2, s. 163-173
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We evaluated outcomes associated with transradial vs. transfemoral approaches and vorapaxar in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in the TRACER trial.BACKGROUND: Vorapaxar reduces ischemic events but increases the risk of major bleeding.METHODS: We compared 30-day and 2-year major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization) and noncoronary artery bypass graft (CABG)-related bleedings in 2,192 transradial and 4,880 transfemoral patients undergoing PCI after adjusting for confounding variables, including propensity for transradial access.RESULTS: Overall, 30-day GUSTO moderate/severe and non-CABG TIMI major/minor bleeding occurred less frequently in transradial (0.9% vs. 2.0%, P = 0.001) vs. transfemoral (1.1% vs. 2.5%, P = 0.005) patients. A similar reduction was seen at 2 years (3.3% vs. 4.7%, P = 0.008; 3.3% vs. 4.9%, P < 0.001, respectively). Transradial was associated with an increased risk of ischemic events at 30 days (OR 1.38, 95% CI 1.11-1.72; P = 0.004), driven primarily by increased periprocedural myocardial infarctions. At 2 years, rates of MACE were comparable (HR 1.14, 95% CI 0.98-1.33; P = 0.096). Although bleeding rates were higher with vorapaxar in transfemoral vs. transradial patients, there was no significant treatment interaction. Also, the access site did not modulate the association between vorapaxar and MACE.CONCLUSIONS: Transradial access was associated with lower bleeding rates and similar long-term ischemic outcomes, suggesting transradial access is safer than transfemoral access among ACS patients receiving potent antiplatelet therapies. Because of the nonrandomized allocation of arterial access, these results should be considered exploratory. © 2015 Wiley Periodicals, Inc.
|
|
| 25. |
|
|
