Bivalirudin versus heparin in ST and non-ST-segment elevation myocardial infarction-Outcomes at two years.

BACKGROUND: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years. METHODS: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here. RESULTS: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups. CONCLUSIONS: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02311231.

Long-term risk of major adverse cardiovascular events following ischemic stroke or TIA.

Data are scarce on long-term outcomes after ischemic stroke (IS) or transient ischemic attack (TIA). In this prospective cohort study, we examined the cumulative incidence of major adverse cardiovascular events (MACE) after IS and TIA using a competing risk model and factors associated with new events using a Cox-proportional hazard regression model. All patients discharged alive from Östersund Hospital with IS or TIA between 2010 and 2013 (n = 1535) were followed until 31 December 2017. The primary endpoint was a composite of IS, type 1 acute myocardial infarction (AMI), and cardiovascular (CV) death. Secondary endpoints were the individual components of the primary endpoint, in all patients and separated in IS and TIA subgroups. The cumulative incidence of MACE (median follow-up: 4.4 years) was 12.8% (95% CI: 11.2-14.6) within 1 year after discharge and 35.6% (95% CI: 31.8-39.4) by the end of follow-up. The risk of MACE and CV death was significantly increased in IS compared to TIA (p-values < 0.05), but not the risk of IS or type 1 AMI. Age, kidney failure, prior IS, prior AMI, congestive heart failure, atrial fibrillation, and impaired functional status, were associated with an increased risk of MACE. The risk of recurring events after IS and TIA is high. IS patients have a higher risk of MACE and CV death than TIA patients.

Incidence and predictors of cardiovascular outcomes after acute coronary syndrome in a population-based cohort study.

There is limited data on long-term outcomes after hospitalization for ACS. We aimed to estimate the rate of recurrent cardiovascular events in the long-term, in a population-based, unselected cohort of ACS patients. We included 1379 patients with ACS hospitalized at Östersund hospital 2010-2014 and followed them from the day after discharge to 31 December 2017. The primary endpoint was the unadjusted rate of the composite of CV death, AMI and ischemic stroke. Risk factors for the primary endpoint were assessed in a multivariable Cox proportional hazards regression model. During a median follow-up of 4.7 years, the unadjusted rate of the primary endpoint was 10.3% at 1 year and 28.6% at the end of follow-up. Predictors of increased risk for subsequent events were congestive heart failure, diabetes mellitus, angina pectoris, prior revascularization with PCI or CABG and treatment with diuretics at discharge. Lipid-lowering therapy at discharge and revascularization with PCI or CABG were associated with a lower risk of recurrent events. The risk of recurrent cardiovascular was high at 1 year and continued to be so during the following almost 3 years of median follow-up. Established predictors of cardiovascular risk were confirmed.

Transradial versus trans-femoral access site in high-speed rotational atherectomy in Sweden.

BACKGROUND: Radial artery is the preferred access site in contemporary percutaneous coronary intervention (PCI). However, limited data exist regarding utilization pattern, safety, and long-term efficacy of transradial artery access (TRA) PCI in heavily calcified lesions using high-speed rotational atherectomy (HSRA). METHODS: All patients who underwent HSRA-PCI in Sweden between 2005 and 2016 were included. Outcomes were major adverse cardiac events (MACE, including death, myocardial infarction (MI) or target vessel revascularisation (TVR)), in-hospital bleeding and restenosis. Inverse probability of treatment weighting was used to adjust for the non-randomized access site selection. RESULTS: We included 1479 patients of whom 649 had TRA and 782 transfemoral artery access (TFA) HSRA-PCI. The rate of TRA increased significantly by 18% per year but remained lower in HSRA-PCI (60%) than in the overall PCI population (85%) in 2016. TRA was associated with comparable angiographic success but significantly lower risk for major (adjusted OR 0.16; 95% CI 0.05-0.47) or any in-hospital bleeding (adjusted OR 0.32; 95% CI 0.13-0.78). At one year, the adjusted risk for MACE (HR 0.87; 95% CI 0.67-1.13) and its individual components did not differ between TRA and TFA patients. The risk for restenosis did not significantly differ between TRA and TFA HSRA-PCI treated lesions (adjusted HR 0.92; 95% CI 0.46-1.81). CONCLUSION: HSRA-PCI by TRA was associated with significantly lower risk for in-hospital bleeding and equivalent long-term efficacy when compared with TFA. Our data support the feasibility and superior safety profile of TRA in HSRA-PCI.

Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y12-inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry). METHODS: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days. RESULTS: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y12-inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P=0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P=0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P=0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P=0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P=0.04). CONCLUSIONS: In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y12-inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

Incidence and predictors of serious bleeding during long-term follow-up after acute coronary syndrome in a population-based cohort study.

Progress in decreasing ischemic complications in acute coronary syndrome (ACS) has come at the expense of increased bleeding risk. We estimated the long-term, post-discharge incidence of serious bleeding, characterized bleeding type, and identified predictors of bleeding and its impact on mortality in an unselected cohort of patients with ACS. In this population-based study, we included 1379 patients identified with an ACS, 2010-2014. Serious bleeding was defined as intracranial hemorrhage (ICH), bleeding requiring hospital admission, or bleeding requiring transfusion or surgery. During a median 4.6-year follow-up, 85 patients had ≥ 1 serious bleed (cumulative incidence, 8.6%; 95% confidence interval (CI) 8.3-8.9). A subgroup of 557 patients, aged ≥ 75 years had a higher incidence (13.4%) than younger patients (6.0%). The most common bleeding site was gastrointestinal (51%), followed by ICH (27%). Sixteen percent had a recurrence. Risk factors for serious bleeding were age ≥ 75 years, lower baseline hemoglobin (Hb) value, previous hypertension or heart failure. Serious bleeding was associated with increased mortality. Bleeding after ACS was fairly frequent and the most common bleeding site was gastrointestinal. Older age, lower baseline Hb value, hypertension and heart failure predicted bleeding. Bleeding did independently predict mortality.

Nurse-based secondary preventive follow-up by telephone reduced recurrence of cardiovascular events: a randomised controlled trial.

Enhanced follow-up is needed to improve the results of secondary preventive care in patients with established cardiovascular disease. We examined the effect of long-term, nurse-based, secondary preventive follow-up by telephone on the recurrence of cardiovascular events. Open, randomised, controlled trial with two parallel groups. Between 1 January 2010 and 31 December 2014, consecutive patients (n = 1890) admitted to hospital due to stroke, transient ischaemic attack (TIA), or acute coronary syndrome (ACS) were included. Participants were randomised (1:1) to nurse-based telephone follow-up (intervention, n = 944) or usual care (control, n = 946) and followed until 31 December 2017. The primary endpoint was a composite of stroke, myocardial infarction, cardiac revascularisation, and cardiovascular death. The individual components of the primary endpoint, TIA, and all-cause mortality were analysed as secondary endpoints. The assessment of outcome events was blinded to study group assignment. After a mean follow-up of 4.5 years, 22.7% (n = 214) of patients in the intervention group and 27.1% (n = 256) in the control group reached the primary composite endpoint (HR 0.81, 95% CI 0.68-0.97; ARR 4.4%, 95% CI 0.5-8.3). Secondary endpoints did not differ significantly between groups. Nurse-based secondary preventive follow-up by telephone reduced the recurrence of cardiovascular events during long-term follow-up.

Long-term mortality in patients with ischaemic heart failure revascularized with coronary artery bypass grafting or percutaneous coronary intervention: insights from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

AIMS: To compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for treatment of patients with heart failure due to ischaemic heart disease. METHODS AND RESULTS: We analysed all-cause mortality following CABG or PCI in patients with heart failure with reduced ejection fraction and multivessel disease (coronary artery stenosis >50% in ≥2 vessels or left main) who underwent coronary angiography between 2000 and 2018 in Sweden. We used a propensity score-adjusted logistic and Cox proportional-hazards regressions and instrumental variable model to adjust for known and unknown confounders. Multilevel modelling was used to adjust for the clustering of observations in a hierarchical database. In total, 2509 patients (82.9% men) were included; 35.8% had diabetes and 34.7% had a previous myocardial infarction. The mean age was 68.1 ± 9.4 years (47.8% were >70 years old), and 64.9% had three-vessel or left main disease. Primary designated therapy was PCI in 56.2% and CABG in 43.8%. Median follow-up time was 3.9 years (range 1 day to 10 years). There were 1010 deaths. Risk of death was lower after CABG than after PCI [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.41-0.96; P = 0.031]. The risk of death increased linearly with quintiles of hospitals in which PCI was the preferred method for revascularization (OR 1.27, 95% CI 1.17-1.38, Ptrend < 0.001). CONCLUSION: In patients with ischaemic heart failure, long-term survival was greater after CABG than after PCI.

Radial artery access is associated with lower mortality in patients undergoing primary PCI: a report from the SWEDEHEART registry.

OBJECTIVES: The purpose of this observational study was to evaluate the effects of radial artery access versus femoral artery access on the risk of 30-day mortality, inhospital bleeding and cardiogenic shock in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: We used data from the SWEDEHEART registry and included all patients who were treated with primary percutaneous coronary intervention in Sweden between 2005 and 2016. We compared patients who had percutaneous coronary intervention by radial access versus femoral access with regard to the primary endpoint of all-cause death within 30 days, using a multilevel propensity score adjusted logistic regression which included hospital as a random effect. RESULTS: During the study period, 44,804 patients underwent primary percutaneous coronary intervention of whom 24,299 (54.2%) had radial access and 20,505 (45.8%) femoral access. There were 2487 (5.5%) deaths within 30 days, of which 920 (3.8%) occurred in the radial access and 1567 (7.6%) in the femoral access group. After propensity score adjustment, radial access was associated with a lower risk of death (adjusted odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55-0.88, P = 0.025). We found no interaction between access site and age, gender and cardiogenic shock regarding 30-day mortality. Radial access was also associated with a lower adjusted risk of bleeding (adjusted OR 0.45, 95% CI 0.25-0.79, P = 0.006) and cardiogenic shock (adjusted OR 0.41, 95% CI 0.24-0.73, P = 0.002). CONCLUSIONS: In patients with ST-elevation myocardial infarction, primary percutaneous coronary intervention by radial access rather than femoral access was associated with an adjusted lower risk of death, bleeding and cardiogenic shock. Our findings are consistent with, and add external validity to, recent randomised trials.

Association of Pretreatment With P2Y12 Receptor Antagonists Preceding Percutaneous Coronary Intervention in Non-ST-Segment Elevation Acute Coronary Syndromes With Outcomes.

Importance: Pretreatment of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with P2Y12 receptor antagonists is a common practice despite the lack of definite evidence for its benefit. Objective: To investigate the association of P2Y12 receptor antagonist pretreatment vs no pretreatment with mortality, stent thrombosis, and in-hospital bleeding in patients with NSTE-ACS undergoing percutaneous coronary intervention (PCI). Design, Setting, and Participants: This cohort study used prospective data from the Swedish Coronary Angiography and Angioplasty Registry of 64 857 patients who underwent procedures between 2010 and 2018. All patients who underwent PCI owing to NSTE-ACS in Sweden were stratified by whether they were pretreated with P2Y12 receptor antagonists. Associations of pretreatment with P2Y12 receptor antagonists with the risks of adverse outcomes were investigated using instrumental variable analysis and propensity score matching. Data were analyzed from March to June 2019. Exposures: Pretreatment with P2Y12 receptor antagonists. Main Outcomes and Measures: The primary end point was all-cause mortality within 30 days. Secondary end points were 1-year mortality, stent thrombosis within 30 days, and in-hospital bleeding. Results: In total, 64 857 patients (mean [SD] age, 64.7 [10.9] years; 46 809 [72.2%] men) were included. A total of 59 894 patients (92.4%) were pretreated with a P2Y12 receptor antagonist, including 27 867 (43.7%) pretreated with clopidogrel, 34 785 (54.5%) pretreated with ticagrelor, and 1148 (1.8%) pretreated with prasugrel. At 30 days, there were 971 deaths (1.5%) and 101 definite stent thromboses (0.2%) in the full cohort. Pretreatment was not associated with better survival at 30 days (odds ratio [OR], 1.17; 95% CI, 0.66-2.11; P = .58), survival at 1 year (OR, 1.34; 95% CI, 0.77-2.34; P = .30), or decreased stent thrombosis (OR, 0.81; 95% CI, 0.42-1.55; P = .52). However, pretreatment was associated with increased risk of in-hospital bleeding (OR, 1.49; 95% CI, 1.06-2.12; P = .02). Conclusions and Relevance: This cohort study found that pretreatment of patients with NSTE-ACS with P2Y12 receptor antagonists was not associated with improved clinical outcomes but was associated with increased risk of bleeding. These findings support the argument that pretreatment with P2Y12 receptor antagonists should not be routinely used in patients with NSTE-ACS.

Incidence and outcome of myocardial infarction treated with percutaneous coronary intervention during COVID-19 pandemic.

OBJECTIVE: Most reports on the declining incidence of myocardial infarction (MI) during the COVID-19 have either been anecdotal, survey results or geographically limited to areas with lockdowns. We examined the incidence of MI during the COVID-19 pandemic in Sweden, which has remained an open society with a different public health approach fighting COVID-19. METHODS: We assessed the incidence rate (IR) as well as the incidence rate ratios (IRRs) of all MI referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR), during the COVID-19 pandemic in Sweden (1 March 2020-7 May 2020) in relation to the same days 2015-2019. RESULTS: A total of 2443 MIs were referred for coronary angiography during the COVID-19 pandemic resulting in an IR 36 MIs/day (204 MIs/100 000 per year) compared with 15 213 MIs during the reference period with an IR of 45 MIs/day (254 MIs/100 000 per year) resulting in IRR of 0.80, 95% CI (0.74 to 0.86), p<0.001. Results were consistent in all investigated patient subgroups, indicating no change in patient category seeking cardiac care. Kaplan-Meier event rates for 7-day case fatality were 439 (2.3%) compared with 37 (2.9%) (HR: 0.81, 95% CI (0.58 to 1.13), p=0.21). Time to percutaneous coronary intervention (PCI) was shorter during the pandemic and PCI was equally performed, indicating no change in quality of care during the pandemic. CONCLUSION: The COVID-19 pandemic has significantly reduced the incidence of MI referred for invasive treatment strategy. No differences in overall short-term case fatality or quality of care indicators were observed.

Radial versus femoral access in patients with acute coronary syndrome undergoing invasive management: A prespecified subgroup analysis from VALIDATE-SWEDEHEART.

AIMS: In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with acute coronary syndrome undergoing invasive management. We assessed whether the access site had an impact on the primary endpoint of death, myocardial infarction or major bleeding at 180 days and whether it interacted with bivalirudin/unfractionated heparin. METHODS AND RESULTS: A total of 6006 patients with acute coronary syndrome planned for percutaneous coronary intervention were randomised to either bivalirudin or unfractionated heparin. Arterial access was left to the operator discretion. Overall, 90.5% of patients underwent transradial access and 9.5% transfemoral access. Baseline risk was higher in transfemoral access. The unadjusted hazard ratio for the primary outcome was lower with transradial access (hazard ratio 0.53, 95% confidence interval 0.43-0.67, p<0.001) and remained lower after multivariable adjustment (hazard ratio 0.56, 95% confidence interval 0.52-0.84, p<0.001). Transradial access was associated with lower risk of death (hazard ratio 0.41, 95% confidence interval 0.28-0.60, p<0.001) and major bleeding (hazard ratio 0.57, 95% confidence interval 0.44-0.75, p<0.001). There was no interaction between treatment with bivalirudin and access site for the primary endpoint (p=0.976) or major bleeding (p=0.801). CONCLUSIONS: Transradial access was associated with lower risk of death, myocardial infarction or major bleeding at 180 days. Bivalirudin was not associated with less bleeding, irrespective of access site.

Increase in ticagrelor use over time is associated with lower rates of ischemic stroke following myocardial infarction.

OBJECTIVES: To evaluate the impact of a rapid change in preferred treatment from clopidogrel to ticagrelor on the risk of ischemic stroke following acute myocardial infarction (AMI). METHODS: Data for AMI patients treated with either clopidogrel or ticagrelor were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). Patients were divided into two cohorts, each covering a two-year time period; the initial prescription of ticagrelor (20 Dec 2011) was used as a cut-off point. Patients in the early cohort (n = 23,447) were treated with clopidogrel, while those in the later cohort (n = 24,227), were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). Kaplan-Meier analyses were used to assess the risk of ischemic stroke over time, with multivariable Cox regression analyses used to identify predictors of ischemic stroke. RESULTS: Of 47,674 patients, there were 1203 cases of ischemic stroke. Cumulative Kaplan-Meier incidence estimates of ischemic stroke after one year were 2.8% vs. 2.4% for the early and late cohorts, respectively (p = 0.001). Older age, hypertension, diabetes, previous stroke, congestive heart failure, atrial fibrillation, and ST-elevation myocardial infarction were associated with an increased risk of ischemic stroke. Percutaneous coronary intervention and statins at discharge were associated with a decreased risk of ischemic stroke, as was higher estimated glomerular filtration rate. Membership of the late cohort correlated with a 13% reduction in the relative risk of ischemic stroke. CONCLUSIONS: The introduction of ticagrelor as well as an improved management of AMI was associated with a lower rate of ischemic stroke in a relatively unselected AMI population.

Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial infarction.

BACKGROUND: The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use. METHODS: In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days. RESULTS: A total of 3001 patients with non-ST-elevation myocardial infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503) and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups, respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95% confidence interval 0.78-1.18, p=0.69). The results were consistent in all major subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68-1.94, p=0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58-1.45, p=0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77-1.24, p=0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33, 0.30-5.93, p=0.82). CONCLUSION: Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

Ischemic stroke rates decrease with increased ticagrelor use after acute myocardial infarction in patients treated with percutaneous coronary intervention.

Aims It is unknown whether dual antiplatelet therapy with ticagrelor instead of clopidogrel reduces the risk of ischaemic stroke in acute myocardial infarction patients that undergo percutaneous coronary intervention. This study investigated whether the introduction of dual antiplatelet therapy with ticagrelor was associated with reduced ischaemic stroke risk in a real-world population. Methods and results Patients with ischaemic stroke after acute myocardial infarction from 8 December 2009-31 December 2013 were identified using the Register for Information and Knowledge on Swedish Heart Intensive Care Admissions and the Swedish National Patient Register. The study period was divided into two similar periods using the date of the first prescription of ticagrelor as the cut-off. The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients during the first period (100% clopidogrel treatment) versus the second period (60.7% ticagrelor treatment) was assessed using Kaplan-Meier analysis. Variables associated with ischaemic stroke were identified using a multivariable Cox proportional hazards model. There were 686 ischaemic stroke events (2.0%) among 34931 percutaneous coronary intervention-treated acute myocardial infarction patients within one year, 366 (2.2%) during the first period and 320 (1.8%) during the second period ( p = 0.004). The Cox model showed a 21% relative risk reduction in ischaemic stroke in the second period versus the first one (hazard ratio 0.79, 95% confidence interval, 0.68-0.92; p = 0.003). The independent predictors of increased stroke risk were older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and ST-segment elevation myocardial infarction. Conclusion The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients decreased after the introduction of ticagrelor in Sweden.

Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

BACKGROUND: The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS: In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS: A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). CONCLUSIONS: Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).

Incidence, trends, and predictors of ischemic stroke 1 year after an acute myocardial infarction.

BACKGROUND AND PURPOSE: Ischemic stroke after acute myocardial infarction is an important complication. It is unknown whether the risk has changed because the treatment of acute myocardial infarction has improved during the past decade. There is also conflicting data about predictors of stroke risk. METHODS: To obtain the 1-year incidence of stroke after acute myocardial infarction, the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions database for the years 1998 to 2008 was merged with the Swedish National Patient Register (NPR). The time trend was studied by dividing the entire time period into 5 separate periods. Independent predictors were identified using a multivariable Cox proportional hazards regression model. RESULTS: Between 1998 and 2008, 7185 of 173 233 patients with acute myocardial infarction had an ischemic stroke within 1 year (4.1%). There was a 20% relative risk reduction during the study period (1998-2000 versus 2007-2008) relative risk 0.80 (95% confidence interval, 0.75-0.86; P<0.001. Independent predictors of stroke were age, female sex, ST-segment-elevation myocardial infarction, previous stroke, previous diabetes mellitus, heart failure at admission, angiotensin-converting enzyme inhibitor treatment and atrial fibrillation. Reperfusion treatment with fibrinolysis and percutaneous coronary intervention and treatment with aspirin, P2Y12-inhibitors, and statins predicted a reduced risk of stroke. CONCLUSIONS: The risk of ischemic stroke within a year after myocardial infarction is substantial but has clearly been reduced during the studied time period. The major predictive factors found to correlate well with previous investigations. Reperfusion treatment, thrombocyte aggregation inhibition, and lipid lowering are the main contributors to the observed risk reduction.

The Nurse-Based Age Independent Intervention to Limit Evolution of Disease After Acute Coronary Syndrome (NAILED ACS) Risk Factor Trial: Protocol for a Randomized Controlled Trial.

BACKGROUND: Secondary prevention after acute coronary syndrome (ACS) is essential to reduce morbidity and mortality, but related studies have been fairly small or performed as clinical trials with non-representative patient selection. Long-term follow-up data are also minimal. A nurse-led follow-up for risk factor improvement may be effective, but the evidence is limited. OBJECTIVE: The aims of this study are to perform an adequately sized, nurse-led, long-term secondary preventive follow-up with inclusion of an unselected population of ACS patients. The focus will be on lipid and blood pressure control as well as tobacco use and physical activity. METHODS: The study will consist of a randomized, controlled, long-term, population-based trial with two parallel groups. Patients will be included during the initial hospital stay. Important outcome variables are total cholesterol, low-density lipoprotein (LDL) cholesterol, and sitting systolic and diastolic blood pressure. Outcomes will be measured after 12, 24, and 36 months of follow-up. Trained nurses will manage the intervention group with the aim of achieving set treatment goals as soon as possible. The control group will receive usual care. At least 250 patients will be included in each group to reliably detect a difference in mean LDL of 0.5 mmol/L and in mean systolic blood pressure of 5 mmHg. RESULTS: The study is ongoing and recruitment of participants will continue until December 31, 2014. CONCLUSIONS: This study will test the hypothesis that a nurse-led, long-term follow-up after an ACS with a focus on achieving treatment goals as soon as possible is an effective secondary preventive method. If proven effective, this method could be implemented in general practice at a low cost. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 96595458; http://www.controlled-trials.com/ISRCTN96595458 (Archived by WebCite at http://www.webcitation.org/6RlyhYTYK).

Incidence, trends, and predictors of ischemic stroke 30 days after an acute myocardial infarction.

BACKGROUND AND PURPOSE: Ischemic stroke is a known complication of acute myocardial infarction (AMI). Treatment of AMI has undergone great changes in recent years. We aimed to investigate whether changes in treatment corresponded to a lower incidence of ischemic stroke and which factors predicted ischemic stroke after AMI. METHODS: Data were taken from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions. Patients with their first registered AMI between 1998 and 2008 were included. To identify ischemic strokes, we used the Swedish national patient register. To study a potential trend in the incidence of ischemic stroke after AMI over time, we divided the patient population into 5 time periods. Event-free survival was studied by Kaplan-Meier analysis. Cox proportional hazards regression model was used to identify stroke predictors. RESULTS: Of 173,233 patients with AMI, 3571 (2.1%) developed ischemic stroke within 30 days. The incidence of ischemic stroke was significantly lower during the years 2007 to 2008 compared with 1998 to 2000, with respective rates of 2.0% and 2.2% (P=0.02). Independent predictors of an increased risk of stroke were age, female sex, prior stroke, diabetes mellitus, atrial fibrillation, clinical signs of heart failure in hospital, ST-segment-elevation myocardial infarction, coronary artery bypass grafting, and angiotensin-converting enzyme inhibitor treatment at discharge. Percutaneous coronary intervention, fibrinolysis, acetylsalicylic acid, statins, and P2Y12 inhibitors were predictors of reduced risk of stroke. CONCLUSIONS: The incidence of ischemic stroke within 30 days of an AMI has decreased during the period 1998 to 2008. This decrease is associated with increased use of acetylsalicylic acid, P2Y12 inhibitors, statins, and percutaneous coronary intervention.

Mortality after ischemic stroke in patients with acute myocardial infarction: predictors and trends over time in Sweden.

BACKGROUND AND PURPOSE: Acute myocardial infarction (AMI) increases the risk of ischemic stroke, and mortality among these patients is high. Here, we aimed to estimate the 1-year mortality reliably after AMI complicated by ischemic stroke. We also aimed to identify trends over time for mortality during 1998-2008, as well as factors that predicted increased or decreased mortality. METHODS: Data for 173 233 unselected patients with AMI were collected from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions registry for 1998-2008. Specifically, we analyzed 1-year follow-up and mortality data for patients with AMI with and without ischemic stroke. Kaplan-Meyer analysis was used to analyze mortality trends over time, and Cox regression analysis was used to identify uni- and multivariate predictors of mortality. RESULTS: The 1-year mortality was 36.5% for AMI complicated by ischemic stroke and 18.3% for AMI without stroke. Mortality decreased over time in patients with and without ischemic stroke. The absolute decreases in mortality were 9.4% and 7.5%, respectively. Reperfusion and secondary preventive therapies were associated with a decreased mortality rate. CONCLUSIONS: Mortality after AMI complicated by an ischemic stroke is very high but decreased from 1998 to 2008. The increased use of evidence-based therapies explains the improved prognosis.