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BACKGROUND: Patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) or Takotsubo syndrome (TS) often suffer from poor mental health and low quality-of-life post event, with no current evidence-based treatments available. This study aimed to evaluate the effects of an internet-delivered cognitive behavioral therapy program on stress and anxiety symptoms in patients diagnosed with myocardial infarction with nonobstructive coronary arteries or TS.

METHODS: A parallel, multicenter, randomized controlled trial with a wait-list control group was conducted. Patients with elevated symptoms of stress or anxiety were included (the 14-item perceived stress scale ≥25 or hospital anxiety and depression scale, anxiety subscale ≥8). The primary outcome was normalized stress and anxiety levels 10 to 12 weeks after randomization. Secondary outcomes included normalized stress and anxiety separately and symptoms as continuous measures.

RESULTS: A total of 88 patients were randomized (treatment: 45, control: 43). The treatment group showed a greater, though not statistically significant proportion of normalized patients (odds ratio, 2.37 [95% CI, 0.88–6.38], P=0.09). Secondary analyses indicated treatment effects on anxiety normalization and on symptoms as continuous measures (effect sizes: d=0.44–0.67). There was also an interaction between treatment and diagnosis (TS versus non-TS), favoring a treatment effect in TS patients (P=0.016).

CONCLUSIONS: The patient-tailored internet-delivered cognitive behavioral therapy program reduced stress and anxiety symptoms in patients with myocardial infarction with nonobstructive coronary arteries or TS and normalized anxiety symptoms in a greater proportion of treated patients than controls. Exploratory analyses indicated that patients with TS may experience greater benefit from the internet-delivered cognitive behavioral therapy intervention, but this warrants further research.

Aims: Myocardial infarction with non-obstructive coronary arteries (MINOCA) and takotsubo syndrome (TS) are both characterized by lack of significant coronary artery stenoses and a higher prevalence of mental health disorders preceding the event. Currently, little is known about their pathological aetiologies and subsequent treatment plans, giving cause for concern among those affected. The objective of this review is to provide a comprehensive overview of mental health status and quality of life (QoL) in MINOCA and TS patients after the acute event, compared with both cardiac and non-cardiac populations, and over time.

Methods and results: A systematic search was conducted via Cochrane Library, CINAHL, PsycINFO, PubMed, ASSIA, Web of Science, Scopus, and Embase from inception to May 2024. The review was registered in PROSPERO and methods, and results were reported in accordance with the PRISMA guidelines. Quality assessment and risk of bias were evaluated using the Newcastle-Ottawa Scale for cross-sectional and cohort studies. Sample sizes ranged from 13 to 5322 participants. The risk of bias was high in 18/28, medium in 7/28, and low in 3/28 studies. Across the symptoms assessed, MINOCA and TS patients reported worse mental health status or QoL than non-cardiac groups in 10/13 studies and cardiac groups in 10/20 studies. Investigating change over time, 1/5 studies found deteriorating mental health status, 3/5 reported improved mental health status or QoL, and 1/5 reported no change in MINOCA and TS patients.

Conclusion: Patients with MINOCA or TS seem to have worse mental health status and QoL after the acute event than non-cardiac individuals, but it is yet difficult to conclude whether mental distress and QoL are equal or worse compared with coronary heart disease patients. There is no convincing evidence that mental health status or QoL of MINOCA and TS patients naturally improve over time after the acute event. Among the studies evaluated, risk of bias was high. More high-quality studies are needed, investigating mental health status and QoL among MINOCA and TS patients. This is a systematic review of all papers reporting data on post-event mental health status and quality of life in individuals following either a MINOCA or takotsubo syndrome. Individuals who have suffered a MINOCA or takotsubo syndrome more often report worse mental health status and quality of life than healthy controls and at least as often or more often than other cardiac patients. Much of the available data had a high risk of bias, demonstrating a lack of high-quality investigation of the mental well-being of these patients, and more attention is warranted.

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.

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.

Background: Acute coronary syndrome (ACS) encompasses acute myocardial infarction (AMI) and unstable angina (UA). It is a global major cause of morbidity and mortality in both the short and long terms. The risk for recurrent ischemic cardiovascular (CV) events and death after ACS depends on patient factors at presentation, revascularization and secondary prevention measures. Of these, ischemic stroke (IS) is a feared and potentially devastating complication that confers suffering for the individual patient and an economic burden on society. ACS and secondary prevention treatment have gone through dramatic improvements during recent decades. These improvements, together with an improved risk factor profile in the general population, have led to lower morbidity and halved mortality. ACS and IS share many risk factors. Most of our knowledge about prognosis and risk of recurrent ischemic events after ACS is based on clinical trials and it is uncertain whether these findings can be translated to the general population. 

Aims: The study aims were as follows: to estimate the rate, time trends, risk factors and effects on mortality of IS after an AMI during the decades that ACS and secondary prevention treatment improved; to study wether the switch from the antiplatelet agent clopidogrel to ticagrelor influenced post-AMI IS risk in patients treated with PCI, based on data from the SWEDEHEART register; and to estimate the long-term rate of subsequent CV events after ACS in an unselected cohort of ACS patients, based on the ACS-population in the Nurse-based Age- independent Intervention to Limit Evolution of Disease After Acute Coronary Syndrome (NAILED-ACS) study. 

Methods: In papers I–IV, data from the SWEDEHEART register were merged with the Swedish National Patient Register (NPR) to identify patients with AMI and subsequent ischemic stroke. In paper V, data were obtained from the NAILED-ACS study. Survival analysis with Kaplan–Meier estimates and hazard ratios for risk factors with Cox proportional hazards regression models were calculated in all five studies. When appropriate, propensity scores and competing risk analyses were used to adjust for baseline differences and a high overall mortality rate, respectively. 

Results: The overall IS rates at 30 days and 1 year after AMI were 2.1 and 4.1% respectively, during the study period (1998–2008). The rate of IS after AMI decreased over time, both at 30 days and at 1 year, with relative risk reductions (RRRs) of 11% at 30 days and 20% at 1 iii year respectively, when comparing the beginning and end of the study period. 

AMI complicated by IS within 1 year had a higher mortality rate than AMI without IS (36.5 vs. 18.3%). The mortality rates decreased during 1998– 2008, by 9.4% in patients with IS and 7.5% in those without IS.

The introduction of dual antiplatelet therapy (DAPT) with ticagrelor instead of clopidogrel was associated with a 21% relative risk reduction of IS within 1 year after AMI in patients treated with PCI. 

The rate of recurrent CV events (CV death, AMI and IS) after ACS during the first year was 10.3% and remained high during a median follow-up time of 4.7 years, at 28.6%.

Predictors of increased risk of recurrent ischemic events were older age, female sex, previously established CV and cerebrovascular disease, hypertension, atrial fibrillation, diabetes mellitus, heart failure and renal disease. Reperfusion and revascularization procedures in the acute phase as well as evidence-based secondary prevention treatment were associated with a protective effect against recurrent ischemic events. 

Conclusion: The results reported in this thesis indicate an overall high rate of recurrent CV events after ACS based on a contemporary, unselected population of ACS patients. IS a relatively rare, but serious complication after AMI that confers a substantially increased mortality risk. The rate and mortality risk of IS after AMI have decreased over time. Improved, evidence-based treatment, both in the acute phase and in the long term, has most likely reduced the post-ACS risk of recurrent ischemic events in general and more specifically of IS. The switch from clopidogrel to ticagrelor was associated with a small, but statistically significant reduction in IS risk in PCI-treated AMI patients. 

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.

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.

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.

ObjectivesTo 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).MethodsData 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.ResultsOf 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.ConclusionsThe 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.

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.