Intensive early and sustained lowering of non-high-density lipoprotein cholesterol after myocardial infarction and prognosis: the SWEDEHEART registry.

BACKGROUND AND AIMS: Non-high-density lipoprotein cholesterol (HDL-C) provides an estimate of lipid-associated risk and is a secondary treatment target after myocardial infarction (MI). The aim was to study the relationship between non-HDL-C levels after MI and risk of adverse outcomes. METHODS: From the SWEDEHEART registry, 56,262 patients with MI were included. Outcomes were major adverse cardiovascular event (MACE: death, MI, ischaemic stroke), death, and non-fatal MI. Non-HDL-C was assessed at admission, 2 months, and 1 year. Target achievement (<2.2 mmol/L) of non-HDL-C, timing thereof, and outcomes were assessed. RESULTS: During median follow-up of 5.4 years, 9549 had MACE, 5427 died, and 3946 had MI. Long-term hazard ratio (HR) for MACE in the lowest versus the highest quartile of achieved non-HDL-C at 1 year was 0.76 (95% confidence interval 0.71-0.81). Short-term results were consistent also when assessing non-HDL-C levels at 2 months, including early events up to 1 year (HR 0.80, 95% CI 0.68-0.92). Similar results were observed for all outcomes. Patients achieving both early and sustained targets had lowest risk of outcomes (HR 0.80 95% CI 0.74-0.86) versus patients achieving target early or late (HR for both 0.86, 95% CI 0.79-0.93). CONCLUSIONS: The lowest achieved levels both at 2 months and at 1 year of non-HDL-C were associated with better outcome. The lowest risk was observed when target was achieved within 2 months of MI and sustained thereafter. These findings challenge the current stepwise approach for cholesterol lowering after MI which inevitably results in delaying goal attainment and possible harm.

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.

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.

Major bleeding in patients with atrial fibrillation treated with apixaban versus warfarin in combination with amiodarone: nationwide cohort study.

BACKGROUND: Amiodarone is an established treatment for atrial fibrillation (AF) but might interfere with the metabolism of apixaban or warfarin. Therefore, the aim was to investigate the occurrence of major bleeding among patients with AF treated with amiodarone in combination with apixaban or warfarin. METHODS: Retrospective observational study using Swedish health registers. All patients with AF in the National Patient Register and the National Dispensed Drug Register with concomitant use of amiodarone and warfarin or apixaban between 1 June 2013 and 31 December 2018 were included. Propensity score matching was performed, and matched cohorts were compared using Cox proportional HRs. The primary outcome was major bleeding resulting in hospitalisation based on International Classification of Diseases (ICD)-10 codes. Secondary outcomes included intracranial bleeding, gastrointestinal bleeding and other bleeding. Exploratory outcomes included ischaemic stroke/systemic embolism and all-cause/cardiovascular (CV) mortality. RESULTS: A total of 12 103 patients met the inclusion criteria and 8686 patients were included after propensity score matching. Rates of major bleeding were similar in the apixaban (4.3/100 patient-years) and warfarin cohort (4.5/100 patient-years) (HR: 1.03; 95% CI: 0.76 to 1.39) during median follow-up of 4.4 months. Similar findings were observed for secondary outcomes including gastrointestinal bleeding and other bleeding, and exploratory outcomes including ischaemic stroke/systemic embolism and all-cause/CV mortality. CONCLUSIONS: Among patients treated with amiodarone in combination with apixaban or warfarin, major bleeding and thromboembolic events were rare and with no significant difference between the treatment groups. EUPAS REGISTRY NUMBER: EUPAS43681.

Metabolic Syndrome Traits Increase the Risk of Major Adverse Liver Outcomes in Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes (T2D) increases the risk for major adverse liver outcomes (MALOs), including cirrhosis and its complications. Patients with T2D frequently have other traits of the metabolic syndrome (MetS). It remains uncertain whether there is a synergistic effect of accumulating MetS traits on future MALO risk. RESEARCH DESIGN AND METHODS: Patients with T2D without a history of liver disease were identified from national registers in Sweden from 1998 to 2021. MetS traits included hypertension, low HDL level, hypertriglyceridemia, obesity, and albuminuria, in addition to T2D. MALO events were identified based on administrative coding from national registers until 31 October 2022. Data were analyzed using Cox regression models. RESULTS: In total, 230,992 patients were identified (median age 64 years; 58% male), of whom 3,215 (1.39%) developed MALOs over a median follow-up of 9.9 years. Compared with patients with one MetS trait (only T2D) at baseline, those with more than one MetS trait had a higher rate of MALOs (adjusted hazard ratio [aHR] 2.33, 95% CI 1.53-3.54). The rate of MALOs increased progressively with increasing numbers of MetS traits at baseline (aHR 1.28 per added trait, 95% CI 1.23-1.33). During follow-up, patients who acquired additional MetS traits had a progressively higher rate of MALOs. The MetS trait with the largest association with incident MALOs was hypertension (aHR 2.06, 95% CI 1.57-2.71). CONCLUSIONS: Having or acquiring additional traits of MetS increase the rate of progression to MALOs in patients with T2D. These results could be used to inform screening initiatives for liver disease.

Randomised, siteless study to compare systematic atrial fibrillation screening using enrichment by a risk prediction model with standard care in a Swedish population aged ≥ 65 years: CONSIDERING-AF study design.

INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and confers an increased risk of mortality, stroke, heart failure and cognitive decline. There is growing interest in AF screening; however, the most suitable population and device for AF detection remains to be elucidated. Here, we present the design of the CONSIDERING-AF (deteCtiON and Stroke preventIon by moDEl scRreenING for Atrial Fibrillation) study. METHODS AND ANALYSIS: CONSIDERING-AF is a randomised, controlled, siteless, non-blinded diagnostic superiority trial with four parallel groups and a primary endpoint of identifying AF during a 6-month study period set in Region Halland, Sweden. In each group, 740 individuals aged≥65 years will be included. The primary objective is to compare the intervention of AF screening enrichment using a risk prediction model (RPM), followed by 14 days of a continuous ECG patch, with no intervention (standard care). Primary outcome is defined as the incident AF recorded in the Region Halland Information Database after 6 months as compared with standard care. Secondary endpoints include the difference in incident AF between groups enriched or not by the RPM, with and without an invitation to 14 days of continuous ECG recording, and the proportions of oral anticoagulation treatment in the four groups. ETHICS AND DISSEMINATION: This study has ethical approval from the Swedish Ethical Review Authority. Results will be published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: NCT05838781.

Oral anticoagulant treatment after bioprosthetic valvular intervention or valvuloplasty in patients with atrial fibrillation-A SWEDEHEART study.

AIMS: To describe the prevalence of atrial fibrillation (AF), use of oral anticoagulants (OAC) and change in antithrombotic treatment patterns during follow-up after valve intervention with a biological prosthesis or valvuloplasty. METHODS AND RESULTS: All patients with history of AF or new-onset AF discharged alive after valvular intervention (biological prosthesis or valvuloplasty) between 2010-2016 in Sweden were included (n = 7,362). Information about comorbidities was collected from national patient registers. Exposure to OAC was based on pharmacy dispensation data. In total 4,800 (65.2%) patients had a history of AF, and 2,562 (34.8%) patients developed new-onset AF, with 999 (39.0%) developing new-onset AF within 3 months after intervention. The proportion of patients with biological valve prosthesis was higher in patients with new-onset AF compared to history of AF (p<0.001). CHA2DS2-VASc score ≥2 was observed in 83.1% and 75.5% patients with history of AF and new-onset AF, respectively. Warfarin was more frequently dispensed than NOAC at discharge in patients with history of AF (43.9% vs 7.3%), and in patients with new-onset AF (36.6% vs 17.1%). Almost half of the AF population was not dispensed on any OAC at discharge (48.8% in patients with history of AF and 46.3% in patients with new-onset AF). CONCLUSION: In this real world study of patients with AF and recent valvular intervention, risk of new-onset AF after valvular intervention is high emphasizing need for frequent rhythm monitoring after intervention. A considerable undertreatment with OAC was observed despite being indicated for the majority of the patients. Warfarin was the OAC most frequently dispensed.

Oral anticoagulants, time in therapeutic range and renal function over time in real-life patients with atrial fibrillation and chronic kidney disease.

AIMS: To describe the use of warfarin and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD), to evaluate changes in renal function over time and predictors of rapid decline, and to describe time in therapeutic range (TTR) and predictors of poor TTR among patients on warfarin. METHODS AND RESULTS: Using data from AuriculA, the Swedish oral anticoagulation registry, patients with AF on warfarin or DOAC were identified between 2013 and 2018 (N=6567). Estimated glomerular filtration rate (eGFR) was calculated and categorised into normal (≥90 mL/min/1.73 m2), mild CKD (60-89 mL/min/1.73 m2), moderate CKD (30-59 mL/min/1.73 m2), severe CKD (15-29 mL/min/1.73 m2) and end-stage CKD (<15 mL/min/1.73 m2)/dialysis. TTR was estimated using international normalised ratio (INR) measurements. Predictors of eGFR decline over time and of poor TTR were estimated using regression analysis. Between 2013 and 2018, use of DOAC increased from 9.2% to 89.3%, with a corresponding decline in warfarin. A similar trend was observed in patients with mild to moderate CKD, while DOAC over warfarin increased slower among patients with severe to end-stage CKD/dialysis. In patients treated with warfarin, the median TTR was 77.1%. Worse TTR was observed among patients with severe CKD (70.0%) and end-stage CKD/dialysis (67.5%). A gradual annual decline in eGFR was observed (-1.1 mL/min/1.73 m2), with a more rapid decline among patients with older age, female sex, diabetes mellitus and/or heart failure. CONCLUSION: In patients with AF, use of DOAC has steadily increased across different CKD stages, but not in patients with severe to end-stage CKD/dialysis despite these patients having poor INR control. Patients with AF have a gradual decline in renal function, with a more rapid decline among a subgroup of patients.

Association of level of kidney function and platelet aggregation in acute myocardial infarction.

BACKGROUND: Decreased kidney function has been established as an important risk factor in patients presenting with acute coronary syndrome. In acute coronary syndrome, increased platelet aggregation is associated with vascular complications. The aim of this study is to examine whether decreased kidney function is associated with altered platelet function in patients presenting with acute myocardial infarction. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 413 patients presenting with acute myocardial infarction admitted to the cardiac intensive care unit at Ostersund Hospital, Ostersund, Sweden. PREDICTORS: Glomerular filtration rate less than 60 mL/min/1.73 m(2) estimated from serum cystatin C level, comorbidity, medications, and markers of inflammation and hemostasis. OUTCOMES & MEASUREMENTS: Platelet aggregation was assessed by measuring the formation of small platelet aggregates (SPAs) by using a laser light scattering method. A greater SPA level indicates greater platelet aggregation. Platelet aggregation analysis was performed on days 1, 2, 3, and 5 in-hospital. RESULTS: We observed a significant increase in platelet aggregation during the first 3 days in the hospital regardless of kidney function (P < 0.001). Platelet aggregation was more pronounced in patients with estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) on day 2 (SPA count, 65,000 versus 47,000; P = 0.01) and day 3 (SPA count, 77,000 versus 52,000; P = 0.02). In a multiple linear regression analysis, decreased kidney function was no longer significantly associated with increased platelet aggregation. Older age, greater plasma fibrinogen level, and diabetes mellitus were associated with increased platelet aggregation in the multivariable model. LIMITATIONS: During the study period, 78 patients presenting with acute myocardial infarction were not eligible for inclusion. Differences in treatment with antiplatelet medication between the 2 groups might have affected our findings. CONCLUSIONS: Platelet aggregation increases during the first days after acute myocardial infarction regardless of kidney function. There is no difference in platelet aggregation in patients according to level of kidney function.

The impact of platelet function or C-reactive protein, on cardiovascular events after an acute myocardial infarction.

BACKGROUND: Recurrent cardiovascular events following acute myocardial infarction (AMI) are common. The purpose of this study was to evaluate the impact of platelet aggregation, PFA-100 closure times and peak C-reactive protein (CRP), respectively, on the occurrence of death, myocardial infarction and ischemic cerebral events after an AMI. Furthermore, to examine the relationship between the platelet function tests and peak CRP. METHODS: Three hundred and thirty-four patients with AMI were included in the study. Platelet aggregation was analyzed by an aggregometer using laser light (PA-200). The state of high residual platelet reactivity was defined as normal closure times (PFA-100) during treatment with aspirin. RESULTS: The fourth quartile of peak CRP was associated with poorer outcome as compared to the first quartile in a multivariate Cox-regression analysis, with a hazard ratio of 2.0 (95% CI 1.1-3.7) for the occurrence of death, myocardial infarction and ischemic cerebral events. The fourth quartile of peak CRP (>64.6 mg/l) was associated with platelet aggregation (p < 0.001, adjusted R2 = 0.13) and high residual platelet reactivity, in a multivariate model, with an odds ratio of 2.9 (CI 95% 1.3-6.8), as compared to the first quartile. Neither the highest quartile of platelet aggregation nor the state of high residual platelet reactivity predicted new cardiovascular events. CONCLUSION: In patients with myocardial infarction, measured peak CRP is associated with new cardiovascular events. Despite an association with peak CRP neither more pronounced platelet aggregation nor PFA-100 closure times independently predict new cardiovascular events.

Dynamics of platelet activation in diabetic and non-diabetic subjects during the course of an acute myocardial infarction.

INTRODUCTION: The dynamics of platelet activation during the course of a myocardial infarction is unknown but of great importance in terms of risk assessment and anti-thrombotic therapy. The aim of the present study was sequentially to analyse platelet activation in diabetic and non-diabetic subjects with an acute myocardial infarction. MATERIALS AND METHODS: We used a sensitive laser light scattering technique to assess platelet aggregation as a measure of activation. Measurements were made on the first, second, third and fifth day in-hospital. Two hundred and forty-three patients with an acute myocardial infarction, of whom 48 had diabetes, were included. RESULTS: Platelet activation increased until the third in-hospital day in both diabetic and non-diabetic subjects, despite intense anti-thrombotic therapy. The activation was more pronounced in diabetic subjects from the time of hospital admission. Platelet activation tended to decrease after the third in-hospital day. CONCLUSIONS: We conclude that platelet activation increases rapidly at the onset of a myocardial infarction, despite aggressive anti-thrombotic treatment. The activation is more pronounced in diabetic subjects and tends to decrease within a few days. More targeted and effective anti-platelet therapy has the potential further to reduce cardiac and cerebral ischemic events following myocardial infarction and ongoing clinical trials are addressing this issue.