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The effectiveness of lipid-lowering therapy (LLT) for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in routine care may depend on treatment intensity and adherence. Observational study of adults with newly initiated LLT for primary prevention of ASCVD in Stockholm, Sweden, during 2017-2021. Study exposures were LLT adherence [proportion of days covered (PDC)], LLT intensity (expected reduction of LDL cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity were calculated during the previous 12 months, and the patients estimated ASCVD risk was categorized. Study outcomes were major adverse cardiovascular events (MACE) and LDL-C goal attainment. Thirty-six thousand two hundred eighty-three individuals (mean age 63 years, 47% women, median follow-up 2 years), with a baseline low-moderate (40%), high (49%), and very-high (11%) ASCVD risk started LLT. Increases in LLT adherence, intensity, or adherence-adjusted intensity of 10% over 1 year were associated with lower risks of MACE (with hazard ratios of 0.95 [95% CI, 0.93-0.98]; 0.93 [0.86-1.00]; and 0.90 [0.85-0.95], respectively) and higher odds of attaining LDL goals. Patients with good adherence (≥80%) had similar risks of MACE and similar odds ratios for LDL-C goal attainment with low-moderate and high-intensity LLT. Treatment discontinuation was associated with increased MACE risk. The relative and absolute benefits of good adherence were greatest in patients with very high ASCVD risk. In routine-care primary prevention, better adherence to LLT was associated with a lower risk of MACE across all treatment intensities. Improving adherence is especially important among patients with very high ASCVD risk. [ABSTRACT FROM AUTHOR]

Purpose: Database heterogeneity can impact effect estimates. Harmonisation provided by common protocols and common data models (CDMs) can increase the validity of pharmacoepidemiologic research. In a case study measuring the changes in the safety and effectiveness of stroke prevention therapy after the introduction of direct oral anticoagulants (DOACs), we performed an international comparison. Methods: Using data from Stockholm, Denmark, Scotland and Norway, harmonised with a common protocol and CDM, two calendar‐based cohorts were created: 2012 and 2017. Patients with a diagnosis code of atrial fibrillation 5 years preceding the 1‐year cohort window were included. DOAC, vitamin K antagonist and aspirin treatment were assessed in the 6 months prior to the start of each year while strokes and bleeds were assessed during the year. A Poisson regression generated incidence rate ratios (IRRs) to compare outcomes from 2017 to 2012 adjusted for changes in individual‐level baseline characteristics. Results: In 280 359 patients in the 2012 cohort and 356 779 in the 2017 cohort, treatment with OACs increased on average from 45% to 65%, while treatment with aspirin decreased from 30% to 10%. In all countries except Scotland, there were decreases in the risk of stroke and no changes in bleeding risk, after adjustment for changes in baseline characteristics. In Scotland, major bleeding (IRR 1.09, 95% confidence interval [CI] [1.00; 1.18]) and intracranial haemorrhage (IRR 1.31, 95% CI [1.13; 1.52]) increased from 2012 to 2017. Conclusions: Stroke prevention therapy improved from 2012 to 2017 with a corresponding reduction in stroke risk without increasing the risk of bleeding in all countries, except Scotland. The heterogeneity that remains after methodological harmonisation can be informative of the underlying population and database. [ABSTRACT FROM AUTHOR]

Background: To examine patterns of lipid-lowering therapy (LLT) use, and persistence and adherence among patients with coronary heart disease and their associations with lipoprotein cholesterol (LDL-C) goal attainment.Methods: Observational study among 26,768 patients who had suffered a myocardial infarction or had been revascularized in Stockholm during 2012 to 2018, and followed up through 2019. Outcomes included initiation of LLT, discontinuation, re-initiation, adherence to treatment and LDL-C goal attainment according to the European dyslipidaemia guidelines from 2011 and 2016 (mainly LDL-C <1.8 mmol/L).Results: 82% of patients commenced or continued LLT within 90 days after discharge. Of those, 71% were dispensed an LLT prescription within 30 days (62% of them for high-intensity LLT). High-intensity LLT prescribing increased over time, from 12% in 2012 to 78% in 2018. During a median follow-up of 3 (IQR 2-5) years 73% continued to fill prescriptions for a statin, 26.3% temporarily or permanently discontinued, and 0.5% changed to non-statin LLT. Only 1.3% discontinued statin treatment permanently. Throughout observation, about 80% of patients showed good statin adherence (proportion of days covered ≥80%). LDL-C target attainment was 52% the first year and <50% during subsequent years. LDL-C goal attainment was highest among patients receiving high-intensity statin treatment and showing good treatment adherence.Conclusion: In secondary prevention for patients with established coronary heart disease, the proportion of LDL-C target attainment was low throughout the time period of the study, despite increasing use of high-intensity LLT and good treatment persistence and adherence. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Platelet activation, endothelial dysfunction and inflammation may be involved in early stages of diabetic microangiopathy. We therefore investigated patients with Type 1 diabetes mellitus, without (n=19) and with (n=20) microangiopathy, matched for glycaemic control and duration of disease, and matched with healthy control subjects (n=27). Methods. Platelet activation was measured as platelet P-selectin expression using whole blood flow cytometry and as soluble P-selectin by immunoassay. Von Willebrand factor antigen in plasma, serum soluble E-selectin, CD40 ligand (sCD40L) and C-reactive protein (CRP) served as markers for endothelial function and inflammation. Results. Thrombin-induced platelet P-selectin expression was enhanced, and soluble P-selectin and sCD40L concentrations were increased in patients with microangiopathy compared with the control subjects (p<0.01 for both) and with patients without microangiopathy (p<0.05 for P-selectin expression and sP-selectin), whereas all three parameters were similar in patients without microangiopathy and in the control subjects. CRP and soluble E-selectin were increased in patients with microangiopathy, compared with the control subjects (p<0.01 and p<0.05), whereas von Willebrand factor did not differ between the groups. Conclusions/interpretation. Microangiopathy in Type 1 diabetes is associated with platelet hyperactivity, endothelial dysfunction and low-grade inflammation, indicating an increased risk for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: To assess the prognostic impact of autonomic activity, as reflected by catecholamines and heart rate variability (HRV), in patients with stable angina pectoris.Design: Double blind, randomised treatment with metoprolol or verapamil. 24 hour ambulatory ECG, used for frequency domain analyses of HRV, and symptom limited exercise tests at baseline and after one month of treatment. Catecholamine concentrations were measured in plasma (rest and exercise) and urine.Setting: Single centre at a university hospital.Patients: 641 patients (449 men) with stable angina pectoris.Main Outcome Measures: Cardiovascular (CV) death, non-fatal myocardial infarction (MI).Results: During follow up (median 40 months) there were 27 CV deaths and 26 MIs. Patients who died of CV causes had lower total power and high (HF), low (LF), and very low (VLF) frequency components of HRV. HRV was not altered in patients who suffered non-fatal MI. Catecholamines did not differ between patients with and those without events. Metoprolol increased HRV. Verapamil decreased noradrenaline (norepinephrine) excretion. Multivariate Cox analyses showed that total power, HF, LF, and VLF independently predicted CV death (also non-sudden death) but not MI. LF:HF ratios and catecholamines were not related to prognosis. Treatment effects on HRV did not influence prognosis.Conclusions: Low HRV predicted CV death but not non-fatal MI. Neither the LF:HF ratio nor catecholamines carried any prognostic information. Metoprolol and verapamil influenced LF, HF, and catecholamines differently but treatment effects were not related to prognosis. [ABSTRACT FROM AUTHOR]

Background Ultrasonographic assessments of intima-media thickness and plaques in the carotid artery are widely used as surrogate markers for coronary atherosclerosis, but prospective evaluations are scarce and appear to be lacking in patients with coronary artery disease. Ultrasonographic evaluations of femoral vascular changes have not been studied prospectively.Methods and Results In the Angina Prognosis Study in Stockholm (APSIS), 809 patients with stable angina pectoris were studied prospectively during double-blind treatment with verapamil or metoprolol. Ultrasonographic assessments of intima-media thickness, lumen diameter and plaques in the carotid and femoral arteries were evaluated in a subgroup of 558 patients (182 females) with a mean age of 60±7 years, and related to the risk of cardiovascular death (n=18) or non-fatal myocardial infarction (n=26), or revascularization (n=70) during follow-up (median 3·0 years). Univariate Cox regression analyses showed that carotid intima-media thickness and plaques were related to the risk of cardiovascular death or myocardial infarction. Femoral intima-media thickness was related to cardiovascular death or myocardial infarction, as well as to revascularization, whereas femoral plaques were only related to the latter. After adjustment for age, sex, smoking, previous cardiovascular disease and lipid status, carotid intima-media thickness failed to predict any cardiovascular event, whereas carotid plaques tended (P=0·056) to predict the risk of cardiovascular death or myocardial infarction. Femoral intima-media thickness (P<0·01) and plaques (P<0·05) were also related to the risk of revascularization after adjustments.Conclusions Carotid and femoral vascular changes were differently related to cardiovascular events. Carotid intima-media thickness was a weak predictor of events, whereas femoral intima-media thickness predicted revascularization. Plaques in the carotid artery were related to cardiovascular death or non-fatal myocardial infarction, whereas plaques in the femoral artery were related to revascularization. Evaluations of plaques provided better prediction than assessments of intima-media thickness in patients with stable angina. [ABSTRACT FROM PUBLISHER]