Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction.

BACKGROUND: Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. METHODS: In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. RESULTS: From September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P = 0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%. CONCLUSIONS: Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.).

Lifeday coverage of oral anticoagulants and one-year relative survival in patients with atrial fibrillation: a population-based study in Estonia.

BACKGROUND: Routine oral anticoagulation (OAC) is recommended for almost all high-risk patients with atrial fibrillation, yet registries show that OACs are still underused. Our aim was to study the lifeday coverage (LDC) of OAC prescriptions and its relationship with one-year mortality rates of AF patients aged ≥ 65 in Estonia for the years 2019 and 2020. METHODS: Medical data for AF patients aged ≥ 65 years from 2018 and alive as of 01.01.2019 (cohort I) and new AF documentation from 2019 and alive as of 01.01.2020 (cohort II) was obtained from the Health Insurance Fund's electronic database. The data was linked to the nationwide Estonian Medical Prescription Centre's database of prescribed OACs. For LDC analysis, daily doses of guideline-recommended OACs were used. The patients were categorized into three LDC groups: 0%, 1-79%, and ≥ 80%. The data was linked to the Estonian Causes of Death Registry to establish the date of death and mortality rate for the whole Estonian population aged ≥ 65. RESULTS: There were 34,018 patients in cohort I and 9,175 patients with new AF documentation (cohort II), previously not included in cohort I. Of the patients, 77.7% and 68.6% had at least one prescription of OAC in cohorts I and II respectively. 57.4% in cohort I and 44.5% in cohort II had an LDC of ≥ 80%. The relative survival estimates at 1 year for LDC lifeday coverage groups 0%, 1-79%, and ≥ 80% were 91.2%, 98.2%, and 98.5% (cohort I), and 91.9%, 95.2%, and 97.6% (cohort II), respectively. CONCLUSIONS: Despite clear indications for OAC use, LDC is still insufficient and anticoagulation is underused for stroke prevention in Estonia. Further education of the medical community and patients is needed to achieve higher lifeday coverage of prescribed OACs.

Reperfusion therapies and in-hospital outcomes for ST-elevation myocardial infarction in Europe: the ACVC-EAPCI EORP STEMI Registry of the European Society of Cardiology.

AIMS: The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset <24 h in 196 centres across 29 countries. A total of 11 462 patients were enrolled, for whom primary percutaneous coronary intervention (PCI) (total cohort frequency: 72.2%, country frequency range 0-100%), fibrinolysis (18.8%; 0-100%), and no reperfusion therapy (9.0%; 0-75%) were performed. Corresponding in-hospital mortality rates from any cause were 3.1%, 4.4%, and 14.1% and overall mortality was 4.4% (country range 2.5-5.9%). Achievement of quality indicators for reperfusion was reported for 92.7% (region range 84.8-97.5%) for the performance of reperfusion therapy of all patients with STEMI <12 h and 54.4% (region range 37.1-70.1%) for timely reperfusion. CONCLUSIONS: The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality.

Adherence to recommendations for secondary prevention medications after myocardial infarction in Estonia: comparison of real-world data from 2004 to 2005 and 2017 to 2018.

BACKGROUND: Relatively high rates of adherence to myocardial infarction (MI) secondary prevention medications have been reported, but register-based, objective real-world data is scarce. We aimed to analyse adherence to guideline-recommended medications for secondary prevention of MI in 2017 to 2018 (period II) and compare the results with data from 2004 to 2005 (period I) in Estonia. METHODS: Study populations were formed based on data from the Estonian Health Insurance Fund's database and on Estonian Myocardial Infarction Register. By linking to the Estonian Medical Prescription Centre database adherence to guideline-recommended medications for MI secondary prevention was assessed for 1 year follow-up period from the first hospitalization due to MI. Data was analysed using the defined daily dosages methodology. RESULTS: Total of 6694 and 6060 cases of MI were reported in periods I and II, respectively. At least one prescription during the follow up period was found for beta-blockers in 81.0% and 83.5% (p = 0.001), for angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) in 76.9% and 66.0% (p < 0.001), and for statins in 44.0% and 67.0% (p < 0.001) of patients in period I and II, respectively. P2Y12 inhibitors were used by 76.4% of patients in period II. The logistic regression analysis adjusted to gender and age revealed that some drugs and drug combinations were not allocated similarly in different age and gender groups. CONCLUSIONS: In Estonia, adherence to MI secondary prevention guideline-recommended medications has improved. But as adherence is still not ideal more attention should be drawn to MI secondary prevention through systematic guideline implementation.

Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia.

PURPOSE: Large-scale, population-based biobanks integrating health records and genomic profiles may provide a platform to identify individuals with disease-predisposing genetic variants. Here, we recall probands carrying familial hypercholesterolemia (FH)-associated variants, perform cascade screening of family members, and describe health outcomes affected by such a strategy. METHODS: The Estonian Biobank of Estonian Genome Center, University of Tartu, comprises 52,274 individuals. Among 4776 participants with exome or genome sequences, we identified 27 individuals who carried FH-associated variants in the LDLR, APOB, or PCSK9 genes. Cascade screening of 64 family members identified an additional 20 carriers of FH-associated variants. RESULTS: Via genetic counseling and clinical management of carriers, we were able to reclassify 51% of the study participants from having previously established nonspecific hypercholesterolemia to having FH and identify 32% who were completely unaware of harboring a high-risk disease-associated genetic variant. Imaging-based risk stratification targeted 86% of the variant carriers for statin treatment recommendations. CONCLUSION: Genotype-guided recall of probands and subsequent cascade screening for familial hypercholesterolemia is feasible within a population-based biobank and may facilitate more appropriate clinical management.

Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial.

BACKGROUND: REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding. METHODS: We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions. FINDINGS: 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80-1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73-16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19-2·25; p=0·002). INTERPRETATION: The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin. FUNDING: Regado Biosciences Inc.

Improved treatment and prognosis after acute myocardial infarction in Estonia: cross-sectional study from a high risk country.

BACKGROUND: The aim of the study was to explore trends in short- and long-term mortality after hospitalization for acute myocardial infarction (AMI) over the period 2001─2011 in Estonian secondary and tertiary care hospitals while adjusting for changes in baseline characteristics. METHODS: In this nationwide cross-sectional study random samples of patients hospitalized due to AMI in years 2001, 2007 and 2011 were identified and followed for 1 year. Trends in 30-day and 1-year all-cause mortality were analysed using Cox proportional hazards regression model. RESULTS: The final analysis included 423, 687 and 665 patients in years 2001, 2007 and 2011 respectively. During the study period, the prevalence of most comorbidities remained unchanged while the in-hospital and outpatient treatment improved significantly. For example, the proportion of tertiary care hospital AMI patients who underwent revascularization was almost three times higher in 2011 compared to 2001. The proportion of secondary care patients who were referred to a tertiary care centre for more advanced care increased from 5.8 to 40.1 % (p for trend <0.001). Meanwhile, the 1-year mortality rates decreased from 29.5 to 20.2 % (adjusted p = 0.004) in the tertiary and from 32.4 to 23.1 % (adjusted p = 0.006) in the secondary care. The decrease in the 30-day mortality rates was statistically significant only in the secondary care hospitals. CONCLUSIONS: The use of evidence-based treatments in Estonian AMI patients improved between 2001 and 2011. At the same time, we observed a significant reduction in the long-term mortality rates, both for patients primarily hospitalized into secondary as well as into tertiary care hospitals.

Associations between elevated high-sensitive cardiac troponin t and outcomes in patients with acute abdominal pain.

PURPOSE: The purpose of this study was to determine outcomes in patients presenting to emergency department (ED) with acute abdominal pain and suspected occult myocardial injury [OMI (high-sensitive cardiac troponin T, hs-cTnT level > 14 ng/L)] without clinical signs of myocardial ischaemia. We hypothesized that OMI is a common entity associated with poor outcomes. METHODS: After institutional research ethics committee approval, a retrospective review was performed on patients subjected to extended use of hs-cTnT measurements during two months period in patients admitted to ED with a chief complaint of abdominal pain, aged 30 years or older and triaged to red, orange, or yellow categories. Primary outcomes were 30-day, six-month, and one-year mortality, respectively. Adjusted mortality rates were compared using the Cox proportional hazard regression model. RESULTS: Overall, 1000 consecutive patients were screened. A total of 375 patients were subjected to hs-cTnT measurement and 156 of them (41.6%) experienced OMI. None of the patients had acute myocardial infarction diagnosed in the ED. Patients with OMI had a significantly higher 30-day, six-month and one-year mortality compared to the normal hs-cTnT level group [12.8% (20/156) vs. 3.7% (8/219), p = 0.001, 34.0% (53/156) vs. 6.9% (15/219), p < 0.001 and 39.1% (61/156) vs. 9.1 (20/219), p < 0.001, respectively]. OMI was an independent risk factor for mortality at every time point analyzed. CONCLUSION: Our investigation noted OMI in older patients with co-morbidities and in higher triage category presenting with abdominal pain to ED, respectively. OMI is an independent risk factor for poor outcomes that warrants appropriate screening and management strategy. Our results support the use of hs-cTnT as a prognostication tool in this subgroup of ED patients.

Design and rationale of randomized evaluation of decreased usage of beta-blockers after acute myocardial infarction (REDUCE-AMI).

AIMS: Most trials showing benefit of beta-blocker treatment after myocardial infarction (MI) included patients with large MIs and are from an era before modern biomarker-based MI diagnosis and reperfusion treatment. The aim of the randomized evaluation of decreased usage of beta-blockers after acute myocardial infarction (REDUCE-AMI) trial is to determine whether long-term oral beta-blockade in patients with an acute MI and preserved left ventricular ejection fraction (EF) reduces the composite endpoint of death of any cause or recurrent MI. METHODS AND RESULTS: It is a registry-based, randomized, parallel, open-label, multicentre trial performed at 38 centres in Sweden, 1 centre in Estonia, and 6 centres in New Zealand. About 5000 patients with an acute MI who have undergone coronary angiography and with EF ≥ 50% will be randomized to long-term treatment with beta-blockade or not. The primary endpoint is the composite endpoint of death of any cause or new non-fatal MI. There are several secondary endpoints, including all-cause death, cardiovascular death, new MI, readmission because of heart failure and atrial fibrillation, symptoms, functional status, and health-related quality of life after 6-10 weeks and after 1 year of treatment. Safety endpoints are bradycardia, AV-block II-III, hypotension, syncope or need for pacemaker, asthma or chronic obstructive pulmonary disease, and stroke. CONCLUSION: The results from REDUCE-AMI will add important evidence regarding the effect of beta-blockers in patients with MI and preserved EF and may change guidelines and clinical practice.

Care of patients with ST-elevation myocardial infarction: an international analysis of quality indicators in the acute coronary syndrome STEMI Registry of the EURObservational Research Programme and ACVC and EAPCI Associations of the European Society of Cardiology in 11 462 patients.

AIMS: To use quality indicators to study the management of ST-segment elevation myocardial infarction (STEMI) in different regions. METHODS AND RESULTS: Prospective cohort study of STEMI within 24 h of symptom onset (11 462 patients, 196 centres, 26 European Society of Cardiology members, and 3 affiliated countries). The median delay between arrival at a percutaneous cardiovascular intervention (PCI) centre and primary PCI was 40 min (interquartile range 20-74) with 65.8% receiving PCI within guideline recommendation of 60 min. A third of patients (33.2%) required transfer from their initial hospital to one that could perform emergency PCI for whom only 27.2% were treated within the quality indicator recommendation of 120 min. Radial access was used in 56.6% of all primary PCI, but with large geographic variation, from 76.4 to 9.1%. Statins were prescribed at discharge to 98.7% of patients, with little geographic variation. Of patients with a history of heart failure or a documented left ventricular ejection fraction ≤40%, 84.0% were discharged on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and 88.7% were discharged on beta-blockers. CONCLUSION: Care for STEMI shows wide geographic variation in the receipt of timely primary PCI, and is in contrast with the more uniform delivery of guideline-recommended pharmacotherapies at time of hospital discharge.

Sex-specific outcomes of diabetic patients with acute myocardial infarction who have undergone percutaneous coronary intervention: a register linkage study.

BACKGROUND: The presence of diabetes mellitus poses a challenge in the treatment of patients with acute myocardial infarction (AMI). We aimed to evaluate the sex-specific outcomes of diabetic and non-diabetic patients with AMI who have undergone percutaneous coronary intervention (PCI). METHODS: Data of the Estonian Myocardial Infarction Registry for years 2006-2009 were linked with the Health Insurance Fund database and the Population Registry. Hazard ratios (HRs) with the 95% confidence intervals (CIs) for the primary composite outcome (non-fatal AMI, revascularization, or death whichever occurred first) and for the secondary outcome (all cause mortality) were calculated comparing diabetic with non-diabetic patients by sex. RESULTS: In the final study population (n=1652), 14.6% of the men and 24.0% of the women had diabetes. Overall, the diabetics had higher rates of cardiovascular risk factors, co-morbidities, and 3-4 vessel disease among both men and women (p<0.01). Among women, the diabetic patients were younger, they presented later and less often with typical symptoms of chest pain than the non-diabetics (p<0.01). Women with diabetes received aspirin and reperfusion for ST-segment elevation AMI less often than those without diabetes (p<0.01). During a follow-up of over two years, in multivariate analysis, diabetes was associated with worse outcomes only in women: the adjusted HR for the primary outcome 1.44 (95% CI 1.05-1.96) and for the secondary outcome 1.83 (95% CI 1.17-2.89). These results were largely driven by a high (12.0%) mortality during hospitalization of diabetic women. CONCLUSIONS: Diabetic women with AMI who have undergone PCI are a high-risk group warranting special attention in treatment strategies, especially during hospitalization. There is a need to improve the expertise to detect AMI earlier, decrease disparities in management, and find targeted PCI strategies with adjunctive antithrombotic regimes in women with diabetes.

The Estonian Society of Cardiology.

Dr T. Marandi, President 2009­2011, discusses the role of this young society in a small Northern European nation

Evaluation of DOAC Dipstick Test for Detecting Direct Oral Anticoagulants in Urine Compared with a Clinically Relevant Plasma Threshold Concentration.

Measuring direct oral anticoagulant (DOAC) concentrations might be necessary in certain clinical situations but is not routinely performed. The DOAC Dipstick is a new rapid test for detecting DOACs in urine. The aim of this study was to evaluate the possible uses and limitations of the DOAC Dipstick and to compare visual analysis and DOASENSE Reader analysis of DOAC Dipstick pads. Plasma and urine samples were collected from 23 patients taking DOACs. DOAC concentrations in plasma and urine were measured by chromogenic substrate assays and in urine also by the DOAC Dipstick. Plasma concentrations were dichotomized at a threshold of ≥30 ng/mL. Patient samples were compared with samples from control individuals not using anticoagulants (n = 10) and with DOASENSE control urines. The Combur-10 test was used to measure parameters that may affect urine color and hence the interpretation of the DOAC Dipstick result. DOAC Dipstick test results were positive in 21/23 patient urine samples at a plasma DOAC concentration of ≥30 ng/mL and in 2/23 patient urine samples at a plasma DOAC concentration of <30 ng/mL. Inter-observer agreement was above 90% for visual analysis of patient urine samples and was 100% for DOASENSE Reader analysis of patient urines and for analysis of control group urines and DOASENSE control urines. Abnormalities in urine color detected by the Combur-10 test did not affect the DOAC Dipstick results. DOAC Dipstick detects DOACs in urine at a plasma threshold of ≥30 ng/mL. Positive DOAC Dipstick results should be confirmed by measuring DOAC plasma concentration.

Comparison of management and outcomes of ST-segment elevation myocardial infarction patients in Estonia, Hungary, Norway, and Sweden according to national ongoing registries.

AIMS: Describe the characteristics, management and outcomes of hospitalized ST-segment elevation myocardial infarction (STEMI) patients according to national ongoing myocardial infarction registries in Estonia, Hungary, Norway, and Sweden. METHODS AND RESULTS: Country-level aggregated data was used to study baseline characteristics, use of in-hospital procedures, medications at discharge, in-hospital complications, 30-day and 1-year mortality for all patients admitted with STEMI during 2014-2017 using data from EMIR (Estonia; n = 4584), HUMIR (Hungary; n = 23 685), NORMI (Norway; n = 12 414, data for 2013-2016), and SWEDEHEART (Sweden; n = 23 342). Estonia and Hungary had a higher proportion of women, patients with hypertension, diabetes, and peripheral artery disease compared to Norway and Sweden. Rates of reperfusion varied from 75.7% in Estonia to 84.0% in Sweden. Rates of recommendation of discharge medications were generally high and similar. However, Estonia demonstrated the lowest rates of dual antiplatelet therapy (78.1%) and statins (86.5%). Norway had the lowest rates of beta-blockers (80.5%) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (61.5%). The 30-day mortality rates ranged between 9.9% and 13.4% remaining lowest in Sweden. One-year mortality rates ranged from 14.8% in Sweden and 16.0% in Norway to 20.6% in Hungary and 21.1% in Estonia. Age-adjusted lethality rates were highest for Hungary and lowest for Sweden. CONCLUSION: This inter-country comparison of data from four national ongoing European registries provides new insights into the risk factors, management and outcomes of patients with STEMI. There are several possible reasons for the findings, including coverage of the registries and variability of baseline-characteristics' definitions that need to be further explored.

Differences in characteristics, treatments and outcomes in patients with non-ST-elevation myocardial infarction: novel insights from four national European continuous real-world registries.

AIMS: To study baseline characteristics, in-hospital managements and mortality of non-ST-elevation myocardial infarction (NSTEMI) patients in different European countries. METHODS AND RESULTS: NSTEMI patients enrolled in the national myocardial infarction (MI) registries [EMIR; n = 5817 (Estonia), HUMIR; n = 30 787 (Hungary), NORMI; n = 33 054 (Norway), and SWEDEHEART; n = 49 533 (Sweden)] from 2014 to 2017 were included and presented as aggregated data. The median age at admission ranged from 70 to 75 years. Current smoking status was numerically higher in Norway (24%), Estonia (22%), and Hungary (19%), as compared to Sweden (17%). Patients in Hungary had a high rate of diabetes mellitus (37%) and hypertension (84%). The proportion of performed coronary angiographies (58% vs. 75%) and percutaneous coronary interventions (38% vs. 56%), differed most between Norway and Hungary. Prescription of dual antiplatelet therapy at hospital discharge ranged from 60% (Estonia) to 81% (Hungary). In-hospital death ranged from 3.5% (Sweden) to 9% (Estonia). The crude mortality rate at 1 month was 12% in Norway and 5% in Sweden (5%), whereas the 1-year mortality rates were similar (20-23%) in Hungary, Estonia, and Norway and 15% in Sweden. CONCLUSION: Cross-comparisons of four national European MI registries provide important data on differences in risk factors and treatment regiments that may explain some of the observed differences in death rates. A unified European continuous MI registry could be an option to better understand how implementation of guideline-recommended therapy can be used to reduce the burden of cardiovascular disease.

Sex-related differences in the management and outcomes of patients hospitalized with ST-elevation myocardial infarction: a comparison within four European myocardial infarction registries.

Aims: Data on how differences in risk factors, treatments, and outcomes differ between sexes in European countries are scarce. We aimed to study sex-related differences regarding baseline characteristics, in-hospital managements, and mortality of ST-elevation myocardial infarction (STEMI) patients in different European countries. Methods and results: Patients over the age of 18 with STEMI who were treated in hospitals in 2014-17 and registered in one of the national myocardial infarction registers in Estonia (n = 5817), Hungary (n = 30 787), Norway (n = 33 054), and Sweden (n = 49 533) were included. Cardiovascular risk factors, hospital treatment, and recommendation of discharge medications were obtained from the infarction registries. The primary outcome was mortality, in-hospital, after 30 days and after 1 year. Logistic and cox regression models were used to study the associations of sex and outcomes in the respective countries. Women were older than men (70-78 and 62-68 years, respectively) and received coronary angiography, percutaneous coronary intervention, left ventricular ejection fraction assessment, and evidence-based drugs to a lesser extent than men, in all countries. The crude mortality in-hospital rates (10.9-15.9 and 6.5-8.9%, respectively) at 30 days (13.0-19.9 and 8.2-10.9%, respectively) and at 1 year (20.3-28.1 and 12.4-17.2%, respectively) after hospitalization were higher in women than in men. In all countries, the sex-specific differences in mortality were attenuated in the adjusted analysis for 1-year mortality. Conclusion: Despite improved awareness of the sex-specific inequalities on managing patients with acute myocardial infarction in Europe, country-level data from this study show that women still receive less guideline-recommended management.

Do Biobank Recall Studies Matter? Long-Term Follow-Up of Research Participants With Familial Hypercholesterolemia.

Recall-by-genotype (RbG) studies conducted with population-based biobank data remain urgently needed, and follow-up RbG studies, which add substance to this research approach, remain solitary. In such studies, potentially disease-related genotypes are identified and individuals with those genotypes are recalled for consultation to gather more detailed clinical phenotypic information and explain to them the meaning of their genetic findings. Familial hypercholesterolemia (FH) is among the most common autosomal-dominant single-gene disorders, with a global prevalence of 1 in 500 (Nordestgaard et al., Eur. Heart J., 2013, 34 (45), 3478-3490). Untreated FH leads to lifelong elevated LDL cholesterol levels, which can cause ischemic heart disease, with potentially fatal consequences at a relatively early age. In most cases, the pathogenesis of FH is based on a defect in one of three LDL receptor-related genes-APOB, LDLR, and PCSK9. We present our first long-term follow-up RbG study of FH, conducted within the Estonian Biobank (34 recalled participants from a pilot RbG study and 291 controls harboring the same APOB, LDLR, and PCSK9 variants that were included in the pilot study). The participants' electronic health record data (FH-related diagnoses, lipid-lowering treatment prescriptions) and pharmacogenomic risk of developing statin-induced myopathy were assessed. A survey was administered to recalled participants to discern the impact of the knowledge of their genetic findings on their lives 4-6 years later. Significant differences in FH diagnoses and lipid-lowering treatment prescriptions were found between the recalled participants and controls (34 and 291 participants respectively). Our study highlights the need for more consistent lipid-lowering treatment adherence checkups and encourage more follow-up RbG studies to be performed.

Use of evidence-based pharmacotherapy after myocardial infarction in Estonia.

BACKGROUND: Mortality from cardiovascular disease in Estonia is among the highest in Europe. The reasons for this have not been clearly explained. Also, there are no studies available examining outpatient drug utilization patterns in patients who suffered from acute myocardial infarction (AMI) in Estonia. The objective of the present study was to examine drug utilization in different age and gender groups following AMI in Estonia. METHODS: Patients admitted to hospital with AMI (ICD code I21-I22) during the period of 01.01.2004-31.12.2005 and who survived more than 30 days were followed 365 days from the index episode. Data about reimbursed prescriptions of beta-blockers (BBs), angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (ACE/ARBs) and statins for these patients was obtained from the database of the Estonian Health Insurance Fund. Data were mainly analysed using frequency tables and, where appropriate, the Pearson's chi2 test, the Mann-Whitney U-test and the t-test were used. A logistic regression method was used to investigate the relationship between drug allocation and age and gender. We presented drug utilization data as defined daily dosages (DDD) per life day in four age groups and described proportions of different combinations used in men and women. RESULTS: Four thousand nine hundred patients were hospitalized due to AMI and 3854 of them (78.7%) were treated by BBs, ACE/ARBs and/or statins. Of the 4025 inpatients who survived more than 30 days, 3799 (94.4%) were treated at least by the one of drug groups studied. Median daily dosages differed significantly between men and women in the age group 60-79 years for BBs and ACE/ARBs, respectively. Various combinations of the drugs studied were not allocated in equal proportions for men and women, although the same combinations were the most frequently used for both genders. The logistic regression analysis adjusted to gender and age revealed that some combinations of drugs were not allocated similarly in different age and gender groups. CONCLUSIONS: Most of the patients were prescribed at least one of commonly recommended drugs. Only 40% of them were treated by combinations of beta-blockers, ACE inhibitors/angiotensin II receptor blockers and statins, which is inconsistent with guideline recommendations in Estonia. Standards of training and quality programs in Estonia should be reviewed and updated aiming to improve an adherence to guidelines of management of acute myocardial infarction in all age and gender groups.

Better outcomes for acute myocardial infarction patients first admitted to PCI hospitals in Estonia.

OBJECTIVE: The objective of this study was to compare process of care, in-hospital outcomes, and 1-year mortality of patients with acute myocardial infarction (AMI) first admitted to hospitals with and without percutaneous coronary intervention (PCI) facilities in Estonia in 2007. METHODS: We conducted a retrospective cross-sectional study on a random sample of hospitalized AMI patients. Data on process of care and in-hospital outcomes were abstracted from patient records in 16 hospitals according to a standardized study form. RESULTS: Patients first admitted to PCI hospitals (n = 327) had higher rates of overall use of coronary angiography (78.3% vs. 24.7%; P < 0.001), revascularization (64.2% vs. 20.6%; P < 0.001), and echocardiography (85.3% vs. 65.3%, P < 0.001) than those first admitted to non-PCI hospitals (n = 360). Among the non-PCI hospital patients those selected for cardiac catheterization were younger, healthier, and had better clinical status on presentation. Patients admitted to PCI hospitals had higher prescription rates of in-hospital and discharge evidence-based medications except for beta-blockers. PCI hospitals' patients had lower in-hospital mortality (11.3% vs. 19.2%, P = 0.004) and 1-year mortality (24.5% vs. 34.7%, P = 0.003), results remained significant after adjustment for baseline characteristics (odds ratio 0.47; 95% confidence interval 0.28-0.78, hazard ratio 0.66; 95% confidence interval 0.48-0.90). CONCLUSIONS: There are disparities in process of care, in-hospital and 1-year mortality between patients first admitted to PCI vs. non-PCI hospitals in Estonia. Patients admitted to non-PCI hospitals should undergo more vigorous risk stratification using invasive and non-invasive methods; use of evidence-based medicine should be encouraged even if cardiac revascularization is not done.

Estimating the performance of three cardiovascular disease risk scores: the Estonian Biobank cohort study.

BACKGROUND: We aim to investigate the predictive ability of PCE (Pooled Cohort Equations), QRISK2 and SCORE (Systematic COronary Risk Estimation) scoring systems for atherosclerotic cardiovascular disease (ASCVD) risk prediction in Estonia, a country with one of the highest ASCVD event rates in Europe. METHODS: Seven-year risk estimates were calculated in risk score-specific subsets of the Estonian Biobank cohort. Calibration was assessed by standardised incidence ratios (SIRs) and discrimination by Harrell's C-statistics. In addition, a head-to-head comparison of the scores was performed in the intersection of the three score-specific subcohorts. RESULTS: PCE, QRISK2 and SCORE risk estimates were calculated for 4356, 7191 and 3987 eligible individuals, respectively. During the 7-year follow-up, 220 hard ASCVD events (PCE outcome), 671 ASCVD events (QRISK2 outcome) and 94 ASCVD deaths (SCORE outcome) occurred among the score-specific subsets of the cohort. While PCE (SIR 1.03, 95% CI 0.90 to 1.18) and SCORE (SIR 0.99, 95% CI 0.81 to 1.21) were calibrated well for the cohort, QRISK2 underestimated the risk by 48% (SIR 0.52, 95% CI 0.48 to 0.56). In terms of discrimination, PCE (C-statistic 0.778) was inferior to QRISK2 (C-statistic 0.812) and SCORE (C-statistic 0.865). All three risk scores performed at similar level in the head-to-head comparison. CONCLUSION: Of three widely used ASCVD risk scores, PCE and SCORE performed at acceptable level, while QRISK2 underestimated ASCVD risk markedly. These results highlight the need for evaluating the accuracy of ASCVD risk scores prior to use in high-risk populations.