Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies.

The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1ß monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies. SIGNIFICANCE STATEMENT: The endothelium was initially considered to be a semipermeable biomechanical barrier and gatekeeper of vascular health. In recent decades, a deepened understanding of the biological functions of the endothelium has led to its recognition as a ubiquitous tissue regulating vascular tone, cell behavior, innate immunity, cell-cell interactions, and cell metabolism in the vessel wall. Endothelial dysfunction is the hallmark of cardiovascular, metabolic, and emerging infectious diseases. Pharmacotherapies targeting endothelial dysfunction have potential for treatment of cardiovascular and many other diseases.

Medical Treatment in Coronary Patients: Is there Still a Gender Gap? Results from European Society of Cardiology EUROASPIRE V Registry.

PURPOSE: This study is aimed at investigating gender differences in the medical management of patients with coronary heart disease (CHD). METHODS: Analyses were based on the ESC EORP EUROASPIRE V (European Survey Of Cardiovascular Disease Prevention And Diabetes) survey. Consecutive patients between 18 and 80 years, hospitalized for a coronary event, were included in the study. Information on cardiovascular medication intake at hospital discharge and at follow-up (≥ 6 months to < 2 years after hospitalization) was collected. RESULTS: Data was available for 8261 patients (25.8% women). Overall, no gender differences were observed in the prescription and use of cardioprotective medication like aspirin, beta-blockers, and ACE-I/ARBs (P > 0.01) at discharge and follow-up respectively. However, a statistically significant difference was found in the use of statins at follow-up, in disfavor of women (82.8% vs. 77.7%; P < 0.001). In contrast, at follow-up, women were more likely to use diuretics (31.5% vs. 39.5%; P < 0.001) and calcium channel blockers (21.2% vs. 28.8%; P < 0.001), whereas men were more likely to use anticoagulants (8.8% vs. 7.0%; P < 0.001). Overall, no gender differences were found in total daily dose intake (P > 0.01). Furthermore, women were less likely than men to have received a CABG (20.4% vs. 13.2%; P < 0.001) or PCI (82.1% vs. 74.9%; P < 0.001) at follow-up. No gender differences were observed in prescribed (P = 0.10) and attended (P = 0.63) cardiac rehabilitation programs. CONCLUSION: The EUROASPIRE V results show only limited gender differences in the medical management of CHD patients. Current findings suggest growing awareness about risk in female CHD patients.

Cardiovascular drug use among people with cognitive impairment living in nursing homes in northern Sweden.

PURPOSE: The aim of this study was to describe changes in the pattern of cardiovascular agents used in elderly people living in nursing homes between 2007 and 2013. Further, the aim was to analyse the use of cardiovascular drugs in relation to cognitive impairment and associated factors within the same population, where prescription of loop diuretics was used as a proxy for heart failure. METHODS: Two questionnaire surveys were performed including 2494 people in 2007 and 1654 people in 2013 living in nursing homes in northern Sweden. Data were collected concerning drug use, functioning in activities of daily living (ADL) and cognition, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). The use of different drugs and drug classes among people at four different levels of cognitive function in 2007 and 2013 were compared. RESULTS: The proportion of people prescribed ASA and diuretics was significantly lower at all four levels of cognitive function in 2013 compared to 2007. Among people prescribed loop diuretics, the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARBs) increased from 37.8 to 45.6%, ß-blockers from 36.0 to 41.8% and warfarin from 4.4 to 11.4%. The use of warfarin, ACEI/ARBs, ß-blockers and mineralocorticoid receptor antagonists (MRAs) were less common among individuals with more severe cognitive impairment. CONCLUSION: The results indicate that cardiovascular drug treatment has improved between 2007 and 2013, but there is room for further improvement, especially regarding adherence to guidelines for heart failure. Increasing cognitive impairment had an effect on treatment patterns for heart failure and atrial fibrillation.

Performance of current claims-based approaches to identify aortic dissection hospitalizations.

OBJECTIVE: To describe index visits for acute aortic dissection (AD) to an academic center and validate the prevailing claims-based methodology to identify and stratify them. METHODS: Inpatient hospitalizations at a single center assigned an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code for AD from January 2005 to September 2015 were identified. Diagnoses were verified by review of medical records and imaging studies. All visits were secondarily stratified with the algorithm based on ICD-9 codes. Sensitivity and specificity analyses were conducted to evaluate the ability of the algorithm to correctly identify acute AD by Stanford class and treatment modality (type A open repair [TAOR], type B open repair [TBOR], thoracic endovascular repair [TEVAR], medical management [MM]). RESULTS: In the study interval, there were 1245 visits coded for AD attributed to 968 unique patients. Chart review verification demonstrated that the majority of visits were for AD (79%; n = 981), of which 32% (n = 310) were for an index acute AD event. The true distribution of acute AD visit classifications was TAOR (46.1%; n = 143), TBOR (5.2%; n = 16), TEVAR (7.7%; n = 24), and MM (39.4%; n = 122). The algorithm, which used ICD-9 codes, identified 631 acute visits and stratified them as TAOR (27.1%; n = 171), TBOR (4.1%; n = 26), TEVAR (4.9%; n = 31), and MM (63.9%; n = 403). Analyses demonstrated high specificities, but generally low sensitivities of the algorithm (TAOR: sensitivity, 58%, specificity, 92%; TBOR: sensitivity, 13%, specificity, 98%; TEVAR: sensitivity, 17%, specificity, 98%; MM: sensitivity, 73%, specificity, 72%). CONCLUSIONS: The prevalent claims-based strategy to identify hospitalizations with acute AD is specific, but lacks sensitivity. Caution should be exercised when studying AD with ICD-9 codes and improvements to existing claims-based methodologies are necessary to support future study of acute AD.

How Heart Rate Should Be Controlled in Patients with Atherosclerosis and Heart Failure.

PURPOSE OF REVIEW: Resting heart rate is an independent risk factor for all-cause and cardiovascular mortality in patients with heart failure. The main objectives are to discuss the prognosis of heart rate, its association with coronary atherosclerosis, and the modalities of control of the heart rate in sinus rhythm and in the rhythm of atrial fibrillation in patients with chronic heart failure. RECENT FINDINGS: As a therapeutic option for control heart rate, medications such as beta-blockers, digoxin, and finally ivabradine have been studied. Non-dihydropyridine calcium channel blockers are contraindicated in patients with heart failure and reduced ejection fraction. The influence of the magnitude of heart rate reduction and beta-blocker dose on morbidity and mortality will be discussed. Regarding the patients with heart failure and atrial fibrillation, there are different findings in heart rate control with the use of a beta-blocker. Patients eligible for ivabradine have clinical benefits and increased ejection fraction. Vagal nerve stimulation has low efficacy for the control of heart rate. Complementary therapies such as tai chi and yoga showed no effect on heart rate. In this review, we discuss the main therapeutic options for the control of heart rate in patients with atherosclerosis and heart failure. More research is needed to examine the effects of therapeutic options for heart rate control in different population types, as well as their effects on clinical outcomes and impact on morbidity and mortality.

Effect of Oral Nitrates on All-Cause Mortality and Hospitalization in Heart Failure Patients with Reduced Ejection Fraction: A Propensity-Matched Analysis.

BACKGROUND: Hydralazine-nitrate combination is recommended for patients with heart failure with reduced ejection fraction (HFrEF)/systolic heart failure who are symptomatic despite guideline-directed medical therapy (GDMT). Use of nitrates alone for this indication is not well-established. This study aims to evaluate the effect of oral nitrates on all-cause mortality and hospitalization in HFrEF patients using GDMT. METHODS AND RESULTS: Nitrate prescription at discharge and its association with all-cause mortality and heart failure hospitalization were examined in a propensity-matched analysis of 648 HFrEF patients followed for a median of 56 months. A total of 269 (42%) patients died during that period. In Cox regression analysis, nitrate usage was associated with a slightly increased mortality risk compared with not using nitrates (hazard ratio 1.29; 95% confidence interval 1.01-1.65; P = .040), which continued modestly after the propensity-matched analysis (hazard ratio 1.26; 95% confidence interval 0.95-1.68; P = .102). In both prematch and propensity-matched analyses, nitrate use was not associated with risk of rehospitalization. No significant effect was detected on subgroups stratified by coronary artery disease, age, gender, and background medical therapy. CONCLUSIONS: In this study, oral nitrate use alone in addition to GDMT did not affect all-cause mortality and hospitalization risk in HFrEF patients during a long-term follow-up. There was even a modest tendency for increased risk of mortality.

Clinical management and prevention of sudden cardiac death.

Despite the revolutionary advancements in the past 3 decades in the treatment of ventricular tachyarrhythmias with device-based therapy, sudden cardiac death (SCD) remains an enormous public health burden. Survivors of SCD are generally at high risk for recurrent events. The clinical management of such patients requires a multidisciplinary approach from postresuscitative care to a thorough cardiovascular investigation in an attempt to identify the underlying substrate, with potential to eliminate or modify the triggers through catheter ablation and ultimately an implantable cardioverter-defibrillator (ICD) for prompt treatment of recurrences in those at risk. Early recognition of low left ventricular ejection fraction as a strong predictor of death and association of ventricular arrhythmias with sudden death led to significant investigation with antiarrhythmic drugs. The lack of efficacy and the proarrhythmic effects of drugs catalyzed the development and investigation of the ICD through several major clinical trials that proved the efficacy of ICD as a bedrock tool to detect and promptly treat life-threatening arrhythmias. The ICD therapy is routinely used for primary prevention of SCD in patients with cardiomyopathy and high risk inherited arrhythmic conditions and secondary prevention in survivors of sudden cardiac arrest. This compendium will review the clinical management of those surviving SCD and discuss landmark studies of antiarrhythmic drugs, ICD, and cardiac resynchronization therapy in the primary and secondary prevention of SCD.

Medication Initiation Burden Required to Comply With Heart Failure Guideline Recommendations and Hospital Quality Measures.

BACKGROUND: Guidelines for heart failure (HF) recommend prescription of guideline-directed medical therapy before hospital discharge; some of these therapies are included in publicly reported performance measures. The burden of new medications for individual patients has not been described. METHODS AND RESULTS: We used Get With The Guidelines-HF registry data from 2008 to 2013 to characterize prescribing, indications, and contraindications for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, ß-blockers, aldosterone antagonists, hydralazine/isosorbide dinitrate, and anticoagulants. The difference between a patient's medication regimen at hospital admission and that recommended by HF quality measures at discharge was calculated. Among 158 922 patients from 271 hospitals with a primary discharge diagnosis of HF, initiation of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was indicated in 18.1% of all patients (55.5% of those eligible at discharge were not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at admission), ß-blockers in 20.3% (50.5% of eligible), aldosterone antagonists in 24.1% (87.4% of eligible), hydralazine/isosorbide dinitrate in 8.6% (93.1% of eligible), and anticoagulants in 18.0% (58.0% of eligible). Cumulatively, 0.4% of patients were eligible for 5 new medication groups, 4.1% for 4 new medication groups, 9.4% for 3 new medication groups, 10.1% for 2 new medication groups, and 22.7% for 1 new medication group; 15.0% were not eligible for new medications because of adequate prescribing at admission; and 38.4% were not eligible for any medications recommended by HF quality measures. Compared with newly indicated medications (mean, 1.45 ± 1.23), actual new prescriptions were lower (mean, 1.16 ± 1.00). CONCLUSIONS: A quarter of patients hospitalized with HF need to start >1 medication to meet HF quality measures. Systems for addressing medication initiation and managing polypharmacy are central to HF transitional care.

Translation of acute coronary syndrome therapies: from evidence to routine clinical practice.

BACKGROUND: The use of evidence-based therapies has improved the outcome of patients with acute coronary syndrome (ACS), but there is a time lag between the generation of clinical evidence and its application in routine clinical practice. We sought to quantify temporal lags in the lifecycle of American College of Cardiology (ACC)/American Heart Association (AHA) class IA ACS therapies. METHODS: Using current and historical ACC/AHA guideline publications, we retrieved publication dates of pivotal clinical trials (PCTs) and class IA guideline-recommended therapies for patients with ST-elevation myocardial infarction (STEMI) and unstable angina (UA)/non-STEMI (NSTEMI). Clinical practice uptake data for each therapy were retrieved from the National Registry for Myocardial Infarction, Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines, and Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines, which are registries containing publicly available peer-reviewed data. Descriptive data were calculated and compared for each phase of the evidence lifecycle for both STEMI and UA/NSTEMI drug classifications. RESULTS: We identified 11 class IA- and 4 class IB/IC-recommended therapies for acute, inhospital, and discharge use for patients with STEMI or UA/NSTEMI. The median time lags were 2 years (interquartile range [IQR], 1-4 years) from PCT to practice guideline recommendation, 14 years (IQR, 11-15 years) from guideline recommendation to 90% practice uptake, and overall, a 16-year median (IQR, 13-19 years) from PCT to 90% practice uptake. CONCLUSIONS: The time of PCT publication to meaningful uptake of class IA ACS therapies into clinical practice took a median of 16 years. This significant time lag indicates systemic barriers to the translation of therapeutics into routine clinical practice.

A real-world perspective on the prevalence and treatment of heart failure with a reduced ejection fraction but no specific or only mild symptoms.

Heart failure (HF) is commonly described according to the severity of symptoms, using the New York Heart Association (NYHA) classification, and the assessment of ventricular function, by measuring the left ventricular ejection fraction (LVEF). It is important to acknowledge, however, that the severity of symptoms does not systematically correlate with the level of ventricular systolic dysfunction. Patients with no or only mild symptoms are still at high risk of HF-related morbidity and mortality. The objective of this review was to summarize the prevalence, characteristics, and treatment of patients with chronic HF and mild or no symptoms and to review epidemiological data from three recent registries conducted in Europe. From a clinical practice perspective, patients with a reduced ejection fraction who have only mild symptoms appear to represent a group of patients for whom the provision of adequate medical care is yet to be optimized. While prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers appears to be consistently high, the use of mineralocorticoid receptor antagonists is more variable and does not appear to be in accordance with the latest clinical guidelines. As approximately half of patients with HF and a reduced LVEF have NYHA class II symptoms, significant reductions in morbidity and mortality could be achieved by more comprehensive treatment of this population.

Drug-coated balloon and stent therapies for endovascular treatment of atherosclerotic superficial femoral artery disease.

Endovascular management of superficial femoral artery disease has historically been limited to percutaneous balloon angioplasty, atherectomy, and bare-metal stents. However, these therapies have been plagued by high restenosis and target lesion revascularization rates. More recent technologies such as drug-coated stents and balloons are designed to combat restenosis by locally delivering antiproliferative drugs. Several randomized controlled trials have directly compared these antiproliferative drug-delivering devices to their non-drug-coated counterparts. Additionally, trials are currently ongoing to compare use of drug-coated technologies in combination with traditional therapies in hope of synergistic effects. This review gathers data from currently published clinical trials, provides an overview of upcoming clinical studies utilizing drug-coated technology, and explores the possible impact these devices may have on clinical practice.

[Prescriptions in patients with coronary artery disease]. / Ordonnance du patient coronarien.

The management of stable coronary artery disease has evolved in recent years and is now based on the latest recommendations of the European Society of Cardiology. Drug prescription takes into account two strategic approaches: on the one hand, pharmacological treatments that improve the prognosis and on the other hand treatments to improve symptoms and/or ischemia. Improving the prognosis involves reducing as well as stabilizing coronary plaque thanks to 3 therapeutic classes: aspirin, statins and renin-angiotensin system blockers (ACE inhibitors or ARBs). In parallel, a fast-acting nitrovasodilator associated with a beta-blocker or a heart-slowing calcium-channel blocker makes it possible to reduce the angina. In addition, pharmacological modifications and regular reassessments are fundamental aspects of CAD management.

Frequency of angina and quality of life in outpatients with stable coronary artery disease in Turkey: insights from the PULSE study.

OBJECTIVE: Cardiologists' approach to angina in outpatients with stable coronary artery disease (CAD) is unclear. Therefore, we analysed data from the national multicentre, observational PULSE study to evaluate the frequency of angina, clinical variables affecting angina frequency and the impact of frequent angina on quality of life (QoL) in outpatients with stable CAD managed by cardiologists in secondary and tertiary health-care centres in Turkey. METHODS AND RESULTS: Adult outpatients with stable CAD in sinus rhythm were included. Data were collected at a single study visit from 83 centres. Patients were divided into five categories according to angina attack frequency. QoL was measured by the MacNew heart disease health-related QoL Questionnaire. The mean (standard deviation; SD) age of all patients (n = 2661) was 61.2 (10.2) years. Of 2,661 patients, 48.7% had no anginal attacks while 16.5% had minimal, 14.5% occasional, 12.2% regular and 8.1% frequent attacks. Angina attack frequency correlated positively with female sex, heart rate, the severity of angina. Emotional, physical, social, and global scores of QoL tended to decrease across angina attack frequency categories. Short- and long-acting nitrates, ivabradine were significantly more preferred in patients with higher frequency of angina attacks rather than beta blockers and calcium channel blockers. CONCLUSIONS: Insufficient angina control in outpatients with stable CAD requires reassessment of medical approach since it has a negative impact on QoL. The social and economic consequences of this burden should be sought on a national basis.

[The ability to use meldonium as adaptogen in winter in patients with cardiovascular disease].

Given that the effects of frost can play the role of independent stress factor influencing the course of cardiovascular disease (CVD), it is reasonable to supplementation of drugs that increase the body's resistance to cold stress. Aim: To evaluate the possibility of using meldonium to prevent unwanted seasonal changes in CVD patients in the winter. The study included 49 patients with CVD aged 38-75 years. Patients were randomized into 2 groups: active management (M), in which in addition to the basic therapy received during the winter 3 months meldonium 1000 mg/day, and a control (K). We measured office blood pressure, heart rate, blood chemistry, determination of glycosylation end products (DGP). Filled with a visual analogue scale (VAS) to assess the quality of life (QOL). During frost marked increase in blood glucose (p = 0.02) in group K, persisting throughout the winter, and an increase in tissue DGP in March (p = 0.002). In group M glucose and DGP not significantly raised. In group M at the peak of cold showed a reduction in cholesterol levels. Admission meldonium associated with improved quality of life, in the dynamics of the group K was negative [Δ +10.0 VAS scores in group M versus -7.5 points in the group K in the cold (p = 0.04) and Δ +10,0 points vs -5.0 points, respectively, in March 2014 (p = 0.055)]. Adding to the basic treatment of patients with CVD meldonium in a dose of 1000 mg/day in winter, accompanied by improved quality of life, as well as let negative changes in carbohydrate metabolism.

[Practical aspects of treatment in patients with chronic cerebral ischemia and hypertension in general somatic practice].

The official statistics of the Ministry of Health of the Russian Federation show that the past 10 years have been marked by an increase in the number of patients with chronic cerebral circulatory disorders (CCCD), accounting for at least 700 per 100,000 population. Hypertension is the most studied etiological factor of CCCD. However, its role is often perceived uniquely as the major mechanism for destabilization of the arterial vascular bed. The detailed study of the pathogenesis of impairments in the cerebral vascular bed and neurons will be able to predict the further course of the disease and to choose adequate therapy.

[Clinical guidelines for the diagnosis and treatment of pulmonary hypertension].

Pulmonary hypertension (PH) is a group of diseases characterized by progressive increases in pulmonary vascular resistance and pulmonary artery pressure, which results in right ventricular heart failure and sudden death. Based on the current version of the guidelines for PH diagnosis and treatment, adopted by the experts of the European Society of Cardiology and the European Respiratory Society in 2009, and on the data of Russian and foreign clinical trials, the Russian experts elaborated clinical guidelines for PH in 2013. The latter consider the current classifications of PH, the specific features of its pathogenesis, and its diagnostic algorithm. The section dealing with drugs for maintenance therapy discusses data on the use of oral anticoagulants, diuretics, cardiac glycosides, and oxygen therapy. PH-specific therapy includes calcium antagonists, prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Surgical procedures for PH involve atrial septostomy, thromboendartectomy, and lung or heart-lung transplantation. A treatment algorithm is proposed for PH patients. The current medicinal approaches using specific therapy agents and their combinations offer new promises for the effective treatment of patients with PH and improve its prognosis.

[Conservative treatment of patients with intermittent claudication].

The article deals with the analysis of the results of randomized placebo-controlled studies of various therapeutic agents currently available in Russia, as well as the results of meta-analyses and Cochrane reviews of medicamentous treatment of patients with intermittent claudication. The results of these studies gave grounds to recommend the most efficient agents in the new edition of the "National Guidelines on management of patients with lower-limb arterial disease" (2013).

[Comparison of data from registries of acute coronary syndromes RECORD and RECORD-2: management of patients and its results in noninvasive hospitals].

Positive changes are declared to occur during recent years in management of hospitalized patients with acute coronary syndromes (ACS) in Russia. Most of these changes are related to availability of invasive treatment. But considerable portion of patients (pts) are still treated in hospitals without facilities for invasive myocardial revascularization (noninvasive hospitals - NIHs). Aim of this study was to compare some characteristics of management of ACS in NIHs which participated in ACS registries RECORD (2007-2008, 8 NIHs from 6 cities; n=381) and RECORD-2 (2009-2011, 3 NIHs from 3 cities, n=680). Results. Groups of pts recruited in these NIHs had similar mean age and portion of women (67.6 and 66.5 years, 51.1 and 53.1 % in RECORD-2 and RECORD, respectively, p=0.64). Time from symptoms onset to hospitalization was shorter in RECORD-2 (3.2 vs 4.1 hours for ST-elevation [STE], =0.03; 4.0 vs 6.5 hours for non ST elevation [NSTE] ACS, <0.0001). Among RECORD-2 NSTEACS pts more had ST depressions (50.6 vs 28.7%, <0.0001), high risk of death according to GRACE score (39.1 vs 20.9 %, <0.0001), but less Killip class >II (15.0 vs 21.6%, p=0.025). No such differences existed among STEACS pts. Thrombolysis was more often used in RECORD-2 (62.6 vs 34.1%, <0.0001). Both STEACS and NSTEACS RECORD-2 pts more often received clopidogrel (63.5 vs 18.8%, p<0.0001, and 41.6 vs 11.1%, <0.0001, respectively). More NSTEACS RECORD-2 pts were given parenteral anticoagulants (93.4 vs 80.4%, <0.0001), low molecular weight heparins (23.4 vs. 3.4%, <0.0001) and fondaparinux (10.4 vs 0.7%, <0.0001), but still in 20% of NSTEACS RECORD-2 pts unfractionated heparin was given subcutaneously. Twenty RECORD-2 pts (2.9%) were transferred to invasive hospital but none during first 24 hours. There were no significant differences between registers in hospital mortality (20.0 vs 21.2%, =0.84; 4.2 vs 2.7%, =0.24 in STE and NSTE ACS pts of RECORD-2 and RECORD, respectively). Conclusions. Despite some improvement in management of pts occurring in 2-3 years NIHs mortality in STEACS remained very high. Numerically higher mortality in NSTEACS could be partially attributed to higher risk of RECORD-2 pts.

[Cost of drugs used to treat cardiovascular disease in Brazil]. / Preço dos medicamentos utilizados nas doenças cardiovasculares no Brasil.

OBJECTIVE: Diseases of the circulatory system are a principal cause of mortality in Brazil. Using as a basis drugs dispensed through Brazil's Popular Pharmacy Program (FPB, for its name in Portuguese), prices for drugs used to treat circulatory diseases were analyzed to identify the advantages of using generic drugs and the FPB. METHODS: Drug prices were obtained using Brazil's Pharmacy Price Guide and FPB price tables. The costs of 15 drugs available through the FPB were compared with those of three generic pharmaceutical products, three similar products, and the reference drug. RESULTS: The generic drugs were lower in price for 10 of the drugs and for four of the similar products. The FPB drugs were of the lowest price. CONCLUSIONS: Generic and FPB drugs are easily accessed by the population and thus facilitate the continuity of pharmacotherapy when these drugs are not available through the Unified Health System and/or are not affordable through other means. Access to drugs should be taken into consideration at the time prescriptions are filled, especially as regards those used to treat chronic diseases.

A Comparison of Rate Control Agents for the Treatment of Atrial Fibrillation: Follow-Up Investigation of the AFFIRM Study.

There are limited data from randomized controlled trials comparing rate control agents in atrial fibrillation. Patient-level data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial was used to compare outcomes in patients randomized to the rate control arm who were treated with a single rate control agent at baseline. The rate control agents used were beta-blockers, non-dihydropyridine calcium channel blockers, and digoxin. The independent variable for this analysis was the initial study drug used and the dependent variables were time to first hospitalization and time to death from any cause. We analyzed 1,144 out of 2,027 participants assigned to the rate control group who were on a single rate control agent at the start of the trial. There were 485 (42.5%) participants in the beta-blocker group, 344 (30%) in the calcium channel blocker group, and 315 (27.5%) in the digoxin group. All hospitalization and all-cause mortality occurred in 55.9% and 12.5% of those in the beta-blocker group, 58.4% and 16.7% in the calcium channel blocker group, and 55.2% and 21.1% in the digoxin group, respectively. After adjustment for differences in baseline characteristics, there were no significant differences in time to hospitalization or death for any group. In the AFFIRM trial, the initial rate control drug used was not associated with statistically significant differences in time to hospitalization or death after controlling for differences in baseline characteristics. There is limited data at present to guide the selection of rate control agents in patients with atrial fibrillation.