Blockers In Patients Research Articles

Renal outcomes of treatment with telmisartan in patients with stage 3-4 chronic kidney disease: A prospective, randomized, controlled trial (JINNAGA).

Objectives:Although angiotensin II receptor blockers are effective for patients with chronic kidney disease, dose-dependent renoprotective effects of angiotensin II receptor blockers in patients with moderate to severe chronic kidney disease with non-nephrotic proteinuria are not known. Our aim was to elucidate the dose-dependent renoprotective effects of angiotensin II receptor blockers on such patients.Methods:A multicenter, prospective, randomized trial was conducted from 2009 to 2014. Patients with non-nephrotic stage 3–4 chronic kidney disease were randomized for treatment with either 40 or 80 mg telmisartan and were observed for up to 104 weeks. Overall, 32 and 29 patients were allocated to the 40 and 80 mg telmisartan groups, respectively. The composite primary outcome was renal death, doubling of serum creatinine level, transition to stage 5 chronic kidney disease, and death from any cause. Secondary outcomes included the level of urinary proteins and changes in the estimated glomerular filtration rate.Results:There was no difference in the primary outcome (p = 0.78) and eGFR (p = 0.53) between the two groups; however, after 24 weeks, urinary protein level was significantly lower in the 80 mg group than in the 40 mg group (p < 0.05). No severe adverse events occurred in either group, and the occurrence of adverse events did not significantly differ between them (p = 0.56).Conclusion:Our findings do not demonstrate a direct dose-dependent renoprotective effect of telmisartan. The higher telmisartan dose resulted in a decrease in the amount of urinary protein. Even though high-dose angiotensin II receptor blockers may be preferable for patients with stage 3–4 chronic kidney disease, the clinical importance of the study results may be limited. The study was registered in the UMIN-CTR (https://www.umin.ac.jp/ctr) with the registration number UMIN000040875.

Микроваскулярная стенокардия: патогенез, клиника, диагностика и принципы терапии

The literature review presents current data on some mechanisms of development, clinical picture, diagnosis, and therapy tactics of microvascular angina (MA). The important role of microcirculatory pathology in the genesis of coronary heart disease is emphasized. Endothelial dysfunction and angiospasm have been shown to be the basis of MA. The article presents MA detection, including the presence of myocardial ischemia in the absence of obstructive coronary artery disease (coronary artery disease &lt;50% or fractional flow reserve &gt;0.80). It was noted that Holter monitoring was not informative for reliable diagnosis of myocardial ischemia, since the results of the study did not exclude or confirm the presence of coronary heart disease, including MA. Stress echocardiography and positron emission tomography were highly informative in the diagnosis of myocardial ischemia caused by microvascular pathology. The article also considers drug therapy tactics with the use of beta-adrenergic blocking agents and calcium channel blockers for patients with MA and the low efficacy of nitrates. The role of second-line drugs such as Nicorandil, Ranolazine, and Trimetazidine is discussed. The important role of statins and angiotensin-converting enzyme inhibitors, which have proven to be effective in the treatment of endothelial dysfunction, is emphasized. Disaggregants, like statins, are an important therapy component of MA.KEYWORDS: microvascular angina, endovascular dysfunction, diagnostics, therapy tactics.FOR CITATION: Shmatova E.N., Grinshtein Yu.I. Microvascular angina: pathogenesis, clinical picture, diagnosis and therapy tactics. Russian Medical Inquiry. 2020;4(7):425–430. DOI: 10.32364/2587-6821-2020-4-7-425-430.

Evolution of pathogenetic therapy of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a severe, disabling disease characterized by an increase pressure in the pulmonary artery (PA), an increase pressure in the right atrium, and a decrease of the cardiac output. It combines several diseases: idiopathic pulmonary hypertension, inherited pulmonary hypertension, PAH induced by medication and toxins, PAH associated with systemic diseases of connective tissue, HIV infection, portal hypertension, congenital heart defects, schistosomiasis. In the absence of treatment, PAH quickly leads to insufficiency of the right heart and premature death. An effective PAH therapy did not exist for a long time. However, in 1987 there was established a positive effect of taking large doses of calcium channel blockers in patients, who "responded" to their prescription in the short term, and in recently several groups of specific drugs have been developed and approved for the treatment of this pathology: prostacyclin analogues and prostacyclin receptors agonists, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors and soluble guanylate cyclase stimulators. Modern studies of treatment of PAH are based on the latest data of the molecular transmission mechanisms of intracellular and intercellular signals, the action of hormones and tissue enzymes. The available results of these studies allow to suggest the inclusion to clinical guidelines several new drugs for the pathogenetic treatment of PAH in the near future: receptor tyrosine kinase inhibitors, Rho - kinase inhibitors, immunosuppressants and type 2 activin receptor agonists, protein kinase C inhibitors, aromatase inhibitors and estrogen receptor antagonists, poly-(ADP-ribose)-polymerase inhibitors and bromodomain protein 4, elastase inhibitors. Some of the drugs have already passed the III phase of clinical trials (imatinib), others are at the preclinical stage or at the I-II phase tests (olaparib, enzastaurin, elafin).

Feasibility of Neurohumoral Blocker Withdrawal in Patients Optimally Responding to Cardiac Resynchronization Therapy: An Open-label, Double Randomized Controlled Pilot Trial

Background It remains unclear if medical therapy remains necessary in HF patients with myocardial recovery after CRT in whom conduction delay is thought to be the main driver. Methods This was a prospective multicenter, open-label, double randomized pilot trial to investigate the safety of neurohumoral (NH) blocker withdrawal in HF patients with recovered ejection fraction (HFrecEF) after CRT. Subjects were randomized to systematic withdrawal of RAAS inhibitors and beta blockers (BB) versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling defined by an increase in left ventricular end systolic volume index (LVESVi) of more than 15% at 24 months. The secondary endpoint is a composite safety endpoint of all-cause mortality, HF related hospitalizations and incidence of sustained ventricular arrhythmias at 24 months. The primary analysis was by intention to treat. Results: Between September 24, 2014, and February 15, 2017, 80 subjects were consecutively enrolled and randomized between 4 groups (continuation of NH blocker therapy (n=20), withdrawal of RAAS inhibitors (n=20), withdrawal of BB (n=20) and withdrawal of RAAS inhibitors and BB (n=20)). Of the 80 subjects, 6 (7.5%) met the primary endpoint of recurrence of negative remodeling based on an increase of >15% in LVESVi. The secondary endpoint occurred in 4 subjects (5%) within 24 months. There was no difference between the 4 groups regarding the primary (log rank p=0.497) and secondary endpoint (log rank p=0.507) (Figure 1). There were no hospital admissions due to HF or cardiac deaths during this time period in any subject. However, re-initiation of therapy occurred in 16 (20%) subjects due to hypertension or supraventricular arrhythmias. Conclusion Compared to continuation, withdrawal of NH blockers in patients with myocardial recovery after CRT is not associated with a recurrence of LV dilatation or HF after 2 years. However, the feasibility of NH blocker withdrawal is hampered because of hypertension and supraventricular arrhythmias.

Impact of cardiac function, refractory ascites and beta blockers on the outcome of patients with cirrhosis listed for liver transplantation

Whether non-selective beta blockers (NSBBs) are deleterious in patients with end-stage cirrhosis and refractory ascites has been widely debated. We hypothesized that only the subset of patients on the liver transplant waiting list who had impaired cardiac performance would be at increased risk of mortality if receiving NSBBs. This study included 584 consecutive patients with cirrhosis evaluated for transplantation between 1999 and 2014. All patients had right heart catheterization with hemodynamic measurements at evaluation. Fifty percent received NSBBs. Refractory ascites was present in 33%. Cardiac performance was assessed by left ventricular stroke work index (LVSWI). Waiting list mortality without liver transplantation was explored using competing risk analysis. LVSWI was significantly lower in patients with refractory ascites. In multivariate analysis using competing risk, refractory ascites, NSBBs and LVSWI were associated with waiting list mortality in the whole population, with a statistically significant interaction between NSBBs and LVSWI. The most discriminant value of LVSWI was 64.1g-m/m2. In the final model, refractory ascites (subdistribution hazard ratio 1.52; 95% CI1.01-2.28; p=0.0083) and treatment by NSBBs with LVSWI <64.1g-m/m2 (subdistribution hazard ratio 1.96; 95% CI 1.32-2.90; p=0.0009) were significantly associated with waiting list mortality, taking into account serum sodium and the model for end-stage liver disease score. This study suggests that compromised cardiac performance is more common in patients with refractory ascites and that NSBBs are deleterious in cirrhotic patients with compromised cardiac performance. These results highlight the prognostic value of cardiac function in patients with end-stage cirrhosis. There are still controversies concerning the impact of non-selective beta blockers on outcomes in patients with decompensated cirrhosis, especially in those with refractory ascites. In this study of 584 cirrhotic patients evaluated for liver transplantation, who underwent right heart catheterization, we have shown that global cardiac performance measured by left ventricular stroke work index is lower in patients with refractory ascites. Administration of non-selective beta blockers in patients with compromised cardiac performance may increase waiting list mortality. These results highlight the prognostic value of global cardiac performance in patients with end-stage cirrhosis.

P2641Renal and cardiovascular benefits of treatment with angiotensin receptor blockers in patients with hypertension and chronic kidney disease: A systematic review and meta-analysis

Abstract Background Blood pressure (BP) control is critical in delaying the progression of chronic kidney disease (CKD), which otherwise results in an increased risk of cardiovascular morbidity and mortality. Angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors, are recommended by several guidelines as first-line treatment for patients with hypertension and CKD. Purpose We reviewed and analysed the effect of ARB treatment on BP and renal outcomes (estimated glomerular filtration rate (eGFR), serum creatinine (SCr), creatinine clearance (CrCl) or proteinuria) in patients with hypertension and CKD with or without diabetes, including large clinical trials such as RENAAL and IDNT. Methods MEDLINE, EMBASE, and BIOSIS databases were searched for literature from the earliest available date to July 2017. Randomised (parallel-group) controlled trials of ≥8 weeks assessed the impact of ARBs on systolic/diastolic BP (SBP/DBP), eGFR, SCr, CrCl or proteinuria were included in the analysis. Meta-analysis (post- versus pre-treatment) and meta-regression were conducted in R-statistical software (v3.4.1) using meta- and metafor-packages. Mean difference (MD, generic inverse variance) with 95% confidence intervals (CIs) was used to pool data for an outcome in a single forest plot. The risk of bias (quality) of included studies was assessed by the six items of the Cochrane instrument. Results Of the 165 articles assessed for eligibility, 24 studies were included in the analysis (19 evaluated ARBs as monotherapy, 4 evaluated ARBs in combination with other antihypertensives and 1 evaluated ARBs both as mono- and combination therapy). Treatment with ARBs as monotherapy for ≥8 weeks to &lt;1 year significantly reduced mean office SBP (MD, −12.60 mmHg; 95% CI, −18.53 to −6.67)/DBP (−6.52 mmHg; −11.27 to −1.77) (p&lt;0.01). BP reduction was also significant (p&lt;0.01) with ARB monotherapy for ≥1 year SBP (−14.84 mmHg; −17.82 to −11.85)/DBP (−10.27 mmHg; −12.26 to −8.27). ARBs also significantly reduced SBP/DBP when combined with other antihypertensive treatments for ≥8 weeks to &lt;1 year as well as for ≥1 year (Figure). Moreover, ARBs induced significant reductions (p&lt;0.01) in proteinuria (≥8 weeks to &lt;1 year [MD, −0.6 g/L; 95% CI, −0.93 to −0.26; ≥1 year [−0.9 g/L; −1.22 to −0.59]), but no significant changes in eGFR, CrCl or SCr levels. The beneficial effect of ARBs was maintained overtime with no significant additional impact on SBP change (estimate: 0.025; 95% CI, –0.14 to 0.19) or eGFR (estimate: 0.068; 95% CI, −0.14 to 0.28; p=0.53). The overall risk of bias was judged to be low. Effect of ARBs on blood pressure changes Conclusion Treatment with ARBs effectively and sustainably lowered BP and proteinuria with no significant change in eGFR in patients with hypertension and CKD with or without diabetes.

P2650Antihypertensive treatment with calcium channel blockers in patients with moderate or severe aortic stenosis: relationship with all-cause mortality

Abstract Background Hypertension is prevalent in patients with aortic stenosis (AS) and optimal blood pressure (BP) control is advised to reduce arterial load and avoid cardiovascular events. Whether calcium channel blockers (CCB) are safe is not known. Methods A total of 314 patients (age 65±12 y, 68% men) with moderate or severe asymptomatic AS were included. Results The prevalence of hypertension was 73.6%, and 65% took antihypertensive treatment. Patients who used a CCB (25%) (CCB+) were older, had higher clinic systolic BP, were more likely to have hypercholesterolemia and coronary artery disease (CAD), and to use a diuretic or alpha blocker compared to CCB- patients (all p&lt;0.05) (Table). During the baseline ETT, patients who used a CCB achieved a lower peak heart rate, a shorter exercise time and were more likely to have a blunted BP response compared to those who did not use a CCB (all p&lt;0.05) (Table). Event-free survival was significantly lower in CCB+ than CCB- patients (Fig) (all-cause mortality 16 [20.3%] versus 13 (5.6%); p&lt;0.001). In a multivariable Cox regression model, CCB+ was associated with a 6.8-fold increased hazard ratio (HR) for all-cause mortality (HR 6.77 95% CI 1.66–27.54, p=0.008), independent of age, gender, systolic BP, hypertension, diabetes, CAD, hypercholesterolemia and aortic valve area. Table 1. Baseline characteristics of patients CCB− (n=234) CCB+ (n=80) p Age, y 64±12 70±10 &lt;0.001 CAD, % 45 66 0.006 Hypercholesterolemia, % 62 78 0.015 Clinic systolic BP, mmHg 139±19 150±17 &lt;0.001 Left atrial diameter, cm 3.7±0.7 3.9±0.6 0.007 LV end-diastolic diameter, cm 4.5±0.7 4.8±0.6 0.002 LV mass index, g/m2.7 50±17 57±17 0.007 Aortic valve area, cm2 0.94±0.22 0.93±0.22 0.716 LV stroke work, g-m/bmp 155±46 175±69 0.046 Peak HR at baseline ETT, bmp 138±24 120±25 &lt;0.001 Blunted BP response, % 33 49 0.013 Exercise duration, min 10.1±4.5 8.3±3.7 0.001 Double Product, mmHg·bmp 1.85±0.43 2.08±0.54 &lt;0.001 Figure 1 Conclusion The use of calcium channel blockers was associated with an adverse effect on treadmill exercise and reduced survival in apparently asymptomatic patients with moderate or severe AS. Acknowledgement/Funding None

Сравнительная характеристика результатов лечения пациентов с доброкачественной гиперплазией предстательной железы в сочетании с гипогонадизмом

to compare the efficiency of monotherapy with -blockers vs combined therapy (-blockers in combination with Androgel) in patients with BPH and hypogonadism. a total of 60 men with BPH and hypogonadism, who were randomly selected from outpatient department were included in the study. All patients were divided into 2 groups (n=30). In Group 1 patients received silodosin, while in Group 2 men were prescribed to silodosin plus Androgel 1% topically. The duration of therapy was 6 months. The results of treatment were evaluated during baseline assessment and further visits every 2 months after starting therapy (total 4 time points). according to the ICEF-5 questionnaire, in the Group 2 an improvement in sexual function domain score (from 6.3 to 26.8 points) was shown. In addition, in combination group there were significant changes in PSA level (from 2.25 to 1.8 ng/ml), prostate volume (from 55.1 to 61.3 cm3), residual urine volume (from 72 to 19 ml), urine flow rate (from 13.34 to 21.1 ml/s), waist circumference (from 116 to 103.2 cm) and body mass index (from 35.4 to 27.2 kg/m2), while in monotherapy group none of these indicators significantly improved. the use of topical hormone replacement therapy in combination with -blockers in patients with BPH and concomitant hypogonadism is justified and effective in comparison with monotherapy with -blockers.

Antihypertensive treatment with calcium channel blockers in patients with moderate or severe aortic stenosis: Relationship with all-cause mortality

BackgroundHypertension is common in patients with aortic stenosis (AS) and optimal blood pressure (BP) control is advised to reduce arterial load and cardiovascular events. Whether calcium channel blockers (CCB) are safe is not known. MethodsThis was a retrospective analysis of 314 patients (age 65 ± 12 years, 68% men) with moderate or severe asymptomatic AS. Hypertension was defined from a history of hypertension, past or current antihypertensive treatment or a BP at the baseline clinic visit >140/90 mmHg. All patients underwent an exercise treadmill test (ETT) and echocardiography. ResultsThe prevalence of hypertension was 73.6%, and 65% took antihypertensive treatment. Patients who used a CCB (25%) (CCB+) were older, more likely to have hypercholesterolemia and coronary artery disease, and had higher systolic BP, stroke work, left ventricular mass compared to CCB-patients (all p < 0.05). During the baseline ETT, CCB+ patients achieved a lower peak heart rate, a shorter exercise time and were more likely to have a blunted BP response compared to CCB- patients (p < 0.05). Event-free survival was significantly lower in CCB+ than CCB- patients (all-cause mortality 16 [20.3%] versus 13 [5.6%]; p < 0.001). In a multivariable Cox regression model, CCB+ was associated with a 7-fold increased hazard ratio (HR) for all-cause mortality (HR 7.09; 95% CI 2.15–23.38, p = 0.001), independent of age, hypertension, diabetes, left ventricular ejection fraction, and aortic valve area. ConclusionThe use of CCB was associated with an adverse effect on treadmill exercise and reduced survival in asymptomatic patients with moderate or severe AS.

Deletion at 2q14.3 is associated with worse response to TNF-\u03b1 blockers in patients with rheumatoid arthritis

BackgroundStructural variations such as copy number variations (CNVs) have a functional impact on various human traits. This study profiled genome-wide CNVs in Korean patients with rheumatoid arthritis (RA) to investigate the efficacy of treatment with TNF-α blockers.MethodsA total of 357 Korean patients with RA were examined for the efficacy of TNF-α blocker treatment. Disease activity indexes were measured at baseline and 6 months after the treatment. The patients were classified as responders and non-responders based on the change in disease activity indexes according to the EULAR response criteria. CNVs in the same patients were profiled using fluorescence signal intensity data generated by a genome-wide SNP array. The association of CNVs with response to TNF-α blockers was analyzed by multivariate logistic regression accounting for genetic background and clinical factors including body mass index, gender, baseline disease activity, TNF-α blocker used, and methotrexate treatment.ResultsThe study subjects varied in their responses to TNF-α blockers and had 286 common CNVs in autosomes. We identified that the 3.8-kb deletion at 2q14.3 in 5% of the subjects was associated with response to TNF-α blockers (1.37 × 10− 5 ≤ P ≤ 4.07 × 10− 4) at a false discovery rate threshold of 5%. The deletion in the identified CNV was significantly more frequent in the non-responders than in the responders, indicating worse response to TNF-α blockers in the deletion carriers. The 3.8-kb deletion at 2q14.3 is located in an intergenic region with the binding sites of two transcription factors, MAFF and MAFK.ConclusionsThis study obtained the CNV landscape of Korean patients with RA and identified the common regional deletion associated with poor response to treatment with TNF-α blockers.

Treatment of plaque psoriasis with IL-23p19 blockers: A systematic review and meta-analysis

ObjectivesInterleukin(IL)-23 is a key cytokine in the pathogenesis of psoriasis, this meta-analysis was to analyze the efficacy and safety of IL-23p19 blockers in patients with plaque psoriasis. MethodsA systematic review of the literature was performed to collect double-blind randomized controlled trials(RCTs). The pooled relative risk(RR) with 95% confidence interval(CI) was calculated. All analyses were conducted with intention-to-treat basis. ResultsA total of 13 studies contained 5155 plaque psoriasis patients were included in our meta-analysis. The results indicated that IL-23p19 blockers had better efficacy than placebo for Psoriasis Area Severity Index score reductions from baseline of 75% or more (PASI75) (RR = 11.47, P < 0.001) and static Physician's Global Assessment score of 0 or 1(sPGA0/1) (RR = 11.32, P < 0.001). IL-23p19 blockers have similar safety with placebo about the incidence of adverse events(AEs) (RR = 1.22, P = 0.096) and serious adverse events(SAEs) (RR = 2.93, P = 0.965), but IL-23p19 blockers carried an increased incidence rate of infections (RR = 1.39, P < 0.001). While compared with adalimumab and ustekinumab, IL-23p19 blockers were more effective and had the similar tolerance. Among three IL-23p19 blockers, guselkumab was the most efficacious treatments, and risankizumab was better tolerated than the others. ConclusionThe IL-23p19 blockers have excellent efficacy and great safety in plaque psoriasis patients, but long-term safety remains to be determined.

Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study

Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and β blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and β blockers in patients with HFrEF. We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and β blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF. Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and β blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and β blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and β blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels. This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and β blockers than men, and brings into question what the true optimal medical therapy is for women versus men. European Commission.

Safety and Prognostic Impact of Early Treatment with Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients with Acute Heart Failure

Although angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been recommended for patients with heart failure, their clinical and prognostic impact in the very acute phase of acute heart failure (AHF) is unclear, mainly because data on their safety and efficacy are lacking. This study was a post hoc analysis of the REALITY-AHF trial. Patients with AHF who did not take an ACEI or ARB at admission were enrolled. Patients who received these medications within 48h of admission were categorized as the ACEI/ARB group, and all other patients were categorized as the no ACEI/ARB group. The primary endpoint was a composite of all-cause death and heart failure readmission within 1year of admission. Of the 1682 patients in the REALITY-AHF cohort, 900 were enrolled in this study, and 288 (32%) were included in the ACEI/ARB group. After propensity score matching, 152 pairs were evaluated, and no significant difference was found for in-hospital mortality, worsening renal function, or length of hospital stay. The ACEI/ARB group had significantly higher event-free survival (hazard ratio 0.51; 95% confidence interval 0.32-0.82; p = 0.006). Early initiation of ACEIs/ARBs within 48h of admission for hospitalized patients with AHF was not associated with adverse events and correlated with improved outcomes at 1year from admission.

Frequency of Utilization of Beta Blockers in Patients With Heart Failure and Depression and Their Effect on Mortality

Beta blockers reduce mortality and morbidity in patients with heart failure. Early reports linking β-blockers with depression may have limited their use in heart failure patients with co-morbid depression. Although more recent studies have challenged the association between β-blocker therapy and depression, patient and physicians remain concerned. The goal of this study is to evaluate the utilization and outcomes of β-blocker therapy in heart failure patients with depression. This is a retrospective cohort study of patients at a multicenter integrated healthcare system with a diagnosis of heart failure from 2008 to 2014. Among 6,915 patients with heart failure with left ventricular ejection fraction of <50%, 1,252 (18.1%) had a diagnosis of depression. Patients with depression were more likely to be women and had a higher prevalence of cardiovascular risk factors. Depression was associated with decreased odds of β-blocker treatment (adjusted odds ratio [OR], 0.77; 95% confidence interval [CI], 0.62 to 0.95; p = 0.016). During a mean follow-up of 2.6 years, 439 (35.1%) patients with depression died compared with 1,549 (27.4%) patients without depression. Depressed patients not treated with β-blocker had higher mortality compared with nondepressed patients (adjusted hazard ratio [HR], 1.4, 95% CI 1.09 to 1.7, p = 0.005). When treated with β-blockers, their risk of mortality was attenuated (HR 1.1, 95% CI 0.97 to 1.2, p = 0.14). In conclusion, β-blocker therapy remains underutilized in heart failure patients with depression, and its underutilization contributes to the reduced survival rate observed in this cohort.

DRUG-INDUCED NEUTRALIZING ANTIBODIES TO TNF-α BLOCKES IN PATIENTS WITH INFLAMMATORY JOINT DISEASES FOLLOWED BY 24-MONTHS

Introduction: The efficacy and safety of TNF-α blockers have been demonstrated in lot of clinical trials. The use of TNF-α blockers is associated with a significant improvement in the overall symptoms of patients with inflammatory joint diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). As a result of their use, the functions of affected joints and the quality of life of patients are improved. In recent years, it has been demonstrated that TNF-α blockers produce drug-induced neutralizing antibodies that reduce the effectiveness of these costly drugs. Objective: To investigate drug-induced neutralizing antibodies to TNF-α blockers in patients with inflammatory joint diseases followed by 24-months. Materials and Methods: 121 (56.8%) patients with PA, 50 (23.5%) patients with AS and 42 (19.7%) patients with PsA, treated with TNF-α blockers, were tested at 0, 6, 12, 24 months for drug-induced neutralizing antibodies. Detection of neutralizing antibodies to adalimumab (Humira) is performed by ELISA method, with Immundiagnostik - TNFα-Blocker-ADA, Antikorper gegen Adalimumab (Humira), Immundiagnostik AG, Stubenwald-Allee 8a, D 64625 Bensheim all requirements of the manufacturer. Determination of neutralizing antibodies to etanercept (Enbrel) were performed by ELISA method, with Immundiagnostik – TNF-α-Blocker-ADA, Antikorper gegen Etanercept (ENBREL), Immundiagnostik AG, Stubenwald-Allee 8a, D 64625 Bensheim, all requirements of the manufacturer. The SPSS v.24 statistical program was used. Results and conclusions: Drug-induced neutralizing antibodies in patients with RA, PsA, AS, treated with adalimumab, occurred in 11.5% of the patients 6th months after beginning of the treatment, at 12th months they were 17.64%, at the end of the second year 24.8 %. Patients treated with etanercept do not have proven neutralizing antibodies 6th months after beginning of the treatment, at the end of the first year they were 7.77%, at the end of the second year 9.63%. There is no significant difference between the number of males and females with drug-induced neutralizing antibodies (p=0.01). The number of patients with neutralizing antibodies to adalimumab and etanercept differ markedly in the 12th and 24th month (p=0.01). We recommend that the investigating of drug-induced neutralizing antibodies to TNF-α blockers have to be done every 12th months as a part of the routine work of rheumatologists.

Secondary atypical hemolytic uremic syndromes in the era of complement blockade

Le Clech etal. found rare variants in complement genes in only 5% of patients among a large cohort of secondary hemolytic uremic syndrome cases. The absence of genetic abnormalities does not exclude, however, the implication of complement in the pathogenesis of secondary hemolytic uremic syndrome. Prospective studies should be performed to evaluate the efficacy of complement blockers in patients with secondary atypical hemolytic uremic syndrome who do not respond to the treatment of the triggering condition.

Comparative effectiveness of ACE inhibitors and angiotensin receptor blockers in patients with prior myocardial infarction

ObjectiveAlthough ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly prescribed for patients with coronary artery disease, whether these medications are similarly effective is still a subject of intense...

Mexiletine Shortens the QT Interval in Patients With Potassium Channel-Mediated Type 2 Long QT Syndrome.

Long QT syndrome is a potentially lethal yet highly treatable cardiac channelopathy. Although β-blocker therapy is standard for most patients, concomitant therapy with sodium channel blockers, like mexiletine, is often utilized for patients with sodium channel-mediated type 3 long QT syndrome (LQT3). The potential role of sodium channel blockers in patients with potassium channel-mediated long QT syndrome (ie, LQT1 and LQT2) has not been investigated in detail. We performed a retrospective chart review on 12 patients (5 females; median age at diagnosis 14.1 years (interquartile range [IQR], 7.7-23; range, 0-59, median heart rate-corrected QT interval [QTc] at diagnosis 557 ms (IQR, 529-605) with genetically established LQT2 (10) or a combination of LQT1/LQT2 (1) or LQT2/LQT3 (1), who received mexiletine. Data were collected on symptomatic status, treatments, and breakthrough cardiac events after diagnosis and initiation of treatment. Additionally, 12-lead ECGs were collected at diagnosis, before initiation of mexiletine and following mexiletine to evaluate the drug's effect on QTc. Before diagnosis, 6 patients were symptomatic and, before initiation of mexiletine, 4 patients experienced ≥1 breakthrough cardiac event on β-blocker. Median age at first mexiletine dose was 24.3 years (IQR, 14-32.4). After mexiletine, the median QTc decreased by 65±45 ms from 547 ms (IQR, 488-558) premexiletine to 470 ms (IQR, 409-529) postmexiletine ( P=0.0005) for all patients. In 8 patients (67%), the QTc decreased by ≥ 40 ms with a mean decrease in QTc of 91 ms ( P < 0.008). For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up. Although commonly prescribed in patients with LQT3, mexiletine also shortens the QTc significantly in two-thirds of a small subset of patients with potassium channel-mediated LQT2. In patients with LQT2, pharmacological targeting of the physiological late sodium current may provide added therapeutic efficacy to β-blocker therapy.

Effects of ketofol and propofol on intubation conditions and hemodynamics without the use of neuromuscular blockers in patients undergoing tympanomastoidectomy

The effect of ketofol, a mixture of ketamine and propofol in various ratios, on hemodynamic, for intubation without the use of neuromuscular blockers, has not been elucidated in patients undergoing tympanomastoidectomy. We evaluated the effects of ketofol and propofol on intubation conditions and hemodynamic without the use of a neuromuscular blocker. The prospective randomized, double-blinded study was scheduled for tympanoplasty or mastoidectomy. The patients were divided randomly into a propofol group (Group P) and a ketofol group (Group KP). Intubation conditions, changes in hemodynamics, HR, MAP, systolic arterial pressure (SAP), and SpO2 values were recorded before induction, after induction, after intubation, and at 3-min intervals during the first 30 min, 5-min intervals for the next 30 min, and 10-min intervals after that. In the intragroup evaluation, SAP, DAP, MAP and HR values were lower in both groups compared to the baseline values. Hemodynamic values were significantly lower in Group P than in Group KP after intubation compared to baseline. DAP at 12 and 18 min, DAP and MAP at 24 min, SAP, DAP and MAP at 27 min, and SAP and MAP at 30 min after the start of the operation were significantly lower in Group P than in Group KP. The need for ephedrine and the number of patients who required ephedrine were significantly lower in Group KP than in Group P. Ketofol provided appropriate intubation conditions similar to propofol, without the use of a neuromuscular blocker, and contributed to better hemodynamic conditions in patients undergoing tympanomastoidectomy.

The role of b-blockers in the new revision of the 2018 European guidelines for the diagnosis and treatment of arterial hypertension in the patients with comorbidities

The review from the standpoint of the newest European guidelines for the diagnosis and treatment of arterial hypertension discusses the role of highly selective b-blockers and, above all, the superior member of these drugs - bisoprolol in blood pressure lowering therapy in comorbid patients with arterial hypertension. In terms of evidence-based medicine, the benefits of bisoprolol in patients with comorbid coronary heart disease, chronic heart failure, atrial fibrillation, and aortic pathology are discussed. The data on the feasibility and the possibility of including in the therapy highly selective b-adrenergic blockers in patients with chronic obstructive pulmonary disease, peripheral artery disease, diabetes and sexual dysfunction are presented