Blood Pressure-lowering Agents Research Articles

8621 A Challenging Case of Preoperative Management of Pheochromocytoma Presenting With Recurrent Hypotension

Abstract Disclosure: N. Shripad: None. R. Osman: None. Introduction: Pheochromocytoma is a neuroendocrine tumor that clinically manifests due to the hypersecretion of catecholamines. Preoperative management typically involves alpha- and beta-adrenergic blockade. Patients commonly present with hypertension; however, in rare cases, patients may be hypotensive due to other comorbidities, posing a challenge to preoperative management. The following is a case of management of a pheochromocytoma with recurrent preoperative hypotension before the initiation of blood pressure-lowering agents. Case: A 47-year-old female presented to the hospital with dizziness and hypotension. The patient has a history of bilateral nephrectomy with left-sided adrenalectomy secondary to left-sided renal cell cancer and is hemodialysis-dependent. A right-sided pheochromocytoma was diagnosed a year ago on a follow-up CT scan done for monitoring renal cell cancer. The diagnosis was later confirmed with a DODATE scan and, eventually, a biopsy. Normetanephrine levels were between 581-735 pg/mL (0-88 pg/mL), with normal metanephrine levels. She denies having hyperadrenergic spells. She was started on metoprolol and doxazosin the year prior to presentation; however, she self-discontinued doxazosin after experiencing dizziness and palpitations on hemodialysis days. On admission, she was afebrile with a blood pressure of 103/66 mm Hg and a heart rate of 115 BPM. After an interdisciplinary decision was made for surgical resection, she was restarted on a lower dose of doxazosin (1 mg) and metoprolol was increased to the goal heart rate. Despite fewer hypotensive episodes on a reduced dose of doxazosin, the patient remained hypotensive on hemodialysis days. Salt tablets were started post-dialysis after clearance from nephrology, and an improvement in blood pressure was noted. She underwent a right adrenalectomy without receiving saline infusion before surgery due to concerns about volume overload. She was started on stress dose steroids due to her history of left adrenalectomy. She remained stable during and following surgery and did not require any vasopressor support. Discussion: Perioperative management of pheochromocytoma can be challenging in hypotensive patients and is poorly documented. Midodrine, an alpha-1 agonist that is typically used in dialysis-induced hypotension, is contraindicated in the setting of pheochromocytoma. We opted to manage our patient with a reduced dose of doxazosin and beta-blocker initially; however, with continued hypotensive episodes, the addition of salt tablets preoperatively on dialysis days helped to alleviate the hypotension. Although our patient did not require it, a preoperative overnight albumin infusion is a viable alternative to saline to prevent volume overload. Despite the limited literature, the patient was treated successfully through an interdisciplinary approach. Presentation: 6/3/2024

Blood pressure lowering for kidney transplant recipients: systematic review with network meta-analysis.

Hypertension affects 50-90% of kidney transplant recipients and is associated with cardiovascular disease and graft loss. We aimed to evaluate the comparative benefits and harms of blood pressure lowering agents in people with a functioning kidney transplant. We conducted a systematic review with network meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, and CENTRAL through to October 2023. RCTs evaluating blood pressure lowering agents administered for at least 2 weeks in people with a functioning kidney transplant with and without preexisting hypertension were eligible. Two reviewers independently extracted data. The primary outcome was graft loss. Treatment effects were estimated using random effects network meta-analysis, with treatment effects expressed as an odds ratio (OR) for binary outcomes and mean difference (MD) for continuous outcomes together with their 95% confidence interval (CI). Confidence in the evidence was assessed using GRADE for network meta-analysis. Ninety-four studies (7547 adults) were included. Two studies were conducted in children. No blood pressure-lowering agent reduced the risk of graft loss, withdrawal because of adverse events, death, cardiovascular or kidney outcomes compared with placebo/other drug class. Angiotensin-converting enzyme inhibitors and angiotensin receptor blocker therapy may incur greater odds of hyperkalemia compared with calcium channel blockers [odds ratio (OR) 5.48, 95% confidence interval (CI) 2.47-12.16; and OR 8.67, 95% CI 2.65-28.36; low certainty evidence, respectively). The evidentiary basis for the comparative benefits and safety of blood pressure lowering agents in people with a functioning kidney transplant is limited to guide treatment decision-making.

Influence of renin-angiotensin system blockades on vascular access survival in patients on maintenance hemodialysis.

Results on the association between the use of renin-angiotensin system blockades (RASBs) and vascular access-related outcomes are inconsistent. We aimed to compare vascular access-related outcomes according to the use of RASBs in hemodialysis patients. This study used data from a national hemodialysis quality assessment program of the Republic of Korea (n = 54,903). Group 1 was not prescribed any blood pressure-lowering drugs (n = 28,521). Group 2 was prescribed other blood pressure-lowering agents except for RASBs (n = 9571). Group 3 was prescribed RASBs (n = 16,811). Vascular access-related outcomes were classified into intervention-free survival (IFS), thrombosis-free survival (TFS), and vascular access survival (VAS). No significant difference in the three access survival rates was identified among the three groups. The multivariate Cox regression analyses indicated that Group 3 had better outcomes in IFS and TFS than Group 1. The numbers of angioplasties performed were significantly greater in Group 1 than in the other two groups. The numbers of thrombectomies performed were significantly the lowest in Group 3 among all the groups. Our study revealed different results according to types of access survival in univariate or multivariate analyses. The association of RASBs with favorable outcomes in vascular access remains unclear.

Estimation of antihypertensive effect after initiating continuous positive airway pressure treatment in Japanese patients with sleep disordered breathing

Abstract Introduction It is true that patients with cardiovascular diseases including hypertension have already suffered from sleep disordered breathing (SDB). Furthermore, Continuous Positive Airway Pressure (CPAP) treatment shows antihypertensive effect by improving sympathetic nervous activity. On the other hand, we reported that CPAP treatment had a beneficial effect on hypertension, but 70% patients still remain inadequately treated. As a result, we need the strict blood pressure follow up for patient with SDB after initiating CPAP treatment at ESC congress 2022. Purpose Our aim in this study is to estimate the antihypertensive effect after initiating CPAP treatment, also estimate the differences of CPAP effect by focusing on Japanese non-obese body. Methods All patients were conducted full night polysomnography. One-hundred eighty patients showed obstructive SDB {apnea hypopnea index (AHI) >20/hour}, and CPAP treatment were initiated. We divided into three groups by using body mass index (BMI). Group A showed BMI < 25 kg/m2 (n = 59). Group B showed 25 ≦BMI < 30 kg/m2 (n = 68), and Group C showed 30 ≦ BMI kg/m2 (n = 53). If patients had already taken blood pressure-lowering agents, they had to continue blood pressure-lowering agents without changing other agents or dose intensification. According to Japanese society of hypertension guidelines for the managements of hypertension 2019 (JSH2019), we estimated the improvement of blood pressure to assess effectiveness of CPAP treatment after six-month follow up. Results The study group consisted of 180 SDB patients (152 males, 28 females). The mean age was 53 ± 12 years. Figure 1 showed polysomnographic data before initiating CPAP treatment. Group A was significantly lower apnea hypopnea index (AHI) than in Group B and C (p < 0.0001). Figure 2 showed the changes of blood pressure after initiating CPAP treatment (six-month). There was no significant difference respect to changes of systolic blood pressure (ΔSBP), but Group A showed the tendency for worsening SBP compared with other groups. Conclusions We could estimate that CPAP treatment had only limited effects in antihypertensive effect for Japanese patients, who especially had non-obese body and lower AHI level. We need the strict blood pressure follow up for patient with SDB after initiating CPAP treatment.Figure

Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs): a multicentre, open-label, randomised, crossover trial

Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect microvascular function in people with small vessel disease. We did a multicentre, open-label, randomised crossover trial with blinded endpoint assessment at five specialist centres in Europe. We included participants aged 18 years or older with symptomatic sporadic small vessel disease or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and an indication for antihypertensive treatment. Participants were randomly assigned (1:1:1) to one of three sequences of antihypertensive treatment using a computer-generated multiblock randomisation, stratified by study site and patient group. A 2-week washout period was followed by three 4-week periods of oral monotherapy with amlodipine, losartan, or atenolol at approved doses. The primary endpoint was change in cerebrovascular reactivity (CVR) determined by blood oxygen level-dependent MRI response to hypercapnic challenge in normal-appearing white matter from the end of washout to the end of each treatment period. Efficacy analyses were done by intention-to-treat principles in all randomly assigned participants who had at least one valid assessment for the primary endpoint, and analyses were done separately for participants with sporadic small vessel disease and CADASIL. This trial is registered at ClinicalTrials.gov, NCT03082014, and EudraCT, 2016-002920-10, and is terminated. Between Feb 22, 2018, and April 28, 2022, 75 participants with sporadic small vessel disease (mean age 64·9 years [SD 9·9]) and 26 with CADASIL (53·1 years [7·0]) were enrolled and randomly assigned to treatment. 79 participants (62 with sporadic small vessel disease and 17 with CADASIL) entered the primary efficacy analysis. Change in CVR did not differ between study drugs in participants with sporadic small vessel disease (mean change in CVR 1·8 × 10-4%/mm Hg [SE 20·1; 95% CI -37·6 to 41·2] for amlodipine; 16·7 × 10-4%/mm Hg [20·0; -22·3 to 55·8] for losartan; -7·1 × 10-4%/mm Hg [19·6; -45·5 to 31·1] for atenolol; poverall=0·39) but did differ in patients with CADASIL (15·7 × 10-4%/mm Hg [SE 27·5; 95% CI -38·3 to 69·7] for amlodipine; 19·4 × 10-4%/mm Hg [27·9; -35·3 to 74·2] for losartan; -23·9 × 10-4%/mm Hg [27·5; -77·7 to 30·0] for atenolol; poverall=0·019). In patients with CADASIL, pairwise comparisons showed that CVR improved with amlodipine compared with atenolol (-39·6 × 10-4%/mm Hg [95% CI -72·5 to -6·6; p=0·019) and with losartan compared with atenolol (-43·3 × 10-4%/mm Hg [-74·3 to -12·3]; p=0·0061). No deaths occurred. Two serious adverse events were recorded, one while taking amlodipine (diarrhoea with dehydration) and one while taking atenolol (fall with fracture), neither of which was related to study drug intake. 4 weeks of treatment with amlodipine, losartan, or atenolol did not differ in their effects on cerebrovascular reactivity in people with sporadic small vessel disease but did result in differential treatment effects in patients with CADASIL. Whether antihypertensive drug classes differentially affect clinical outcomes in people with small vessel diseases requires further research. EU Horizon 2020 programme.

Blood pressure lowering effects of Vernonia amygdalina Del. Aqueous fraction on hypertensive Wistar Kyoto rats.

Vernonia amygdalina (VA) is a plant that consumed as vegetable by Indonesians contained numerous secondary metabolites. VA's pharmacological action, including its antioxidant properties, anticancer, antidiabetic, and hepatoprotective. The purpose of this research is to reveal the activity of Vernonia amygdalina. leafs aqueous fraction (VALAF) as a blood pressure-lowering agent in hypertensive model. Combination of prednisone and NaCl were used as hypertensive inducer. The animals were split into five different groups, normal control group treated with distilled water, treatment VALAF groups with dose of 10; 20 and 40 mg/kg BW respectively, while the last group was treated with captopril at dose of 2.25 mg/kg BW. All animals were given an oral treatment for 15days. On days 5, 10, and 15, systolic and diastolic blood pressure, heart rate (HR), mean arterial pressure (MAP), and blood flow (BF) were all measured. On days 0 and 15, NO level were assessed. All data were analyzed using two-way ANOVA, and Duncan Multiple Range Test. The V.amygdalina leaf aqueous fraction has blood pressure lowering activity. The blood pressure parameter of the rats treated with VALAF were lower as compared to the normal control group (p<0.05). NO levels in the VALAF group were not significantly higher than in the normal control group (p>0.05). The VALAF 20 give the greatest percentage of decrease in blood pressure, heart rate and blood volume on the 15th day of examination. These study indicated that V.amygdalina leaf aqueous fraction has the potential to be an alternative therapy for managing blood pressure in hypertensive animal models.

Bioactive properties and organosulfur compounds profiling of newly developed garlic varieties of Bangladesh

Studies are being carried out on achieving the maximum quality of garlic through various approaches. In Bangladesh, new garlic varieties (BARI 1–4, BAU-1, BAU-2, BAU-5) have been recently developed by artificial selection to enhance their quality. The present study aimed to evaluate their potency in terms of bioactive properties and organosulfur compounds content using different bioassay and GC–MS techniques while comparing them with other accessible varieties (Chinese, Indian, Local). The new variety, BARI-3 showed the highest antioxidant activity and total phenolic content. It was also found with the highest level of a potent blood pressure-lowering agent, 2-vinyl-4H-1,3-dithiine (78.15 %), which is never reported in any garlic at this percentage. However, the local variety exhibited greater inhibitory properties against the tested organisms including multidrug-resistant pathogens compared to other varieties. This study primarily shows the potential of these two kinds of garlic for their further utilization and development.

Sodium-Glucose Cotransporter-2 Inhibitors-Miracle Drugs for the Treatment of Chronic Kidney Disease Irrespective of the Diabetes Status: Lessons from the Dedicated Kidney Disease-Focused CREDENCE and DAPA-CKD Trials.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease worldwide. In Japan, the proportion of new patients requiring dialysis due to DKD has remained unchanged over the past five years. Early diagnosis and treatment are extremely important for the prevention of DKD progression. Albuminuria is the most promising biomarker currently available for diagnosing DKD and predicting its prognosis at an early stage; however, it has relatively poor specificity and sensitivity for DKD. Measuring the serum levels of tumor necrosis factor receptors (TNFRs; TNFR1 and TNFR2) is an alternative for predicting the prognosis of patients with CKD, irrespective of their diabetes status. Cardiorenal risk factor management and renin-angiotensin system inhibitor usage are effective in slowing the DKD progression, although the residual risk remains high in patients with DKD. Recently, two classes of antihyperglycemic agents, sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists, in addition to nonsteroidal selective mineralocorticoid receptor antagonists, which are less potent blood pressure-lowering and potassium-sparing agents, have emerged as cardiorenal disease-modifying therapies for preventing the DKD progression. This review focused on the SGLT2 inhibitor-based therapeutic strategies that have demonstrated cardiorenal benefits in patients with type 2 diabetes.

Real-world data in the management of hypertension for patients with sleep disordered breathing after initiating continuous positive airway pressure treatment

Abstract Introduction There are many reports that patients with cardiovascular diseases including hypertension have already suffered from sleep disordered breathing (SDB). Furthermore, Continuous Positive Airway Pressure (CPAP) is effective for hypertension for improvement of sympathetic nervous activity reason. Previously, we reported that SDB is just as, if not more, important as common classical risk factors (hypertension, dyslipidemia, diabetes mellitus) for patients with cardiovascular diseases (Figure 1). Purpose Our aim in this study is to estimate the real-world data in the management of hypertension for patients with SDB after initiating CPAP treatment. Methods All patients were conducted full night polysomnography. One-hundred ninety-five patients showed obstructive SDB {apnea hypopnea index (AHI) &amp;gt;20/hour}, and CPAP treatment were initiated. According to Japanese society of hypertension guidelines for the managements of hypertension 2019 (JSH2019), we estimated the blood pressure and presence of blood pressure-lowering agents to assess effectiveness of CPAP treatment after six-month follow up. Results The study group consisted of 195 SDB patients (166 males, 29 females). The mean age was 59±7 years. Figure 2 showed the blood pressure and presence of blood pressure-lowering agents after initiating CPAP treatment. Group A which showed systolic blood pressure (SBP) &amp;lt;130 mmHg without intake of blood pressure-lowering agents was 20.9%. Group B which showed SBP &amp;lt;130 mmHg with intake of blood pressure-lowering agents was 9.6%. Group C showed SBP≥130 mmHg without intake of blood pressure-lowering agents was 30.5%. Group D showed SBP≥130 mmHg with intake of blood pressure-lowering agents was 39.0%. Conclusion We could estimate that there were high prevalence of hypertension for patients with SDB after initiating CPAP treatment. It is true that CPAP treatment have a beneficial effect on hypertension, but 70% patients (Group C and D) still remain inadequately treated. We need the strict blood pressure follow up for patient with SDB before and after initiating CPAP treatment. Funding Acknowledgement Type of funding sources: None.

A healthy lifestyle is associated with lower arterial stiffness in a metabolically healthy elderly population with overweight or obesity.

Arterial stiffness is linked with the development of cardiovascular and noncardiovascular diseases. In clinical practice, measurement of carotid-femoral pulse wave velocity (cf-PWV) has become a widely used study for the assessment of cardiovascular risk in elderly population. Our aim was to evaluate whether maintaining a healthy life, based on Mediterranean Diet (MedDiet) and regular practice of physical activity, are associated with arterial stiffness in an elderly, metabolically healthy with overweight or obesity (MHOe) population. A transversal, analytical-descriptive study in MHOe population (aged ≥65 years) with a BMI at least 27 kg/ m 2 who had one or less of the following cardiometabolic disorders: fasting plasma glucose at least 100 mg/dl, blood pressure at least 135/85 mmHg (or the use of blood pressure-lowering agents), low high-density lipoprotein (HDL) cholesterol (≤ 40 mg/dl for men, ≤50 mg/dl for women) or triglycerides at least 150 mg/dl (or the use of lipid-lowering therapies) was conducted. Blood pressure, height, weight, BMI, waist to hip ratio (WHR), practice of physical activity, MedDiet adherence and food intake along with cf-PWV were analysed. One hundred and fifty-eight MHOe individuals (age: 72.2 ± 5.0 years, BMI: 31.6 ± 3.8 kg/m 2 ) were recruited. One hundred and nine of them were younger than 75 years of age (young-old, age: 69.3 ± 2.8 years and BMI: 32.0 ± 3.9 kg/m 2 ) and 49 of them aged 75 years or older (old-old, age: 78.1 ± 2.9 years and BMI: 30.7 ± 3.6 kg/m 2 ). All population showed a strong adherence to the Med Diet due major consumption of homemade meal, olive oil and lean meats. In addition, they presented an important practice of all intensities of physical activity. Young-old individuals had a cf-PWV of 9.7 ± 2.2 m/s and old-old individuals had a cf-PWV of 11.1 ± 4.4 m/s. In all populations, a negative correlation between cf-PWV and BMI ( r = -0.17, P = 0.04) and a positive correlation with WHR in men ( r = 0.18, P = 0.03) was found. WHR shows a significantly positive correlation with the cf-PWV values in old-old women participants ( r = 0.41, P = 0.008). On the other side, only vigorous physical activity showed a negative correlation with cf-PWV in all population and in young-old individuals ( r = -0.20; P = 0.02 and r = -0.22; P = 0.03, respectively). Healthy lifestyle habits based on MedDiet adherence and regular practice of physical activity are associated with lower arterial stiffness in a metabolically healthy population with overweight or obesity older than 65 years compared with data from other elderly populations previously reported in the literature.

Trends of medication used in patients with pre-ESKD from 2010 to 2018 in Taiwan

The burden of end-stage kidney disease (ESKD) continues to grow globally. Information on medication prescribed to advanced chronic kidney disease (CKD) patients can help formulate further CKD prevention policies. This study aimed to review and assess several major medications routinely prescribed to pre-ESKD patients. Medication information of advanced CKD patients one year before regular dialysis was collected from the National Health Insurance Research Database from 2000 to 2018 in Taiwan. Usages of major medication were comprehensively analyzed. During 2000-2018, trends in medication usage evolved gradually in the pre-ESKD population in Taiwan. The use of erythropoietin had increased (48.3% in 2000 to 71.0% in 2018) with decreased blood transfusion rate (70.9% in 2003 to 52.1% in 2018). The use of non-steroidal anti-inflammatory drugs had also dropped (43.5% in 2004 to 25.5% in 2018). These changes were more evident for patients enrolled in the pre-ESKD prevention program. The most frequently used blood pressure-lowering and glucose-lowering agents were calcium channel blockers (90.6%) and insulin (78.1%), but usage of metformin was unexpectedly high (38.4% in 2018). The most frequently used blood thinner was aspirin (49.5%), with considerably increased use of direct oral anticoagulant (16.5% in 2018). An overview of the trends of major medication usage and blood transfusion represented the continuously improving care quality in pre-ESKD patients in Taiwan. These trends were especially evident in patients enrolled in the pre-ESKD prevention program. This report also indirectly indicated the potential and long-term benefits of implementing CKD and pre-ESKD prevention programs.

Treatment with Multiple Therapeutic Classes of Medication Is Associated with Survival after Stroke

Introduction: Treatment with several therapeutic classes of medication is recommended for secondary prevention of stroke. We analyzed the associations between the number of classes of prevention medications supplied within 90 days after discharge for ischemic stroke (IS)/transient ischemic attack (TIA) and survival. Methods: This is a retrospective cohort study of adults with first-ever IS/TIA (2010–2014) from the Australian Stroke Clinical Registry individually linked with data from national pharmaceutical and Medicare claims. Exposure was the number of classes of recommended medications, i.e., blood pressure-lowering, antithrombotic, or lipid-lowering agents, supplied to patients within 90 days after discharge for IS/TIA. The longitudinal association between the number of classes of medications and survival was evaluated with Cox proportional hazards regression models using the landmark approach. A landmark date of 90 days after hospital discharge was used to separate exposure and outcome periods, and only patients who survived until this date were included. Results: Of 8,429 patients (43% female, median age 74 years, 80% IS), 607 (7%) died in the year following 90 days after discharge. Overall, 56% of patients were supplied all 3 classes of medications, 28% 2 classes of medications, 11% 1 class of medications, and 5% no class of medications. Compared to patients supplied all 3 medication classes, adjusted hazard ratios for all-cause mortality ranged from 1.43 (95% confidence interval [CI]: 1.18–1.72) in those supplied 2 medication classes to 2.04 (95% CI: 1.44–2.88) in those supplied with no medication class. Discussion/Conclusion: Treatment with all 3 classes of guideline-recommended medications within 90 days after discharge was associated with better survival. Ongoing efforts are required to ensure optimal pharmacological intervention for secondary prevention of stroke.

Assessing the physical healthcare gap among patients with severe mental illness: large real-world investigation from Italy

Background One critical barrier to the uptake of mental health programmes is the so-called physical healthcare gap, a concern raised by the unattended physical comorbidity and early mortality of persons with severe mental illness. Aims To evaluate the extension of physical healthcare gap among persons with severe mental illness under chronic drug therapies. Method A population-based cohort study was carried out, using Lombardy healthcare utilisation databases. Prevalent patients treated with blood pressure-, lipid- or glucose-lowering agents were identified in January 2017. Among these, those who were receiving care for depression, schizophrenia, bipolar disorder or personality disorder formed the study cohort. A reference cohort was randomly selected from prevalent patients treated with chronic therapies without signs of severe mental disorders, to be matched with study cohort members for gender, age and number of previous contacts with the National Health System. One-year adherence to healthcare was measured through the proportion of days covered (drug adherence), and exposure to selected recommendations (clinical control adherence). Results The 55 162 patients with severe mental illness were less likely to have high adherence to blood pressure-lowering, lipid-lowering or antidiabetic agents than the reference cohort by −24% (95% CI −26 to −22%), −10% (95% CI −14 to −6%) and −25% (95% CI −29 to −21%), respectively. The 9250 patients with diabetes and severe mental illness had −18% (95% CI −22% to −13%) reduced likelihood to meet recommendations for the clinical management of diabetes, compared with the reference cohort. Conclusions Adherence to chronic drug therapies was sensibly worse among patients living with mental illness than those without signs of mental disorders.

Cardiovascular Outcomes and Mortality Associated With Discontinuing Statins in Older Patients Receiving Polypharmacy

Polypharmacy is a major health concern among older adults. While deprescribing may reduce inappropriate medicine use, its effect on clinical end points remains uncertain. To assess the clinical implications of discontinuing the use of statins while maintaining other drugs in a cohort of older patients receiving polypharmacy. This retrospective, population-based cohort study included the 29 047 residents in the Italian Lombardy region aged 65 years or older who were receiving uninterrupted treatment with statins, blood pressure-lowering, antidiabetic, and antiplatelet agents from October 1, 2013, until January 31, 2015, with follow-up through June 30, 2018. Data were collected using the health care utilization database of Lombardy region in Italy. Data analysis was conducted from March to November 2020. Cohort members were followed up to identify those who discontinued statins. Among this group, those who maintained other therapies during the first 6 months after statin discontinuation were 1:1 propensity score matched with patients who discontinued neither statins nor other drugs. The pairs of patients discontinuing and maintaining statins were followed up from the initial discontinuation until June 30, 2018, to estimate the hazard ratios (HRs) and 95% CIs for fatal and nonfatal outcomes associated with statin discontinuation. The full cohort inclued 29 047 patients exposed to polypharmacy (mean [SD] age, 76.5 [6.5] years; 18 257 [62.9%] men). Of them, 5819 (20.0%) discontinued statins while maintaining other medications, and 4010 (68.9%) of them were matched with a comparator. In the discontinuing group, the mean (SD) age was 76.5 (6.4) years, 2405 (60.0%) were men, and 506 (12.6%) had Multisource Comorbidity Scores of 4 or 5. In the maintaining group, the mean (SD) age was 76.1 (6.3) years, 2474 (61.7%) were men, and 482 (12.0%) had multisource comorbidity scores of 4 or 5. Compared with the maintaining group, patients in the discontinuing group had increased risk of hospital admissions for heart failure (HR, 1.24; 95% CI, 1.07-1.43) and any cardiovascular outcome (HR, 1.14; 95% CI, 1.03-1.26), deaths from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.05-1.19). In this study of patients receiving polypharmacy, discontinuing statins while maintaining other drug therapies was associated with an increase in the long-term risk of fatal and nonfatal cardiovascular outcomes.

Modulation of insulin resistance by renin angiotensin system inhibitors: implications for cardiovascular prevention.

Insulin resistance (IR) and the related hyperinsulinamia play a key role in the genesis and progression of the continuum of cardiovascular (CV) disease. Thus, it is reasonable to pursue in primary and secondary CV prevention, the pharmacological strategies that are capable to interfere with the development of IR. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of IR. In particular, angiotensin II (Ang II) through the generation of reactive oxygen species, induces a low grade of inflammation, which impairs the insulin signal transduction. The angiotensin converting enzyme (ACE) inhibitors are effective not only as blood pressure-lowering agents, but also as modulators of metabolic abnormalities. Indeed, experimental evidence indicates that in animal models of IR, ACE inhibitors are capable to ameliorate the insulin sensitivity. The Ang II receptor blockers (ARBs) modulate the peroxisome proliferator-activated receptor (PPAR)-γ activity. PPARâ€"γ is a transcription factor that controls the gene expression of several key enzymes of glucose metabolism. A further mechanism that accounts for the favorable metabolic properties of ARBs is the capability to modulate the hypothalamicâ€"pituitary-adrenal (HPA) axis. The available clinical evidence is consistent with the concept that both ACE inhibitors and ARBs are able to interfere with the development of IR and its consequences like type 2 diabetes. In addition, pharmacological inhibition of the RAAS has favourable effects on dyslipidaemias, metabolic syndrome and obesity. Therefore, the pharmacological antagonism of the RAAS, nowadays, represents the first choice in the prevention of cardio-metabolic diseases.

Heart Failure Guidelines: Preserved Ejection Fraction and Comorbidities

Practice Pointers| February 01 2021 Heart Failure Guidelines: Preserved Ejection Fraction and Comorbidities Crit Care Nurse (2021) 41 (1): 80. https://doi.org/10.4037/ccn2021668 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Cite Icon Cite Get Permissions Citation Heart Failure Guidelines: Preserved Ejection Fraction and Comorbidities. Crit Care Nurse 1 February 2021; 41 (1): 80. doi: https://doi.org/10.4037/ccn2021668 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentCritical Care Nurse Search Advanced Search The new guidelines regarding the management of hypertension1 are for patients in stage C heart failure with reduced ejection fraction (HFrEF). As “clinical trials evaluating goal blood pressure reduction and optimal blood pressure–lowering agents in the setting of HFrEF and concomitant hypertension have not been done,”1 the recommendation may be considered “controversial” by some. However, “in those patients at higher risk, blood pressure lowering is associated with fewer adverse cardiovascular events.”1 Thus, my opinion is that for patients at higher risk, lowering the blood pressure to the new, lower level using diet and exercise modification in addition to medications may be beneficial and result in fewer adverse cardiovascular events. The Joint National Committee guidelines2 address hypertension in the general population and hypertension in patients with chronic kidney disease or diabetes, whereas the new guidelines address hypertension only in patients in stage C HFrEF. For patients with... You do not currently have access to this content.

Design, synthesis and antihypertensive evaluation of novel codrugs with combined angiotensin type 1 receptor antagonism and neprilysin inhibition

The multifactorial etiology of hypertension has promoted the research of blood pressure-lowering agents with multitarget actions to achieve better clinical outcomes. We describe here the discovery of novel dual-acting antihypertensive codrugs combining pharmacophores with angiotensin type 1 (AT1) receptor antagonism and neprilysin (NEP) inhibition. Specifically, the codrugs combine the AT1 antagonists losartan or its carboxylic acid active metabolite (E-3174) with selected monocarboxylic acid NEP inhibitors through a cleavable linker. The resulting codrugs exhibited high rates of in vitro conversion into the active molecules upon incubation with human/rat liver S9 fractions and in vivo conversion after oral administration in rodents. Moreover, the acute effects of one of the designed codrugs (3b) was confirmed at the doses of 10, 30 and 60 mg/kg p.o. in the spontaneous hypertensive rat (SHR) model, showing better antihypertensive response over 24 hours than the administration of an equivalent fixed-dose combination of 15 mg/kg of losartan and 14 mg/kg of the same NEP inhibitor used in 3b. The results demonstrate that the codrug approach is a plausible strategy to develop a single molecular entity with combined AT1 and NEP activities, aiming at achieving improved pharmacokinetics, efficacy and dosage convenience, as well as reduced drug-drug interaction for hypertension patients. In addition, the developability of the codrug should be comparable to the one of marketed AT1 antagonists, most of them prodrugs, but bearing only the AT1 pharmacophore.

Evaluation of thionolactones as a new type of hydrogen sulfide (H2S) donors for a blood pressure regulation

Hydrogen sulfide (H2S) is a gaseous molecule that exhibits various biological effects. For example, H2S has been recognized as a blood pressure-lowering agent. Presented in this report is a new modifiable platform for H2S supply, its preparation and H2S release kinetics from a series of structurally diversified thionolactones. Furthermore, the properties of the obtained H2S donors were evaluated in both in vitro and in vivo studies. The kinetic parameters of H2S release were determined and compared with NaHS and pyrrolidine-2-thione, a thiolactame analog, using a fluorescence detection method based on 7-azido-4-methyl-2H-chromen-2-one probe. We have shown that H2S release rates from the developed compounds are controllable through structural modifications. This study shows that both the thiono-lactone ring's size and the presence of a methyl group in the thiono-lactone ring significantly influenced the rate of H2S release. Finally, we have found a significant hypotensive response to intravenous administration of the developed donors in anesthetized rats.

Ultra-low-dose quadruple combination blood pressure–lowering therapy in patients with hypertension: The QUARTET randomized controlled trial protocol

High blood pressure is the leading cause of preventable morbidity and mortality globally. Many patients remain on single-drug treatment with poor control, although guidelines recognize that most require combination therapy for blood pressure control. Our hypothesis is that a single-pill combination of 4 blood pressure–lowering agents each at a quarter dose may provide a simple, safe, and effective blood pressure–lowering solution which may also improve long-term adherence. The Quadruple UltrA-low-dose tReaTment for hypErTension (QUARTET) double-blind, active-controlled, randomized clinical trial will examine whether ultra-low-dose quadruple combination therapy is more effective than guideline-recommended standard care in lowering blood pressure. QUARTET will enroll 650 participants with high blood pressure either on no treatment or on monotherapy. Participants will be randomized 1:1 and allocated to intervention therapy of a single pill (quadpill) containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or to control therapy of a single identical-appearing pill containing irbesartan 150 mg. In both arms, step-up therapy of open-label amlodipine 5 mg will be provided if blood pressure is >140/90 at 6 weeks. The primary outcome is the difference between groups in the change from baseline in mean unattended automated office systolic blood pressure at 12-week follow-up. The primary outcome and some secondary outcomes will be assessed at 12 weeks; there is an optional 12-month extension phase to assess longer-term efficacy and tolerability. Our secondary aims are to assess if this approach is safe, has fewer adverse effects, and has better tolerability compared to standard care control. QUARTET will therefore provide evidence for the effectiveness and safety of a new paradigm in the management of high blood pressure.

Comparative proteinuria management of different angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for normotensive patients with CKD: a Bayesian network meta-analysis.

BackgroundBoth angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are blood pressure-lowering agents, but they are also being used to control proteinuria in early chronic kidney disease (CKD) patients. However, clinically, some patients present merely proteinuria without hypertension. No guidelines pointed out how to select treatments for proteinuria in normotensive patients. Thus, we conducted a Bayesian network analysis to evaluate the relative effects of different kinds of ACEI or ARB or their combination on proteinuria and blood pressure reduction.MethodsThe protocol was registered in PROSPERO with ID CRD42017073721. A comprehensive literature database query was carried out systematically according to PICOS strategies. The primary outcome was reduction in proteinuria, and the secondary outcomes were eGFR reduction and blood pressure reduction. Random-effects pairwise and Bayesian network meta-analyses were used to estimate the effect of different regimens.ResultsA total of 14 RCTs with 1,098 patients were included in the analysis. All treatment strategies of ACEI, ARB or their combination had significantly greater efficacy in reducing proteinuria than placebo in normotensive CKD patients. The combination therapy of olmesartan+temocapril had the highest probability (22%) of being the most effective treatment to reduce proteinuria in normotensive CKD patients. Olmesartan and lisinopril ranked second (12%), and temocapril ranked third (15%) but reduced blood pressure less than placebo. For IgA nephropathy, the combination therapy of olmesartan+temocapril also had the highest probability (43%) of being the best antiproteinuric treatment, while enalapril had the highest probability (58%) of being the best antiproteinuric therapy for diabetic nephropathy.ConclusionsThe combination therapy of olmesartan plus temocapril appeared to be the most efficacious for reducing proteinuria in normotensive CKD patients and IgA nephropathy, but the clinical application should be balanced against potential harms. Temocapril can be an option when practitioners are searching for more proteinuria reduction but less blood pressure variation. In normotensive diabetic nephropathy, monotherapy with the ACEI enalapril seems to be the most efficacious intervention for reducing albuminuria. Future studies are required to give a more definitive recommendation.