Combination Of Angiotensin-converting Enzyme Inhibitor Research Articles

The Potential Role of Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers in Reducing Pneumonia Severity in Older Adults.

Background Understanding the impact of pharmacological therapy on pneumonia severity is crucial for effective clinical management. The impact of angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) on pneumonia severity remains unknown, warranting further investigation. Methodology This retrospective study examined the hospital records of inpatients (≥75 years) admitted with community-acquired pneumonia in 2021. Pneumonia severity associated with the use of pre-established ACEi and BB therapy was documented using CURB-65 (confusion, uraemia, respiratory rate, blood pressure, age ≥65 years) and pneumonia severity index (PSI) scores. Descriptive statistics and multivariable linear regression were used to analyse differences across BB therapy, ACEi therapy, their combination, or neither (control group). Results A total of 803 patient records were examined, of whom 382 (47.6%) were male and 421 (52.4%) were female. Sample sizes for each group were as follows: control (n = 492), BB only (n = 185), ACEi only (n = 68), and BB + ACEi (n = 58). Distribution of aspiration pneumonia (AP) versus non-AP for each group, respectively, was control (21.1% vs. 78.9%), BB only (9.7% vs. 90.3%), ACEi only (7.3% vs. 92.7%), and ACEi + BB (12.1% vs. 87.9%). No significant differences in PSI and CURB-65 scores were found between intervention groups even after controlling for patient characteristics and irrespective of AP or non-AP aetiology. Patients with AP had significantly higher CURB-65 (p = 0.026) and PSI scores (p = 0.044) compared to those with non-AP. Conclusions Pre-prescribed ACEi or BB therapy did not appear to be associated with differences in pneumonia severity. There were no differences in pneumonia severity scores with ACEi and BB monotherapy or combined ACEi and BB therapy.

Statins, ACE/ARBs drug use, and risk of pneumonia in hospitalized older patients: a retrospective cohort study.

The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI-Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65-0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52-0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions.

The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.

Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), direct renin inhibitors (DRIs) or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or CKD progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD. This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 2006 to May 30, 2022. Study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects. There were 208 AKI events in 2690 patients on ACEi+ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi+ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA+ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA+ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus 5 events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67). Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.

Optimal medical management in patients undergoing peripheral vascular interventions for chronic limb-threatening ischemia is associated with improved outcomes

ObjectiveOptimizing medical management and risk factor modification are underused strategies in patients with chronic limb-threatening ischemia (CLTI), despite evidence of improved outcomes. The Vascular Quality Initiative (VQI) registry is a tool to improve quality of vascular care. In this study, we used the VQI to evaluate trends in medical management in patients with CLTI undergoing peripheral vascular interventions (PVI), and the impact of changes in management on overall survival (OS), amputation-free survival (AFS), and limb salvage (LS). MethodsPatients undergoing index PVI for CLTI between 2012 and 2016, with ≥24 months of follow-up were identified from the national VQI registry. Patient details including smoking status and medication use, OS, LS, and AFS were analyzed with linear-by-linear association, t test, and logistic regression. ResultsThere were 12,370 PVI completed in 11,466 patients. There was a significant increase in infrapopliteal interventions (from 29.8% to 39.0%; P < .001) and PVI performed for tissue loss (from 59.1% to 66.5%; P < .001). The percentage of current smokers at time of PVI decreased (from 36.2% to 30.7%; P = .036). At discharge, statins were initiated in 25%, aspirin in 45%, and P2Y12 therapy in 58% of patients not receiving these medications before PVI. Over the course of follow-up, dual antiplatelet therapy (DAPT) (from 41.1% to 48.0%; P < .001), angiotensin-converting enzyme (ACE) inhibitor (from 46.2% to 51.3%; P < .001), and statin (from 70.4% to 77.5%; P < .001) use increased. Combined DAPT, ACE inhibitor and statin use increased from 33.6% to 39.6% (P ≤ .001). Significant improvement in 24-month OS and AFS was noted (OS, from 90.9% to 93.7% [P = .002]: AFS, from 81.2% to 83.1% [P = .046]), but not LS (from 89.6% to 89.0%; P = .83). Combined therapy with P2Y12 inhibitors, statins and ACE inhibitors was an independent predictor of improved OS (hazard ratio, 0.61; 95% confidence interval, 0.39-0.96; P = .034). DAPT was independent predictor of improved LS (hazard ratio, 0.83; 95% confidence interval, 0.79-0.87; P < .007). ConclusionsAntiplatelet, ACE inhibitor, and statin use increased over the study period and was associated with improved OS and AFS. LS trends did not change significantly over time, possibly owing to the inclusion of patients with a greater disease burden or inadequate medical management. Medical management, although improved, remained far from optimal and represents an area for continued development.

A Real-World Analysis of Post-Marketing Surveillance Data Assessing the Incidence of Hyperkalemia or Acute Kidney Injury in Patients on Angiotensin-Converting Enzyme Inhibitors Versus Angiotensin-Receptor Blockers

Background: The widely used Renin-angiotensin-aldosterone system inhibitor (RASI) may increase the risk of hyperkalemia and acute kidney injury (AKI). We aimed to analyze the RASI-related AKI or hyperkalemia reported in the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database to optimize patients’ treatment and provide a reference for a clinically safe and rational prescription. Methods: We obtained data in FAERS recorded from January 2004 to December 2020. Disproportionality analysis and Bayesian analysis were used in data mining to screen the suspected AKI or hyperkalemia after RASI. The time to onset, hospitalization, and prognosis of RASI-associated AKI or hyperkalemia were also investigated. Results: We identified 11,301 RASI-related adverse events (AEs) of hyperkalemia and AKI in the FAERS database; 4997 were due to Angiotensin-converting enzyme inhibitors (ACEIs), 5658 were due to angiotensin receptor blockers (ARBs), and 646 were due to the combination of ACEI and ARB. AKI was more commonly reported in patients with ARB (78.42%) than ACEI users (57.27%). Hyperkalemia cases were reported more in ACEI users (28.70%) than ARB users (14.14%). The median time to onset of RAS-associated AKI was 135.0 (17.0–620.0) days. RASI-associated hyperkalemia occurred relatively later in ACEI users, with a median onset time of 261.0 (43.0–1097.7) days, compared with that of 200.5 (52.0–636.0) days in ARB users (p &lt; 0.001). Among all AEs, 72.39% of cases received hospitalization. Death occurred in 6.3% of the renal AE cases. The elderly and heart failure were potential risk factors for death in patients who developed RASI-associated renal AEs, with an increased Odds Ratio (OR) compared with younger age (OR = 1.32) and hypertension patients (OR = 2.55). Based on the criteria of the four algorithms, the ACEI and ARB combination further increased the incidence of AKI and hyperkalemia, demonstrating the highest Reporting Odds Ratios (RORs), Proportional Reporting Ratios (PRRs) and Empirical Bayesian Geometric Average (EBGMs). Conclusions: Patients who indicated RASI for heart failure demonstrated a higher death risk when AEs occurred. ACEI combined with ARB can increase the incidence of hyperkalemia and AKI. Careful and individualized management is necessary.

Relationship between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prescribing and delirium in the ICU-A secondary analysis.

Studies suggest Angiotensin-Converting Enzyme inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) may slow the decline of memory function in individuals with mild to moderate Alzheimer's disease by regulating migroglial activation and oxidative stress within the brain's reticular activating system. Therefore, we evaluated the relationship between delirium prevalence and being prescribed ACEI and ARB in participants admitted to the intensive care units (ICU). A secondary analysis of data from two parallel pragmatic randomized controlled trials was performed. ACEI and ARB exposure was defined as being prescribed an ACEI or an ARB within six months prior to the ICU admission. The primary endpoint was the first positive delirium assessment based on Confusion Assessment Method for the ICU (CAM-ICU) for up to thirty days. A total of 4791 patients admitted to the medical, surgical, and progressive ICU and screened for eligibility for the parent studies between February 2009 and January 2015 from two level 1 trauma and one safety net hospital in a large urban academic health system were included. Delirium rates in the ICU were not significantly different among participants with no exposure to ACEI/ARB (12.6%), or exposure to ACEI (14.4%), ARB (11.8%), or ACEI and ARB in combination (15.4%) in six months prior to the ICU admission. Exposure to ACEI (OR=0.97[0.77, 1.22]), ARB (OR=0.70 [0.47, 1.05]), or both (OR=0.97 [0.33, 2.89]) in six months prior to ICU admission was not significantly associated with odds of delirium during the ICU admission after adjusting for age, gender, race, co-morbidities, and insurance status. While the impact of ACEI and ARB exposure prior to the ICU admission was not associated with the prevalence of delirium in this study, further research is needed to fully understand the impact of antihypertensive medications on delirium.

Hospitalisations Related to the Combination of ACE Inhibitors and/or Angiotensin Receptor Blockers with Diuretics and NSAIDs: A Post Hoc Analysis on the Risks Associated with Triple Whammy.

This post hoc analysis aimed to assess and characterise adverse events (AEs) related to the triple whammy (i.e., combination therapy of ACE inhibitors, ACE-I, and/or angiotensin receptor blockers, ARBs, with diuretics and non-steroidal anti-inflammatory drugs, NSAIDs) leading to emergency department (ED) visits and/or hospitalisations in the Italian setting. The MEREAFaPS database was analysed. ED visits related to co-treatment with ACE-I and/or ARBs, diuretics, and NSAIDs were considered. Information on the AE (including classification, seriousness, and outcome), suspected and concomitant drugs, and concomitant conditions was retrieved and analysed. Logistic regression was used to estimate the reporting odds ratios (RORs) of hospitalisation associated with the drugs of interest. Between 1 January 2007, and 31 December 2018, 80 patients visited the ED for AEs related to the triple whammy, and a total of 261 suspected drugs were involved. Patients were mostly Caucasian females, with a median age of 85 years, and only 9 of them had renal manifestations. In this subset, drug-drug interaction contributed to kidney injury. Most patients presented a Charlson comorbidity index of 4-5. Overall, 47 patients were hospitalised (58.75%), but no significant differences in the risk of hospitalisation were found according to demographic, clinical, or therapeutic features.

PS-R04-9: REVERSIBLE ACUTE RENAL INJURY IN MALIGNANT HYPERTENSION DURING LONG-TERM FOLLOW-UP

Background: Malignant hypertension is a disease characterized by severe hypertension and multi-organ damage. Although mortality and renal prognosis have improved with antihypertensive therapy, progression to end-stage renal disease remains a leading cause of morbidity and mortality. Case presentation: A 37-year-old man with a history of untreated hypertension and proteinuria was referred to our hospital with complaints of right paralysis. He was diagnosed with left putaminal hemorrhage and treated with conservative blood pressure reduction management. He was also complicated with severe hypertension (blood pressure 231/146 mmHg), acute renal failure (BUN 39 mg/dl, serum creatinine 4.01 mg/dl, urinary protein 2.848 g/gCre), and heart failure with preserved ejection fraction (BNP 373 pg/ml). Initial evaluation demonstrated hyperreninemia (32.6 ng/ml/hr) with hyperaldosteronism (125 pg/ml), consistent with malignant hypertension. Secondary hypertension, such as primary aldosteronism, Cushing's syndrome, pheochromocytoma, and renal artery stenosis was excluded by further examination. His renal size was mildly atrophic assessed by CT scan, suggesting a history of chronic kidney disease. At first, we gradually decreased blood pressure with antihypertensive agents except for angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blockade (ARB) so as not to induce exacerbation of renal function via glomerular ischemia. In the long-term, he was treated to achieve a tight blood pressure control to systolic blood pressure of 100–110 mmHg with the combination of ACE inhibitor, calcium channel blocker, and alpha/beta blocker. Although his clinical course showed gradual recovery of renal function, our conservative approach successfully induced renal function recovery over six months of follow-up (BUN 27 mg/dl, serum creatinine 2.26 mg/dl, urinary protein 0.154 g/gCre). Discussion: Previous reports suggest that malignant nephrosclerosis may recover slowly if the blood pressure is tightly controlled during the follow-up. From a long-term perspective, tight blood pressure control with inhibition of the renin-angiotensin-aldosterone system, which is a critical factor of the pathogenesis in malignant hypertension, may provide beneficial effects on the renal prognosis of malignant hypertension.

Possibilities of achieving target levels of arterial pressure and atherogenic lipids in patients with arterial hypertension with obesity at the outpatient stage (results of a 12-week follow-up)

The aim: To study the possibility of achieving target levels of blood pressure (BP) and atherogenic lipids’ levels in patients with arterial hypertension with abdominal obesity (AO) using combined antihypertensive and lipid‑lowering therapy against the background of recommendations for lifestyle correction at the outpatient stage.&#x0D; Materials and methods. The study involved 54 patients with AH of 2 and 3 degrees with AO of I — II degrees, who were examined in the polyclinic of the GI «L. T. Malaya Therapy National Institute of the NAMS of Ukraine». The investigated group included 30 (56 %) men and 24 (44 %) women, aged 47 to 59 years (the mean age — (50.6 ± 5.2) years). All patients underwent general clinical laboratory and instrumental examinations. After the initial examination, all patients were prescribed a three‑component fixed combination (FC) of antihypertensive drugs: an angiotensin‑converting enzyme inhibitor (ACE inhibitor) perindopril, a thiazide‑like diuretic (TPD) indapamide and a long‑acting dihydropyridine calcium channel blocker (CCB) amlodipine in optimal daily doses, considering blood pressure levels. Atorvastatin was administered as a lipid‑lowering drug in a daily dose, defined depending on the initial blood levels of low‑density lipoprotein cholesterol (LDL cholesterol). Achievement of the target levels of blood pressure and LDL‑cholesterol was assessed after 6 and 12 weeks of the study. Doses of antihypertensive drugs and atorvastatin were adjusted during the study.&#x0D; Results. It has been established that 6 weeks of treatment of AH patients with AO in outpatient settings with the use of three‑component fixed combination of antihypertensive drugs (ACE inhibitors, TPD and CCBs of the dihydropyridine series) and statins’ lipid‑lowering therapy against the background of recommendations for lifestyle correction, resulted in the achievement of the target “office” BP levels of in only 57 % of patients and target levels of LDL‑cholesterol in only 32 %. Insufficient efficacy of antihypertensive therapy in the examined patients was associated with a greater severity of obesity, increased heart rate (HR) and a higher incidence of left ventricular hypertrophy (LVH), while the low efficacy of statin therapy was primarily associated with the low therapy compliance. The addition of nebivolol, cardioselective beta‑adrenoblocker (BAB) with a vasodilatory effect, to the fixed combination of ACE inhibitors, TPD and BCC significantly increased the effectiveness of antihypertensive therapy. At the same time, intensification of statin therapy did not result in the significant increase of the frequency of achieving target levels of LDL cholesterol in the blood.&#x0D; Conclusions. The standard three‑component fixed combination of antihypertensive drugs in combination with medium‑dose statin therapy and recommendations for the normalization of lifestyle was not enough effective in a significant part of AH patients with AO at the outpatient stage, which indicates the need for timely correction of drug therapy and implementation of healthy lifestyle.&#x0D;

Cardiovascular screening prior to stem cell transplantation in the United Kingdom.

Cardiovascular screening prior to stem cell transplantation in the United Kingdom.

Endothelin type A receptor blockade attenuates aorto-caval fistula-induced heart failure in rats with angiotensin II-dependent hypertension.

Evaluation of the effect of endothelin type A (ET A ) receptor blockade on the course of volume-overload heart failure in rats with angiotensin II-dependent hypertension. Ren-2 renin transgenic rats (TGR) were used as a model of hypertension. Heart failure was induced by creating an aorto-caval fistula (ACF). Selective ET A receptor blockade was achieved by atrasentan. For comparison, other rat groups received trandolapril, an angiotensin-converting enzyme inhibitor (ACEi). Animals first underwent ACF creation and 2 weeks later the treatment with atrasentan or trandolapril, alone or combined, was applied; the follow-up period was 20 weeks. Eighteen days after creating ACF, untreated TGR began to die, and none was alive by day 79. Both atrasentan and trandolapril treatment improved the survival rate, ultimately to 56% (18 of 31 animals) and 69% (22 of 32 animals), respectively. Combined ACEi and ET A receptor blockade improved the final survival rate to 52% (17 of 33 animals). The effects of the three treatment regimens on the survival rate did not significantly differ. All three treatment regimens suppressed the development of cardiac hypertrophy and lung congestion, decreased left ventricle (LV) end-diastolic volume and LV end-diastolic pressure, and improved LV systolic contractility in ACF TGR as compared with their untreated counterparts. The treatment with ET A receptor antagonist delays the onset of decompensation of volume-overload heart failure and improves the survival rate in hypertensive TGR with ACF-induced heart failure. However, the addition of ET A receptor blockade did not enhance the beneficial effects beyond those obtained with standard treatment with ACEi alone.

The impact of the Choosing Wisely Canada campaign on the simultaneous use of angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers: interrupted time-series analysis.

Choosing Wisely is a high-profile campaign seeking to reduce the use of low-value care. We investigated the impact of a Choosing Wisely Canada recommendation against using a combination of angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for the management of hypertension, heart failure or diabetic nephropathy on population-level use of these medications in British Columbia, Canada. We identified all people (any age) who were continuously registered with BC's Medical Service Plan between 2010 and 2017 with the targeted conditions. Using prescription claims data and an interrupted time-series analysis, we estimated the number of people on combination therapy per month, the proportion of days covered (PDC) by combination therapy per month and proportion of all combination prescriptions started per month in the 2 years before and after the introduction of the recommendation on Oct. 29, 2014. Of 1 104 593 people (mean age 65 yr, standard deviation 16 yr) in our study cohort, 4.6% were exposed to combination therapy, largely prescribed by family physicians (84%). The number of people on combination therapy and the PDC were declining before the recommendation, but the proportion of combination prescriptions started in the 2 years before the recommendation was increasing. After the recommendation, we observed no statistically significant changes in any outcome. The pre-existing downward trend of the monthly number of people decelerated (16.8, 95% confidence interval [CI] 14.0 to 19.5) and the proportion of prescriptions started increased (0.13%, 95% CI 0.08% to 0.18%). The Choosing Wisely Canada recommendation against using a combination of ACE inhibitors and ARBs was not associated with reduced combination therapy use in the targeted conditions. The observed pre-existing declines in this practice questions the process of selecting recommendations, and the optimal implementation and value of Choosing Wisely campaigns without other reinforcing interventions.

Hypotensive effects of drug combinations in elderly and old patients with controlled arterial hypertension

Aim. To assess the frequency of arterial hypotension, orthostatic hypotension, low blood pressure (BP) and their clinical manifestations in the group of elderly and senile patients with a controlled course of arterial hypertension (AH), taking combinations of drugs based on an angiotensin-converting enzyme inhibitor (ACE inhibitor).Materials and methods. The study included 171 male and female residents of Krasnodar Territory with drug-controlled AH (blood pressure - BP less than 140/90 mm Hg in the background of previous antihypertensive therapy containing an ACE inhibitor perindopril), and with diseases of atherosclerotic genesis. All patients were questioned, tested for balance control, assessed for the risk of falls according to the Morse scale, hypotension in orthostasis was determined, measured office BP, carried out daily monitoring of BP with the determination of the time indices of hypotension and low BP.Results. Most often patients took a combination of ACE inhibitors with calcium channel blockers (CCB) (28.1% of cases), beta-blockers (BB) (27.1%) or diuretics (29.1%). Assessing the risk of falls on the Morse scale, there was a significantly lower level in patients who took the combination of perindopril with CCB compared with those who received perindopril with BB (15 versus 25 points respectively, p=0.039). Patients receiving perindopril and CCB lost balance in the “legs together” position in 19.3% and in the “tandem” or “semi-tandem” position of the feet in 29.8% of cases, that could be compared to the group taking perindopril and a diuretic (22% and 33.9%, respectively) and significantly lower than in the groups with perindopril and BB therapy (34.5% and 50.9%, respectively, p1=0.037, p2=0.043). The time index of low systolic and diastolic BP during therapy with perindopril and CCB was significantly lower than the corresponding indicator in the groups of patients treated with perindopril and BB (22% and 17% versus 27% and 21%, respectively, p1=0,009, p2=0,024), and the time index of low systolic BP for the combination of perindopril and diuretic is lower than for the combination of perindopril and BB (23% versus 27%, respectively, p=0.023).Conclusion. The data obtained on the frequency of arterial hypotension, orthostatic hypotension and low BP in the group of elderly and senile patients indicate the advisability of further studying the risks of drug hypotension in order to better personalize the treatment of AH.

Consumption analysis of two-component fixed combinations of medicines for arterial hypertension treatment in Ukraine as one of the stages for evaluation of their reimbursement prospects

The aim was to conduct a retrospective consumption analysis of 4 groups of single pill combinations for hypertension treatment and identify potential candidates for future inclusion in the reimbursement list in Ukraine, based on retrospective consumption patterns.&#x0D; Materials and methods: The objects of the study were retail sales data in pharmaceutical market in Ukraine of four groups of single pill combinations used for arterial hypertension treatment. Data was provided by the marker research system “Pharmstandard” of the company of “Morion”. Analytic-comparative, systematic, logical, and mathematical-statistical methods were used.&#x0D; Results: Single pill combinations of ACE inhibitors with diuretics were the most consumed among other combinations on 2018-2020. Retrospective evaluation of consumption patterns in period of 2018-2020 showed that combinations of captopril and hydrochlorothiazide (HCTD) 50 mg/25 mg, enalapril and HCTD 10 mg/25 mg, lisinopril and HCTD 10 mg/12.5 mg were the most consumed. Among ARB and diuretics combinations valsartan and HTCD (160 mg/12.5 mg and 80 mg/12.5 mg) and losartan and HTCD (50 mg /12.5 mg) were the most consumed among ARB and diuretics combinations. Within ACE inhibitors and calcium channel blockers (CCB) combinations the most consumed were lisinopril/amlodipine 10 mg/5 mg and a perindopril arginine/amlodipine 5 mg/5 mg. Valsartan and amlodipine holds the majority among ARC and CCB combinations, consumed in period of 2018-2020.&#x0D; Conclusion: Apart from the single pill combinations, enlisted in the WHO Essential medicines list, eight more single pill combination were identified, based on retrospective consumption patterns, as potential candidates for further inclusion in the reimbursement list in Ukraine

Population aspects of arterial hypertension therapy. Focus on fixed combinations

High blood pressure (BP) remains the leading risk factor for coronary heart disease, stroke, other cardiovascular diseases, chronic kidney disease, and dementia. Objective. To estimate the frequency of prescribing antihypertensive drugs (AHD) with the allocation of the proportion of fixed combinations (FC) among people aged 25–64 years examined in 16 regions of the Russian Federation as part of the ESSE-RF and ESSE-RF2 studies.Design and methods. The analysis included the results of a survey of representative samples of the population of the Russian Federation in the ESSE-RF studies (2012–2014, men: N = 8376 and women N = 13546 people) and ESSE-RF2 (2017, men: N = 3000 and women N = 3714 people). Each participant signed an informed consent. Arterial hypertension (AH) was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg and/or if the examined reported taking AHD. Under the lack of control of AH, we understood the proportion of patients (%) with BP levels ≥ 140/90 mm Hg of the total number of patients with AH. Information about the AHD taken was recorded from the words of the patient (trade name of the drug) followed by coding according to the International Nonproprietary Names of Drugs.Results. In the Russian population, there was a decrease in the proportion of uncontrolled BP from 78,5 % (95 % confidence interval (CI) 77,7–79,3) in ESSE-RF to 73,0% (95 % CI 71,3–74,6) in ESSE-RF2. FC intake was detected in 15,6 % (95 % CI 13,8–18,0) of patients treated in the ESSE-RF study, while the proportion of such patients in the ESSE-RF2 decreased to 10,9% (95% CI 9,2–12,8), p &lt; 0,001. The most common FC was the combination of an angiotensin-converting enzyme inhibitors (ACEI) and a diuretic (ESSE-RF: 49,1 % and ESSE-RF2: 45,9 %). In second place in ESSE-RF is a diuretic + angiotensin receptor blockers (25,8 %), in ESSE-RF2 — calcium channel blockers (CCB) + ACEI (22,4%). A more modern combination, namely: the combination of ACEI and CCB, was noted only in 8,7% in ESSE-RF, while in ESSE-RF2 the proportion of this FC increased by 2,5 times.Conclusions. In the population of the Russian Federation, only 10 %-15 % of patients with AH receive FC AHD. An increase in FC intake may contribute to an increase in adherence to therapy, which is extremely important for the Russian population with poor BP control.

Dogs with leishmaniosis: how are we managing proteinuria in daily practice? A Portuguese questionnaire-based study

BackgroundProteinuria is a common finding in dogs with leishmaniosis. Although antileishmanial therapeutic protocols are widely implemented, little information is available on which treatments are most adequate for identifying proteinuria in patients with canine leishmaniosis (CanL), especially regarding the use of immunosuppressants. The aim of this study was to explore the current paradigm regarding the antiproteinuric approach adopted by veterinary practitioners in Portugal to treat dogs with CanL.MethodsA questionnaire-based study was developed using Google Forms®. The questionnaire presented a number of different hypothetical scenarios of CanL, and the topics surveyed included the general features of the respondents and the protocols preferred by these respondents to manage proteinuria in the presented scenarios, including choice of therapeutic drugs, appropriate diet and use of immunosuppressants, in dogs with immune-mediated glomerulonephritis. The questionnaire was internally prevalidated and diffused online over a 2-month period through Portuguese veterinary social networking groups, and data were collected for descriptive analysis.ResultsA total of 86 veterinary practitioners responded to the survey. When exposed to theoretical scenarios of proteinuria in dogs with CanL at stages IIb, III and IV (LeishVet guidelines), 16.3%, 62.8% and 93.8% of the respondents, respectively, answered that they would treat it. The dog was started on a renal diet as therapy by 28.6%, 83.3% and 97.4% of respondents, respectively. Angiotensin-converting enzyme inhibitors (ACEI) were prescribed by 100%, 85.2% and 78.9% of respondents as first-choice drugs for CanL at stages IIb, III and IV, respectively, with ACEI used in monotherapy by 64.3%, 40.7% and 46.1%. In comparison, protocols using ACEI in combination with other compounds were chosen by 7.1%, 33.3% and 39.5% of respondents, and combination therapy which did not include ACEI was the choice of 0.0%, 12.9% and 14.5%. Regarding immunosuppressants, 44.2% of the respondents answered they would prescribe them, with 97.4% electing for prednisolone and 5.3% choosing mycophenolate mofetil.ConclusionsAmong the veterinary practitioners who responded, proteinuria treatment was considered since stage IIb CanL, although implementation of a therapeutic approach was more evident in advanced CanL stages. ACEI were the first-choice drugs, particularly for the treatment of stage IIb CanL; in advanced stages, a combination of antiproteinuric drugs was more often used. Immunosuppressant use was controversial, although when applied, prednisolone was the preferred choice. These findings reinforce the small body of evidence that supports the use of such drugs and the need to further explore their role in CanL.Graphical

Efficacy of Single-Pill, Triple Antihypertensive Therapy in Patients with Uncontrolled Hypertension: A Systematic Review and Meta-analysis.

Systemic arterial hypertension is the most common preventable risk factor for all causes of morbidity and mortality worldwide with a prevalence of 35-40% of the adults. Despite the wide variety of effective antihypertensive medications, most hypertensive patients remain uncontrolled. However, the combination of ACE inhibitor, diuretics, and calcium antagonist for the triple therapy in a single Pill Combination (SPC) is an efficient regimen in hypertension management. It is recommended by the ESH 2018 guideline, which offers better efficacy and compliance to treatment. To evaluate the efficacy of perindopril/indapamide/amlodipine single-pill combination in patients with uncontrolled hypertension. We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL for relevant clinical trials. We conducted the risk of bias assessment using Cochrane's risk of bias tool. We performed the analysis of continuous data using mean difference (MD) and relative 95% confidence interval (CI), while dichotomous data were analyzed using risk ratio (RR) and relative 95% CI. We included the analysis of the following outcomes: systolic blood pressure (SBP), Diastolic blood pressure (DBP), Heart rate (HR), 24 h Ambulatory blood pressure monitoring (ABPM) for SBP, and 24 h ABPM for DBP. We included six clinical trials. We found that the triple therapy significantly reduces SBP by 24 mmHg (MD = - 24.65 [22.41, 26.89], (P < 0.01)), DBP by 12 mmHg (MD = 12.41 [11.53, 13.29], (P < 0.01)), 24-h ABPM for SBP by 14 mmHg (MD = 14.08 [9.10, 19.05], (P < 0.01)), and ABPM 24 h DBP by 7 mmHg (MD = 7.01 [5.37, 8.65], (P < 0.01)). We noted no significant difference of the single pill on heart rate (MD = 0.81 [- 0.04, 1.67], (P = 0.06). perindopril/indapamide/amlodipine is effective in reducing systolic and diastolic blood pressures by 24 and 12 mmHg respectively. Over 24 h, the combination reduced systolic and diastolic blood pressures by 14 and 7 mmHg respectively.

Efficacy and safety of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers in diabetic nephropathy: a systematic review and meta-analysis.

Diabetic nephropathy (DN) is one of the most typical microangiopathies caused by diabetes. It often leads enormous physiological and psychological burdens for patients and seriously affects their quality of life. Therefore, effective combination therapy is necessary for these patients. In this study, we performed a meta-analysis to systematically evaluate and discuss the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in the treatment of DN. The PubMed, Embase, Web of Science, and Medline databases were selected as the sources of the literature search, and the search was limited to studies published in English. Studies related to ACEIs and ARBs in the treatment of DN published from January 2001 to January 2021 were included in this analysis. Meta-analysis was performed to calculate the reinforcement mean difference. In total, eight articles involving 1,893 cases with DN were included in this study. The results of this systematic review and meta-analysis showed that for patients with diabetic nephropathy，there were significant differences in 24-hour proteinuria [mean difference (MD) =-78.46, 95% confidence interval (95% CI): -80.25 to -76.66, P<0.00001], systolic blood pressure (MD =-9.11, 95% CI: -13.44 to -4.78, P<0.0001), and diastolic blood pressure (MD =-3.39, 95% CI: -5.68 to -1.11, P=0.004) between the combined ACEI and ARB group and the single ACEI or ARB group (P<0.05). In terms of safety, in addition to the significant difference in serum potassium (MD =0.1, 95% CI: 0.05 to 0.15, P=0.0001) between the combined ACEI and ARB group and the single drug group (P<0.1), there were no notable differences in serum creatinine (MD =0.66, 95% CI: -8.0 to 2.12, P=0.37), creatinine clearance (MD =-0.25, 95% CI: -0.62, 0.11, P=0.17), or the incidence of adverse reactions [odds ratio (OR) =1.19, 95% CI: 0.81 to 1.75, P=0.37]. A total of eight studies were included in this meta-analysis. The results showed that for patients with diabetic nephropathy, the combination of ACEI and ARB was more effective than ACEI or ARB alone, and also had higher safety.

Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitors in Combination with Angiotensin-Receptor Blockers in Nondiabetic Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

It is unclear whether angiotensin-converting enzyme inhibitors (ACEIs) in combination with angiotensin-receptor blockers (ARBs) are superior to ACEIs or ARBs alone in the treatment of nondiabetic chronic kidney disease (CKD). The present meta-analysis was designed to assess the efficacy and safety of ACEIs in combination with ARBs in nondiabetic CKD. The PubMed, Embase, and Cochrane Library databases were searched to identify randomized controlled trials (RCTs) published prior to March 2020. A random-effects model was used to calculate the effect sizes of eligible studies. The present meta-analysis of 20 RCTs encompassing 1,398 patients with nondiabetic CKD demonstrated that ACEIs in combination with ARBs were superior to ACEIs or ARBs alone in reducing urine albumin excretion (SMD, -0.69; 95% CI, -1.13 to -0.25; P=0.002), urine protein excretion (SMD, -0.34; 95% CI, -0.46 to -0.23; P<0.001), and blood pressure (systolic blood pressure: WMD, -1.43; 95% CI, -2.42 to -0.44; P=0.005; diastolic blood pressure: WMD, -1.85; 95% CI, -2.67 to -1.04; P<0.001) without decreasing glomerular filtration rate (SMD, -0.07; 95% CI, -0.20 to 0.06; P=0.30) or increasing incidences of hyperkalaemia (RR, 1.70; 95% CI, 0.47 to 6.11; P=0.42) and hypotension (RR, 1.80; 95% CI, 0.67 to 4.86; P=0.25). Compared with ACEIs or ARBs alone, ACEIs in combination with ARBs are effective and safe in the treatment of nondiabetic CKD. ACEIs combined with ARBs may be a better choice to reduce proteinuria as long as they can be tolerated.

Concomitant Treatment of Hypertensive Patients with Bisoprolol and Perindopril in Routine Clinical Practice: A Post Hoc Analysis of the CONFIDENCEII, PROTECTI, and PROTECTIII Observational Studies.

IntroductionThe combination of angiotensin-converting enzyme inhibitors and beta-blockers is recommended in a wide range of patients with hypertension, including those with stable coronary artery disease and/or elevated heart rate. This post hoc analysis of three observational studies provides effectiveness and safety data on treatment with perindopril on top of bisoprolol-based therapy, in routine clinical practice.MethodsData were analyzed from three open-label, prospective, multicenter, observational studies of Canadian patients with mild-to-moderate hypertension, which shared the same inclusion and exclusion criteria, treatment duration, and primary outcome. This post hoc analysis focused on the subpopulation of patients treated with perindopril on top of bisoprolol-based therapy. All patients were followed for 16 weeks and underwent baseline, week 4, and week 16 visits. Primary outcomes were mean changes in blood pressure (BP) and proportion of patients achieving BP control (< 140/90 mmHg) in the full analysis set (FAS).ResultsA total of 845 patients (mean age 68.3 ± 11.3 years, mean baseline BP 151.5/86.0 mmHg) were analyzed in the FAS. After 16 weeks, mean SBP/DBP decreased by − 20.4/− 9.8 mmHg with statistically significant reductions observed at all visits in all three studies allowing 78% of patients to achieve the BP treatment goal. No statistically significant changes in heart rate were observed and no serious adverse events reported. The most frequent doses of bisoprolol and perindopril were 5 + 4 mg (34.9%), followed by 5 + 8 mg (16.9%), and 2.5 + 4 mg (12.5%).ConclusionThe addition of perindopril on top of bisoprolol-based therapy in patients with mild-to-moderate hypertension was associated with significant reductions in BP compared with baseline and with achievement of BP targets in the majority of patients. The results suggest this strategy is safe and effective for use in routine clinical practice.