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1.
Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction.
Kuno, T, Ueyama, H, Fujisaki, T, Briasouli, A, Takagi, H, Briasoulis, A
The American journal of cardiology. 2020;(8):1187-1193
Abstract
Clinical trials of renin-angiotensin-aldosterone system (RAAS) antagonists in heart failure with preserved ejection fraction (HFpEF) have suggested neutral results and treatment is focused on associated symptoms and comorbidities. MEDLINE and EMBASE were searched through October 2019 for randomized controlled studies investigating the effects of different RAAS antagonists in patients with HFpEF. The main outcomes were all-cause mortality, trial defined cardiovascular mortality, and heart failure (HF) hospitalizations. To compare different RAAS antagonists, a random-effects restricted-maximum-likelihood network meta-analysis based on a frequentist framework for indirect and mixed comparisons was used. We used p scores to rank best treatments per outcome. Our search identified 5 eligible clinical trials (PEP-CHF, perindopril; CHARM-preserved, candesartan; I-PRESERVE, irbesartan; TOPCAT, spironolactone; PARAGON-HF, sacubitril-valsartan and valsartan) enrolling a total 10,523 on RAAS antagonists and 6,259 controls. We did not identify any statistical difference in all-cause and cardiovascular mortality among RAAS antagonists and placebo. The combination of sacubitril-valsartan was associated with significantly decreased HF hospitalization risk compared with controls (odds ratio 0.73, 95% confidence interval 0.61 to 0.87) and angiotensin II receptor blockers (odds ratio 0.80, 95% confidence interval 0.71 to 0.91), without heterogeneity among studies (I2 = 0). Angiotensin receptor neprilysin inhibitor (ARNI) ranked better than other RAAS antagonists for HF hospitalizations (p value 0.9). In conclusion, RAAS antagonists do not affect mortality but the combination of sacubitril-valsartan is associated with lower HF hospitalizations in HFpEF patients.
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2.
Should we add atorvastatin to irbesartan for improving renoprotective effects in early diabetic nephropathy? A meta-analysis of randomized controlled trials.
Zuo, Y, Li, T, Lei, Z
Pharmacological research. 2019;:104286
Abstract
Angiotensin II receptor blocker has exhibited their renal protective benefits in diabetic nephropathy. This meta-analysis aimed to evaluate the effects of adding atorvastatin to irbesartan in early diabetic nephropathy. A systematic literature search was performed in PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang database until March 25, 2019. Randomized controlled trials evaluating the effects of adding atorvastatin to irbesartan in early diabetic nephropathy were eligible. Primary endpoint was urinary albumin excretion rate, serum creatinine, and blood urea nitrogen. Serum level of total cholesterol, triglyceride, fasting blood glucose, interleukin-6,and C-reactive protein (CRP) as well as blood pressure were secondary endpoints. Seventeen trials involving 1,390 patients were identified. Compared with irbesartan alone, co-administration of atorvastatin and irbesartan significantly reduced urinary albumin excretion rate (weighted mean differences [WMD] -21.22 μg/min; 95% confidence interval [CI] -26.95 to -15.50), serum creatinine (WMD -6.46 μmol/L; 95%CI -8.52 to 4.39),BUN (WMD -0.46 mmol/L; 95%CI -0.64 to -0.27), total cholesterol (WMD -1.79 mmol/L; 95%CI -2.34 to -1.23), triglyceride (WMD -0.93 mmol/L; 95%CI -1.20 to -0.67),and systolic blood pressure (WMD -2.27 mmHg; 95%CI -4.01 to -0.53), CRP (standard mean difference [SMD] 1.57; 95%CI -2.24 to -0.9), and Interleukin-6 (SMD 1.53; 95%CI -2.29 to -0.78). However, there was a significantly increased risk of nausea/vomiting (risk ratio 3.15; 95% CI 1.18-8.38) on the co-administration group. In conclusion, adding atorvastatin to irbesartan achieves additional renal protective benefits in early diabetic nephropathy patients. However, these findings should be interpreted with caution due to suboptimal methodological quality of the analyzed trials.
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3.
Blockade of the angiotensin system improves mental health domain of quality of life: A meta-analysis of randomized clinical trials.
Brownstein, DJ, Salagre, E, Köhler, C, Stubbs, B, Vian, J, Pereira, C, Chavarria, V, Karmakar, C, Turner, A, Quevedo, J, et al
The Australian and New Zealand journal of psychiatry. 2018;(1):24-38
Abstract
OBJECTIVE It is unclear whether blockade of the angiotensin system has effects on mental health. Our objective was to determine the impact of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor (AT1R) blockers on mental health domain of quality of life. STUDY DESIGN Meta-analysis of published literature. DATA SOURCES PubMed and clinicaltrials.gov databases. The last search was conducted in January 2017. STUDY SELECTION Randomized controlled trials comparing any angiotensin converting enzyme inhibitor or AT1R blocker versus placebo or non-angiotensin converting enzyme inhibitor or non-AT1R blocker were selected. Study participants were adults without any major physical symptoms. We adhered to meta-analysis reporting methods as per PRISMA and the Cochrane Collaboration. DATA SYNTHESIS Eleven studies were included in the analysis. When compared with placebo or other antihypertensive medications, AT1R blockers and angiotensin converting enzyme inhibitors were associated with improved overall quality of life (standard mean difference = 0.11, 95% confidence interval = [0.08, 0.14], p < 0.0001), positive wellbeing (standard mean difference = 0.11, 95% confidence interval = [0.05, 0.17], p < 0.0001), mental (standard mean difference = 0.15, 95% confidence interval = [0.06, 0.25], p < 0.0001), and anxiety (standard mean difference = 0.08, 95% confidence interval = [0.01, 0.16], p < 0.0001) domains of QoL. No significant difference was found for the depression domain (standard mean difference = 0.05, 95% confidence interval = [0.02, 0.12], p = 0.15). CONCLUSIONS Use of angiotensin blockers and inhibitors for the treatment of hypertension in otherwise healthy adults is associated with improved mental health domains of quality of life. Mental health quality of life was a secondary outcome in the included studies. Research specifically designed to analyse the usefulness of drugs that block the angiotensin system is necessary to properly evaluate this novel psychiatric target.
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4.
The impact of angiotensin receptor blockers on arterial stiffness: a meta-analysis.
Peng, F, Pan, H, Wang, B, Lin, J, Niu, W
Hypertension research : official journal of the Japanese Society of Hypertension. 2015;(9):613-20
Abstract
Some studies reported a protective role of angiotensin receptor blockers (ARBs) against arterial stiffness. Therefore, we performed a meta-analysis of published clinical trials to systematically assess the impact of ARBs on arterial stiffness as measured by using pulse wave velocity (PWV). Eligible articles were identified by searching PubMed, EMBASE, Cochrane, Wanfang and CNKI databanks before 31 July 2014. The data were extracted independently and in duplicate. Forty articles including 53 clinical trials qualified, including 1650 and 1659 subjects in ARB treatment and control groups, respectively. Overall reductions in carotid-femoral PWV (cfPWV) and brachial-ankle PWV (baPWV) were statistically significant, with an average of -42.52 cm s(-1) (95% CI: -81.82 to -3.21; P=0.034) and -107.08 cm s(-1) (95% CI: -133.98 to -80.18; P<0.0005), respectively, after receiving ARBs. Subgroup analysis by ARB type revealed that telmisartan (weighted mean difference or WMD=-100.82 cm s(-1); P<0.0005) and valsartan (WMD=-104.59 cm s(-1); P<0.0005) significantly reduced baPWV, but only valsartan reduced cfPWV (WMD=-65.58; P=0.030). cfPWV was significantly reduced in comparisons of ARBs with placebo (WMD=-79.65 cm s(-1); P=0.001), and baPWV was significantly reduced with calcium channel blockers (WMD=-130.74 cm s(-1); P<0.0005). There were low probabilities of publication bias. Taken together, our findings support the important role of ARB treatment in improving arterial stiffness.
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5.
Effects of telmisartan therapy on interleukin-6 and tumor necrosis factor-alpha levels: a meta-analysis of randomized controlled trials.
Takagi, H, Mizuno, Y, Yamamoto, H, Goto, SN, Umemoto, T, ,
Hypertension research : official journal of the Japanese Society of Hypertension. 2013;(4):368-73
Abstract
A recent meta-analysis of randomized head-to-head trials suggests that therapy with telmisartan, an angiotensin II receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor-gamma, may increase adiponectin levels more strongly than other ARB therapies. Therefore, telmisartan would be expected to reduce interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-α). To determine whether telmisartan reduces IL-6 or TNF-α, we performed the first meta-analysis of randomized controlled trials of telmisartan therapy. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through November 2011. Eligible studies were prospective randomized controlled trials of telmisartan vs. unrestricted control therapy reporting IL-6 or TNF-α levels as an outcome. For each study, data regarding percent changes from baseline to final IL-6 or TNF-α levels in both the telmisartan and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Nine reports of randomized trials enrolling a total of 645 patients were identified. Pooled analysis of seven and five trials demonstrated a statistically significant reduction in percent changes of IL-6 (fixed-effects SMD, -0.385; 95% CI, -0.581 to -0.189; P<0.001; P for heterogeneity=0.073) and TNF-α levels (random-effects SMD, -0.627; 95% CI, -0.945 to -0.308; P<0.001; P for heterogeneity=0.029) with telmisartan relative to control therapy, respectively. In conclusion, based on a meta-analysis of nine randomized controlled trials, telmisartan therapy is likely effective in reducing IL-6 and TNF-α levels.
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6.
Blood pressure reduction and renin-angiotensin system inhibition for prevention of congestive heart failure: a meta-analysis.
Verdecchia, P, Angeli, F, Cavallini, C, Gattobigio, R, Gentile, G, Staessen, JA, Reboldi, G
European heart journal. 2009;(6):679-88
Abstract
AIMS: It is unclear whether prevention of congestive heart failure (CHF) by drugs that inhibit the renin-angiotensin system (RAS) occurs over and beyond the reduction in blood pressure (BP) achieved by these drugs. METHODS AND RESULTS We conducted a meta-analysis of trials comparing angiotensin-converting enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), or calcium-channel blockers (CCBs), with diuretics, beta-blockers, or placebo in hypertensive or high-risk subjects without CHF at entry. Both fixed- and random-effect models were used. In trials vs. placebo, the risk of CHF was reduced by 21% with ACEIs (P = 0.007), whereas the effect of ARBs and CCBs was not significant (random-effect models). Thus, CCBs did not increase the risk of CHF. In trials vs. diuretics/beta-blockers, no differences were found between ACEIs and comparators [odds ratio (OR) 1.02; 95% confidence interval (CI) 0.84-1.24], whereas CCBs were associated with an 18% higher risk of CHF (OR 1.18; 95% CI 1.00-1.39; P = 0.048). Therefore, ACEIs were not superior to diuretics/beta-blockers for the prevention of CHF. Because heterogeneity between trials was significant, we investigated potential sources of heterogeneity by meta-regression. The risk of CHF decreased by 24% (P < 0.001) for each 5 mmHg reduction in systolic BP. The risk of CHF was 19% less with ACEIs/ARBs than CCBs (P < 0.001) and 16% less in studies without multiple risk factors required for entry (P = 0.009). CONCLUSION BP reduction is beneficial for the prevention of CHF. Over and beyond BP reduction, the protective effect of ACEIs and ARBs is greater than that of CCBs.
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7.
Angiotensin II receptor blockers and myocardial infarction: an updated analysis of randomized clinical trials.
Volpe, M, Tocci, G, Sciarretta, S, Verdecchia, P, Trimarco, B, Mancia, G
Journal of hypertension. 2009;(5):941-6
Abstract
OBJECTIVE To evaluate the effects of treatments based on angiotensin II receptor blockers (ARBs) on the risk of myocardial infarction (MI), cardiovascular and all-cause death, as compared with conventional treatment or placebo. METHODS We performed a meta-analysis of all available major international, randomized clinical trials (20 trials, n = 108 909 patients, mean age 66.5 +/- 4.1 years), published by 31 August 2008, comparing ARBs with other drugs or conventional therapies (placebo) and reporting MI incidence. RESULTS During a mean follow-up of 3.3 +/- 1.1 years, a total of 2374/53 208 and 2354/53 153 cases of MI were recorded in ARB-based groups and in comparator arms, respectively [odds ratio (OR) 95% confidence interval (CI) 1.008 (0.950-1.069)]. Risks of MI were not different when tested in different clinical conditions, including hypertension, high cardiovascular risk, stroke, coronary disease, renal disease and heart failure. No significant differences in the risk of MI between treatment with ARBs versus placebo [OR 95% CI 0.944 (0.841-1.060)], beta-blockers and diuretics [OR 95% CI 0.970 (0.804-1.170)], calcium channel blockers [OR 95% CI 1.112 (0.971-1.272)], or angiotensin-converting enzyme (ACE) inhibitors [OR 95% CI 1.008 (0.926-1.099)] were observed. Analysis of trials comparing combination therapy based on ARBs plus ACE inhibitors versus active treatments or placebo showed equivalent MI risk [OR 95% CI 0.996 (0.896-1.107)]. CONCLUSION The present meta-analysis indicates that the risk of MI is comparable with use of ARBs and other antihypertensive drugs in a wide range of clinical conditions.
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8.
Angiotensin blockade to reduce microvascular damage in diabetes mellitus.
Schmieder, RE, Martin, S, Lang, GE, Bramlage, P, Böhm, M
Deutsches Arzteblatt international. 2009;(34-35):556-62
Abstract
BACKGROUND Diabetic retinopathy and microalbuminuria are often thought of as distinct disease entities despite their common pathophysiology. Many studies have addressed the prognostic significance of these conditions and their treatment. METHODS Medline was selectively searched for articles published from 1948 to 2008 containing the terms "angiotensin," "microalbuminuria," and "retinopathy." The results were further amplified by screening the reference sections of the retrieved articles. RESULTS Diabetic retinopathy and microalbuminuria are expressions of microvascular damage. They are promoted by hypertension, hyperglycemia, dyslipidemia, and elevated levels of angiotensin II. They are treated by adjusting these risk factors to the near-normal range. In the IDNT study, angiotensin II blockade with irbesartan was found to lead to an absolute reduction of renal events by 7.4% as compared to standard treatment, and by 9.5% as compared to amlodipine. In the DIRECT study, candesartan reduced the progression of retinopathy by 13% and effected a regression by 34%. In the Steno-2 study, an intensive program of multifactorial risk reduction significantly lowered the rate of microvascular complications over a mean follow-up interval of 3.8 years (hazard ratios for different complications varying from 0.27 to 0.45). Over the longer term (13.3 years), this approach also led to a reduction of macrovascular events (HR 0.54 for mortality of all causes, 0.43 for cardiovascular mortality, and 0.41 for cardiovascular events). CONCLUSIONS Diabetic retinopathy and microalbuminuria are expressions of microvascular damage. They often appear together and point toward possible future macrovascular events. Multifactorial intervention can lessen the consequences of these pathological conditions.
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9.
Antiproteinuric response to dual blockade of the renin-angiotensin system in primary glomerulonephritis: meta-analysis and metaregression.
Catapano, F, Chiodini, P, De Nicola, L, Minutolo, R, Zamboli, P, Gallo, C, Conte, G
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2008;(3):475-85
Abstract
BACKGROUND In patients with primary glomerulonephritis (GN), antiproteinuric response to angiotensin-converting enzyme (ACE) inhibitors plus angiotensin receptor blockers (ARBs) versus either monotherapy is undefined because of the small size of studies and high heterogeneity of response. STUDY DESIGN Meta-analysis/metaregression. SETTING & POPULATION Randomized clinical trials (RCTs). SELECTION CRITERIA FOR STUDIES RCTs published from January 1996 to April 2007. Studies were excluded if information about levels of proteinuria was not available, patients had kidney disease other than primary GN, or if they had end-stage renal disease. INTERVENTION ACE inhibitor plus ARB versus monotherapy with 1 of these drug classes. OUTCOMES Absolute changes in proteinuria (primary), blood pressure, serum potassium level, and glomerular filtration rate (GFR; secondary). RESULTS We found 13 RCTs including 425 patients with primary GN with proteinuria ranging from 0.8 to 7.9 g/d of protein and age from 25 to 60 years. Combination treatment decreased proteinuria by 0.60 g/d (95% confidence interval, 0.40 to 0.80) versus ACE-inhibitor monotherapy and 0.54 g/d (95% confidence interval, 0.30 to 0.78) versus ARB monotherapy. Baseline levels of proteinuria explained most between-study variability of the antiproteinuric response to combination therapy versus monotherapies. Systolic and diastolic blood pressure, GFR, age, and diagnosis of immunoglobulin A nephropathy did not modify antiproteinuric response. ACE-inhibitor plus ARB therapy did not change GFR, whereas it increased serum potassium levels (by 0.10 mEq/L versus ACE-inhibitor and 0.19 mEq/L versus ARB therapy) and decreased blood pressure. LIMITATIONS Only published data are included. CONCLUSIONS The antiproteinuric response to ACE-inhibitor plus ARB therapy versus either monotherapy is consistently greater and strictly related to baseline proteinuria, associated with only moderate increase in serum potassium levels, and not peculiar to immunoglobulin A nephropathy.
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10.
Cardiovascular high-risk patients--treat to protect, but whom?
Zannad, F, Jakobsen, A, Heroys, J, Ralph, A, Rees, T, Shaw, M
Medscape journal of medicine. 2008;(Supp):S2
Abstract
Current guidelines for the prevention of coronary heart disease emphasize the importance of global cardiovascular risk, which requires the evaluation and treatment of multiple risk factors. Cardiovascular risk can be stratified with the Framingham algorithm, which produces a numerical score related to the presence of risk factors, such as hypertension, dyslipidemia, and smoking. However, this algorithm is not generally applicable to European countries, particularly for those countries where the risk for cardiovascular disease is low. The SCORE (Systematic COronary Risk Evaluation) project has produced risk charts that are based on cholesterol, blood pressure, and age for low-risk European countries (Belgium, France, Greece, Italy, Luxembourg, Spain, and Switzerland) and high-risk countries. Assessments of end-organ damage can provide further prognostic information, particularly in intermediate-risk patients, but the value of including additional biomarkers in risk stratification remains to be confirmed. Risk for coronary heart disease is high or very high in more than 50% of hypertensive patients. Risk appears to be underestimated in clinical practice, particularly in those patients at highest risk. Major intervention trials with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have shown that these agents reduce the risk for cardiovascular events in patients at all levels of risk, with the greatest benefits seen in those at highest risk.