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.
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.
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.