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ACE Inhibitor Benefit to Kidney and Cardiovascular Outcomes for Patients with Non-Dialysis Chronic Kidney Disease Stages 3-5: A Network Meta-Analysis of Randomised Clinical Trials.
Zhang, Y, He, D, Zhang, W, Xing, Y, Guo, Y, Wang, F, Jia, J, Yan, T, Liu, Y, Lin, S
Drugs. 2020;(8):797-811
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Abstract
BACKGROUND The advantages of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular events (CVEs) and delaying end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) is well-known. However, the efficacy and safety of these agents in non-dialysis CKD stages 3-5 patients are still a controversial issue. METHODS Two investigators (Yaru Zhang and Dandan He) independently searched and identified relevant studies from MEDLINE (from 1950 to October 2018), EMBASE (from 1970 to October 2018), and the Cochrane Library database. Randomised clinical trials in non-dialysis CKD3-5 patients treated with renin-angiotensin system (RAS) inhibitors were included. We used standard criteria (Cochrane risk of bias tool) to assess the inherent risk of bias of trials. We calculated the odds ratio (OR) and 95% confidence interval (CI) for each outcome by random-effects model. A 2-sided p value < 0.05 was considered statistically significant, and all statistical analyses were performed using STATA, version 15.0. This network meta-analysis was undertaken by the frequency model. RESULTS Forty-four randomised clinical trials with 42,319 patients were included in our network meta-analysis. ACEIs monotherapy significantly decreased the odds of kidney events (OR 0.54, 95% CI 0.41-0.73), cardiovascular events (OR 0.73, 95% CI 0.64-0.84), cardiovascular death (OR 0.73, 95% CI 0.63-0.86) and all-cause death (OR 0.77, 95% CI 0.66-0.91) when compared to placebo. According to the cumulative ranking area (SUCRA), ACEI monotherapy had the highest probabilities of their protective effects on outcomes of kidney events (SUCRA 93.3%), cardiovascular events (SUCRA 77.2%), cardiovascular death (SUCRA 86%), and all-cause death (SUCRA 94.1%), even if there were no significant differences between ACEIs and other antihypertensive drugs, including calcium channel blockers (CCBs), β-blockers and diuretics on above outcomes except for kidney events. ARB monotherapy and combination therapy of an ACEI plus an ARB showed no more advantage than CCBs, β-blockers and diuretics in all primary outcomes. In the subgroup of non-dialysis diabetic kidney disease patients, no drugs, including ACEIs or ARBs, significantly lowered the odds of cardiovascular events and all-cause death. However, ACEIs were still better than other antihypertensive drugs including ARBs in all-cause death but not ARBs in cardiovascular events according to the SUCRA. Only ARBs had significant differences in preventing the occurrence of kidney events compared with placebo (OR 0.82, 95% CI 0.72-0.95). Both ACEI/ARB monotherapy and combination therapy had higher odds of hyperkalaemia. ACEIs had 3.81 times higher odds than CCBs (95% CI 1.58-9.20), ARBs had 2.08-5.10 times higher odds than placebo and CCBs and combination therapy of an ACEI and an ARB had 4.80-24.5 times higher odds than all other treatments. Compared with placebo, CCBs and β blockers, ACEI therapy significantly increased the odds of cough (OR 2.90, 95% CI 1.76-4.77; OR 8.21, 95% CI 3.13-21.54 and OR 1.80, 95% CI 1.08-3.00). There were no statistical differences in hypotension among all comparisons except ACEIs versus placebo. CONCLUSIONS Although ACEIs increased the odds of hyperkalaemia, cough and hypotension, they were still superior to ARBs and other antihypertensive drugs and had the highest benefits for the prevention of kidney events, cardiovascular outcomes, cardiovascular death and all-cause mortality in non-dialysis CKD3-5 patients. In patients with advanced diabetic kidney disease, ACEIs were superior to ARBs in lowering risk of all-cause death but not in kidney events and cardiovascular events.
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Comparison of Percutaneous Coronary Intervention, Coronary Artery Bypass Grafting and Medical Therapy in Non-ST Elevation Acute Coronary Syndrome Patients With 3-Vessel Disease.
Jia, S, Zhang, C, Jiang, L, Xu, L, Tian, J, Zhao, X, Feng, X, Wang, D, Zhang, Y, Sun, K, et al
Circulation journal : official journal of the Japanese Circulation Society. 2020;(10):1718-1727
Abstract
BACKGROUND The aim of this study is to compare the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with 3-vessel disease (3VD) who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical therapy (MT).Methods and Results:Overall, 3,928 NSTE-ACS patients with 3VD were consecutively enrolled from April 2004 to February 2011 at Fu Wai Hospital. Patients were followed up for a median of 7.5 years, and were divided into PCI, CABG or MT groups according to their treatment. Compared with patients undergoing PCI, CABG patients had lower rates of myocardial infarction (MI), unplanned revascularization, major adverse cardiovascular and cerebrovascular events (MACCE) and a higher rate of stroke (all P<0.05). Compared with MT, PCI and CABG had lower incidences of all adverse outcomes (all P<0.05), except for a similar rate of stroke between PCI and MT. Kaplan-Meier analysis showed similar results. After adjusting for confounders, CABG was independently associated with a lower risk of cardiac death, revascularization and MACCE compared with PCI (all P<0.05). Compared with MT, PCI reduced long-term risk of death, whereas CABG reduced long-term risk of death, revascularization and MACCE events (all P<0.05). CONCLUSIONS In NSTE-ACS patients with 3VD, CABG is independently associated with a lower risk of long-term cardiac death, revascularization and MACCE compared with PCI. Patients who received MT alone had the highest risk of long-term MACCE.
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Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients.
Qin, X, Li, Y, Sun, N, Wang, H, Zhang, Y, Wang, J, Li, J, Xu, X, Liang, M, Nie, J, et al
Arteriosclerosis, thrombosis, and vascular biology. 2017;(1):166-172
Abstract
OBJECTIVE We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial). APPROACH AND RESULTS After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years. After the 3-week treatment period with enalapril alone, the systolic blood pressure-lowering effect was significantly reduced by 1.39 (95% confidence interval 0.40-2.37) and 3.25 (95% confidence interval 1.98-4.52) mm Hg, respectively, in those with baseline Hcy concentrations of 10 to 15 and ≥15 μmol/L (P for trend <0.001) as compared with those with Hcy concentration of <10 μmol/L. Similar results were observed after a 15-week treatment period with enalapril alone. After a median 4.5-year enalapril-based antihypertensive treatment period, compared with those with Hcy concentration of <10 μmol/L, the systolic blood pressure-lowering effect was still significantly reduced by 0.77 (95% confidence interval 0.01-1.53) and 1.70 (95% confidence interval 0.72-2.68) mm Hg, respectively, in those with Hcy concentrations of 10 to 15 and ≥15 μmol/L (P for trend <0.001). In addition, participants with higher baseline Hcy concentrations had persistently higher systolic blood pressure levels across the entire study treatment period. Similarly, baseline Hcy concentrations were inversely associated with diastolic blood pressure reduction during the short-term enalapril alone treatment. However, the inverse association between baseline Hcy and diastolic blood pressure reduction was attenuated and became insignificant after the long-term enalapril-based treatment period. CONCLUSIONS Elevated Hcy concentrations significantly decreased the antihypertensive effect of the short-term and long-term enalapril-based antihypertensive treatment in previously untreated hypertensive patients.
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Effects of RAS inhibitors on diabetic retinopathy: a systematic review and meta-analysis.
Wang, B, Wang, F, Zhang, Y, Zhao, SH, Zhao, WJ, Yan, SL, Wang, YG
The lancet. Diabetes & endocrinology. 2015;(4):263-74
Abstract
BACKGROUND Results of several studies have shown a possible beneficial effect of renin-angiotensin system (RAS) inhibitors on diabetic retinopathy, but the findings were contradictory. We did a systematic review and meta-analysis to assess the effect of RAS inhibitors on diabetic retinopathy. METHODS We identified relevant publications in PubMed, Embase, Cochrane Library Central Register of Controlled Trials, and abstracts from main annual meetings. Only randomised controlled trials comparing angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) monotherapy with other antihypertensive drugs or placebo in type 1 or type 2 diabetes were eligible for inclusion in the analysis. The primary outcomes were progression and regression of diabetic retinopathy in all patients and several subgroups. Risk ratios (RRs) with corresponding 95% CIs were pooled. We also did a network meta-analysis to assess the effect of different antihypertensive drugs on diabetic retinopathy by ranking order. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42013004548. FINDINGS 21 randomised clinical trials with 13,823 participants were included in the meta-analysis. RAS inhibitors were associated with reduced risk of progression (absolute risk difference -3%, 95% CI -5 to -1; pooled RR 0.87, 95% CI 0.80-0.95; p=0.002) and increased possibility of regression of diabetic retinopathy (8%, 1-16; RR 1.39, 95% CI 1.19-1.61; p=0.00002). In normotensive patients, RAS inhibitors decreased risk of diabetic retinopathy progression (0.81, 0.69-0.94; p=0.007) and increased possibility of regression (1.43, 1.14-1.79; p=0.002). In hypertensive patients, RAS inhibitors were not associated with difference in risk of progression of diabetic retinopathy (0.93, 0.79-1.10; p=0.42) or possibility of diabetic retinopathy regression (2.21, 0.92-5.31; p=0.08). ACE inhibitors were associated with reduced risk of diabetic retinopathy progression (0.84, 0.75-0.94; p=0.002) and higher possibility of disease regression (1.50, 1.20-1.86; p=0.0003). ARBs were associated with a higher possibility of diabetic retinopathy regression (1.32, 1.07-1.61; p=0.008), but had no effect on disease progression (0.92, 0.80-1.06; p=0.25). Network meta-analysis showed the association of antihypertensive drugs with risk of diabetic retinopathy progression was lowest for ACE inhibitors, followed by ARBs, β blockers, calcium channel blockers, and placebo in rank order. The association of antihypertensive drugs with possibility of diabetic retinopathy regression was highest for ACE inhibitors, followed by ARBs, placebo, and calcium channel blockers in rank order. INTERPRETATION In patients with diabetes, RAS inhibitors reduce the risk of diabetic retinopathy, and increase the possibility of diabetic retinopathy regression. ACE inhibitors might be better than ARBs for treating diabetic retinopathy, and might exert the most beneficial effect on diabetic retinopathy of all widely used antihypertensive drug classes.
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Intron-2 conversion polymorphism of the aldosterone synthase gene and the antihypertensive response to angiotensin-converting enzyme inhibitors.
Yu, H, Lin, S, Zhang, Y, Liu, G
Journal of hypertension. 2008;(2):251-6
Abstract
BACKGROUND Aldosterone controls sodium balance and intravascular volume, and thus helps regulate blood pressure. Secretion of aldosterone is mainly regulated at the level of expression of the aldosterone synthase (CYP11B2) gene. The intron-2 conversion polymorphism of CYP11B2 was suggested to lead to overexpression of the gene, and may therefore have potential to predict the blood pressure response of patients with essential hypertension to angiotensin-converting enzyme inhibitors (ACEIs). OBJECTIVE To investigate the association between the intron-2 conversion polymorphism and the blood pressure response to ACEIs in a hypertensive cohort. DESIGN AND METHODS After a 2-week, single-blind, placebo run-in period, ACEIs were administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. The intron-2 conversion polymorphism was examined by polymerase chain reaction. RESULTS The IwIw genotype was observed in 106 patients (20.8%), the IwIc genotype in 251 patients (49.3%), and the IcIc genotype in 152 patients (29.9%). After 6 weeks of treatment the reductions in diastolic blood pressure were significantly greater in patients carrying IcIc or IwIc compared with IwIw genotypes (9.2 +/- 7.2 or 9.2 +/- 7.1 versus 6.4 +/- 6.6 mmHg, respectively; analysis of variance, P = 0.001). Stepwise multiple regression analysis showed that significant predictors of diastolic blood pressure reduction at 6 weeks were baseline diastolic blood pressure (P < 0.001), intron-2 conversion genotype (P = 0.006) and sex (P = 0.030). CONCLUSIONS The intron-2 conversion polymorphism was related to the diastolic blood pressure lowering response in hypertensive patients treated with ACEIs. Interindividual variation in the efficacy of antihypertensive medications may therefore be influenced by genetic factors.
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[The effect of perindopril in treatment of early diabetic nephropathy with normal blood pressure and microalbuminuria].
Yao, B, Hu, G, Li, Y, Liao, Z, Zhang, Y
Zhonghua nei ke za zhi. 2001;(12):826-8
Abstract
OBJECTIVE To study the effect of perindopril in decreasing the urinary albumin excretion rate (AER) and protecting the renal function in normotensive early diabetic nephropathy. METHODS 52 diabetic patients with AER between 20 to 200 microg/min, were treated with dietary regimen, oral antihyperglycemic agents or/ and insulin till their fasting blood glucose (FBG) was < 7.0 mmol/L and postprandial blood glucose (PBG) < 10.0 mmol/L. They were then divided randomly into two groups. Group A was a control group (25 cases), the patients were administered with placebo, group B was a treatment group (27 cases), the patients were administered with perindopril (4 mg/day) FBG, PBG, glycosylated haemoglobin A1c (HbA1c), AER, blood pressure (MAP) and blood creatinine (Cr) were examined immediately and 3, 6, 12 and 18 months after the treatment. RESULTS In group A, AER was significantly increased after 12 and 18 months than at beginning, they were (52.3 +/- 8.6) microg/min and (60.4 +/- 9.0) microg/min vs (44.2 +/- 6.8) microg/min (P < 0.05). In group B, after being treated with perindopril, AER estimated 3, 6, 12 and 18 months later were (20.3 +/- 5.6) microg/min, (22.1 +/- 6.1) microg/min, (21.3 +/- 5.9) microg/min and (20.8 +/- 5.7) microg/min respectively, all were significantly lower those that of group A in the same period (P < 0.05) and also significantly lower than those at the beginning (P < 0.05). CONCLUSION Perindopril has good effects in decreasing AER in normotensive early diabetic nephropathy and in protecting the renal function.