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Efficacy and safety of dual vs single renin-angiotensin-aldosterone system blockade in chronic kidney disease: An updated meta-analysis of randomized controlled trials.
Zhao, M, Qu, H, Wang, R, Yu, Y, Chang, M, Ma, S, Zhang, H, Wang, Y, Zhang, Y
Medicine. 2021;(35):e26544
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Abstract
BACKGROUND To lower albuminuria and to achieve blood pressure (BP) goals, dual renin-angiotensin-aldosterone system (RAAS) inhibitors are sometimes used in clinical practice for the treatment of CKD. However, the efficacy and safety of dual RAAS blockade therapy remains controversial. METHODS PubMed, EMBASE, and Cochrane Library were searched, and random effects model was used to calculate the effect sizes of eligible studies. Potential sources of heterogeneity were detected by meta-regression and subgroup analysis. RESULTS The present meta-analysis of 72 randomized controlled trials with 10,296 patients demonstrated that dual RAAS blockade therapy was superior to monotherapy in reducing the urine albumin excretion, urine protein excretion, and BP. These beneficial effects were related to the decrease of glomerular filtration rate, the increase of serum potassium level, and higher rates of hyperkalemia and hypotension. Meanwhile, these effects did not lead to improvements in short-term or long-term outcomes, including doubling of serum creatinine, acute kidney injury, end-stage renal disease, mortality, and hospitalization. Compared with the single therapy, angiotensin-converting enzyme inhibitor (ACEI) in combination with angiotensin-receptor blocker (ARB) was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist in decreasing urine albumin excretion, urine protein excretion and BP, and the combination was not associated with a lower glomerular filtration rate. CONCLUSION Compared with the single therapy, ACEI in combination with ARB was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist. Although ACEI in combination with ARB was associated with higher incidences of hyperkalemia and hypotension, careful individualized management and potassium binders may further expand its application (PROSPERO number CRD42020179398).
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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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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.