| 1st author Year of publication Reference | Aim of the study | Study design Method of BP measurement Follow-up period | Number Population (Country, KRT modality) | Primary/analysis | Results/conclusion |
|---|---|---|---|---|---|
| Agarwal, 2014 (136) | Atenolol vs Lisinopril 3x week post HD on LVMI in hypertensive HD patients with LVH | Randomised controlled study using random permuted block design Baseline ambulatory BP then home BP 12 months | 200 USA HD | Change in LVMI | This trial was terminated early due to an excess of CV events in the ACEi group (incidence rate ratio 2.36, 95% CI 1.36 to 4.23), with no difference found in primary outcome. Despite a ‘treat to target’ design with a goal home BP of ≤140/90 mmHg, in post-hoc analysis there was a slightly lower home BP (p=0.037) in the atenolol arm; on 44-hr ABPM, there was numerically lower BP in the atenolol arm (-3.6/3 mmHg). Such differences in BP, however, were probably too small to fully account for the observed differences in the secondary outcome, given the relatively small number of participants. |
| Brunelli, 2018 (30) | Effect of Midodrine on outcomes in HD patients with IDH | Retrospective cohort study In-centre BP Up to 15 months | 3,083 USA HD | ACM, CV hospitalizations | Midodrine use compared to non-use was associated with higher rates of death (adjusted incidence rate ratio 1.37, 95% CI 1.15–1.62), all-cause hospitalization: 1.31, 1.19–1.43 and CV hospitalization: 1.41, 1.17–1.71. Midodrine use tended to be associated with lower pre-dialysis SBP, lower nadir SBP, greater fall in SBP during HD, and a greater proportion of treatments affected by IDH. Included patients were not confirmed IDH suffers. |
| Chewcharat, 2022 (152) | L-carnitine vs control in HD patients with dialysis related hypotension | Meta- analysis 6-24 weeks BP method uncertain | 224 8 RCTs USA, Mexico, UK, India, Iran, Japan, Canada, Italy HD | Incidence of dialysis related hypotension | Compared to control group, L-carnitine reduced the incidence of dialysis-related hypotension among haemodialysis patients (pooled OR = 0.26, 95% CI [0.10–0.72], p = 0.01, I2 = 76.0%). Subgroup analysis on the route of supplementation revealed that only oral but not intravenous L-carnitine significantly reduced dialysis-related hypotension. The dose > 4,200 mg/week and duration of at least 12 weeks appeared to prevent dialysis-related hypotension. |
| Gou, 2022 (144) | Effects on mortality & CV of MRAs in dialysis patients vs control | Meta-analysis BP method uncertain 2 weeks – 36 months | 1,630 16 RCTs Multicentre HD & PD | ACM, CVM, LV ejection fraction, LVMI, BP, serum K+ | Pooled analysis of 8 trials (n=1205) demonstrated that MRA may significantly reduce the risk of ACM: OR 0.42 (95% CI 0.27-0.66, p<0.01). Pooled analysis of 7 trials (n=988) showed MRAs may significantly reduce CVM: OR 0.43 (CI 0.25-0.74, p<0.01). SBP was significantly decreased by MRAs (mean difference -7.4 mmHg (CI -10.6 to -4.2 mmHg, p<0.01)) as well as DBP (mean diff -4.6 mmHg (CI -9.1 to -0.1 mmHg, p=0.04)) K+: mean difference 0.06 mmol/L (CI 0.03 to 0.15, p=0.22) |
| Heerspink, 2009 (134) | Effect of lowering BP in dialysis patients | Meta-analysis BP measurement uncertain | 1,679 Multicentre 8 RCTs (7 RCT HD 1 RCT PD) | BP reduction CVM, ACM | Meta-analysis demonstrated BP lowering medication vs control reduced BP, pooled reduction in BP -4.5/-2.3 mmHg (No CIs given), was associated with lower risk of CV events, RR 0.71 (95% CI 0.44-0.92, p=0.009), reduced relative risk of ACM, RR 0.8 (CI 0.66-0.96, p=0.014) and CV mortality: 0.71 (CI 0.5-0.99, p=0.044). Two trials studied bBs, two ACEi, three ARBs and one CCBs |
| Iseki, 2013 (137) | Olmesartan vs. ‘other’ antihypertensive, not including ACEi or ARB in hypertensive haemodialysis patients | RCT Mean follow up 3.5 years Incentre BP measurements | 469 Japan HD | Composite of CVM, (non-fatal stroke or MI and coronary revasculization), all cause death | This was a ‘treat to target’ design trial and mean BP was found to be 0.9/0.0mmHg lower in the Olmesartan group than control but not significant. 28.9% of Olmesartan group and 28.6% of control group had primary composite endpoints [hazard ratio (HR) in the olmesartan group 1.00, 95% confidence interval (CI) 0.71–1.40, P = 0.99]. All-cause deaths occurred in 38 patients (16.2%) in the olmesartan group and 39 (16.7%) in the control group (HR, 0.97; 95% CI, 0.62–1.52, P = 0.91). |
| Li, 2003 (140) | Effects of Ramipril on residual renal function in PD patients | Randomised, open-label, controlled trial 12 months BP measurements uncertain | 60 Hong Kong PD | Preservation of residual renal function | Patients were randomly assigned to ramipril or no treatment. Target BP <135/80mmHg. Residual GFR declined in both groups over 12 months but it declined by 2.07 ± 1.12mL/min per 1.73m2 in the ramipril group compared to 3.00 ± 1.86 mL/min per 1.73m2 in the control group (P=0.03). The average decline in residual GFR was 0.93 mL/min per 1.73m2 (95% CI, 0.09 to 1.78 mL/min per 1.73m2) less in patients receiving ramipril than in control patients. |
| Li, 2020 (149 | Blood pressure variability (BPV) and outcomes in HD patients | Meta-analysis BP measurements mainly clinic predialysis readings but 3 studies used ABPM 0.5 to 14 years | 31,841 15 studies 8 studies North America /Europe, 7 studies from Asia HD | ACM, CVM, CV event (CHD, MU, HF or stroke) | The meta-analysis observed that increased BPV is associated with a higher risk of cardiovascular and mortality outcomes in HD patients. A 1-SD increase in systolic BP variability was associated with an 18% higher risk of ACM (HR=1.18; 95% CI1.11-1.26, I2=53.8%). The HR for CV mortality was 1.23 (95% CI 1.10-1.37, I2=7.2%). For diastolic BP variability a 1-SD increase in DBPV was associated with an 14% higher risk of ACM (HR=1.14; 95% CI 1.05-1.23, I2=0.00%). The HR for CV mortality was 1.14 (95% CI 0.94-1.38, I2=0.00%). |
| Liu, 2017 (142) | Effect of ACEi and ARBs on CV events & residual renal function in dialysis patients vs other active treatment or placebo | Meta-analysis of RCTs 1 to 3.5 years BP measurements uncertain | 1,856 11 RCTs Multicentre (4 from Japan) PD & HD | Major CV events, changes in GFR and drug related adverse events. | Effect of ACEi/ARBs on residual renal function studied in 1 HD trial and 4 PD. ACEI/ARB therapy significantly slowed the rate of decline in both residual renal function (MD 0.93 mL/min/1.73 m2, 0.38 to 1.47 mL/min/1.73 m2) and urine volume (MD 167 ml, 95% CI 21 ml to 357 ml). No significant difference was found in respect to frequency of MI, stroke, CV death and ACM. ARB therapy reduced the risk of heart failure events by 33% (RR 0.67, 95% CI 0.47 to 0. 93). No increased risk of side effects in patients receiving ACEi/ARBs. |
| Liu, 2022 (145) | Safety & efficacy of Spironolactone in patients on dialysis | Meta-analysis 2 weeks to 3 years BP measurements uncertain | 1,258 15 RCTs Multicentre 8 RCT in HD patients, 3 in PD and 2 in both | ACM, CVD, hyperkalaemia gynaecomastia | This meta-analysis found that spironolactone significantly decreased ACM (OR 0.42 (95% CI 0.28-0.62, p<0.0001)) and CVD (OR 0.54 (CI 0.45-0.85, p<0.008)). It was shown that patients on spironolactone had significantly higher potassium levels compared to controls (mean difference 0.22 mmol/L (CI 0.12 to 0.31, p<0.0001)) although the incidence of hyperkalaemia showed no significant difference between the two groups (RR 1.21 (CI 0.83-1.77, P=0.31)). Changes in BP was a secondary outcome and pooled analysis in 10 trials showed a decrease in SBP (mean difference -4.61 mmHg (CI -10.78 to 1.56 mmHg, p=0.14)) and in DBP (mean diff -0.12 mmHg (CI -3.54 to 0.27 mmHg, p=0.94)). |
| Nishioka, 2022 (153) | Review of Carnitine supplementation in people requiring dialysis | Systematic review 2-4 months | 128 3 trials | IDH | IDH RR 0.76 (0.34-1.69. Low certainty. |
| Prakash, 2004 (151) | Safety & efficacy of Midodrine in IDH | Systematic review BP measurements incentre | 117 10 studies (not all RCTs) HD Multicentre | Post-HD BP Nadir BP Symptoms Saline usage | Six studies reported improvements in symptoms, one study reported no improvements and the other three did not report on symptoms. Pooled analysis showed an increase in post BP (mean difference: +12.4/7.3 mmHg (CI 7.1-17.6/3.7-10.9)) and an increase in nadir BP (mean difference: +13.3/5.9 mmHg (CI 8.6-18/2.7-9.1)). None of the included studies used a parallel group RCT design with the majority being pre/post intervention studies (7/10) and majority were unblinded to allocation. |
| Quach, 2016 (146) | Safety & efficacy of MRAs in patients on HD or PD with or without HF | Meta-analysis 0.5 – 36 months BP measurements variable | 829 5 in HD, 4 in PD MRA vs. placebo (n=7) or SoC (n=2) Multicentre | ACM, CVM, hyperkalaemia, BP | This meta-analysis included RCT evaluating MRAs in dialysis (8 trials spironolactone, 1 trial eplerenone). Compared to controls, the RR of CVM for patients treated with MRAs was RR 0.34 (95% CI 0.15-0.75, p=0.008) and ACM: RR 0.4 (95% CI 0.23-0.69, p=0.001). Hyperkalaemia was significantly associated with MRA use, RR 3.05 (CI 1.2-7.71, p=0.04) although there was a wide range of definitions from >5 to >6.5 mm/L used. Due to differences in BP reporting methods, meta-analysis of BP could not be completed. However decreases in pre-dialysis SBP ranged from 1.7-11mmHg and from 2-5.2mmHg in control patients. In the 2 trials that reported hypotensive episodes there was no difference between MRA and placebo groups. Studies included were small and low quality. |
| Ruggenenti, 2021 (138) | Effect of Ramipril vs non RAASi on CV events in HD patients with hypertension &/or LVH | RCT Up to 42 months BP measurement incentre | 269 Italy HD | Composite CV death, MI, stroke | Patients were randomised to ramipril or non RAASi titrated to maximum tolerated dose. At comparable BP control (treat to target design trial), 16% of ramipril group and 19% non RAASi group reached primary endpoints (HR 0.93 (CI 0.52 to 1.64, p=.8)). Hypotensive episodes were more frequent in the ramipril group vs controls (41% vs 12%) |
| Shaman, 2020 (139) | Most effective & safest BP lowering agents in dialysis patients | Network meta-analysis BP measurements uncertain | 4,283 40 RCTs (32 HD, 4 PD, 4 both) Multicentre | SBP reduction | This meta-analysis showed that ACEi, βB, CCB, MRAs all lowered SBP to greater extent than placebo; MRAs -10.8 mmHg (CI -14.8 to -6.7), βB -8.7 mmHg (CI -10.9 to -6.4), CCB -4.6 mmHg (-7 to -2.2), ACEi -4.3 mmHg (-7.2 to -1.5). However ARB, αBs, renin inhibitors did not lower BP more than placebo (-6.7 mmHg, CI -14.1 to 0.7 for αB vs. placebo; -3.0 mmHg, CI -8.7 to 2.6 for ARB vs placebo). βB vs. placebo comparison provided a high confidence rating for effect estimate whereas other comparisons in this meta-analysis varied from moderate (e.g. CCB and ACEi vs. placebo; CCB and βB vs. ACEi) to low or very low confidence ratings. MRA and βB were shown to lower BP more than ACEi (MRA -6.4mmHg, CI -11.4 to -1.4; βB -4.4 mmHg, CI -7.4 to -1.3) and also ARBs, CCBs, renin inhibitors. ACEi & ARB usage was associated with increased risk of hypotension compared to control (RR 6.62, CI 1.48 to 29.54 for ACEi; RR 1.53, CI 0.94 to 2.48 for ARB). Discontinuation due to adverse effects were more likely with MRA, ACEi, ARB (RR 3.35, CI 1.32 to 8.49 for MRA; RR 1.77, CI 1.09 to 2.87 for ACEi; RR 1.57, CI 0.96 to 2.57 for ARB) No differences between classes were observed in respect to hyperkalaemia risks. However MRAs increased K 0.32 mmol/L (CI 0.15-0.49) compared to controls. |
| Suzuki, 2008 (197) | Effect of ARBs vs non-ARBs on cardiovascular disease events in HD patients with hypertension | RCT Pre-dialysis BP 36 months | 386 HD Japan | Composite of CVM, (CV death, non-fatal stroke/MI, HF, CABG, PCI) | Patients were randomly assigned to open label ARB or non ARB. ARB choice was at the discretion of prescriber. For primary end points, event free survival was significantly greater in the ARB group (P=0.001), 49% RRR (CI 0.33-0.79, p=0.002). This reduction is driven largely by fewer fatal and non-fatal HF events. BP did not differ significantly between the 2 groups at 12, 24 and 36 months. IDH developed in 38 patients on ARBs and 36 in the non ARB group (P=0.9) |
| Weir, 2015 (147) | High vs low dialysability βBs & mortality rates in HD patients over 66 years | Retrospective cohort, propensity-matched 180 days | 6,588 HD Canada | Mortality in following 180 days | Patients over 66 years old on HD who were initiated on βBs were divided into a high dialysability group ie initiated on atenolol, acebutolol or propranolol (n=3294) or a low dialysability group initiated on bisoprolol or propranolol (n= 3294) An increased relative risk of all-cause mortality of 1.4 (95% CI 1.1 to 1.8) and cardiovascular mortality of 1.2 (95% CI 1 to 1.5) was found in those receiving high vs. low dialysability βBs. |
| Zhang, 2014 (143) | Review of ACEi & ARBs for preserving residual renal function in PD patients | Open-label studies | 257 6 trials | Review to evaluate the benefits and harms of ACEis and ARBs for preserving residual kidney function in PD patients. | Small studies have shown a benefit in preserving renal function with ARBs Long-term use (≥ 12 months) of an ARB showed significant benefit of preserving residual kidney function in CAPD patients (MD 1.11 mL/min/1.73 m2, 95% CI 0.38 to 1.83), but no significant benefit when an ARB were used short-term (≤ six months). Long-term use (>12 months) of ARBs and ACEi vs other antihypertensives were associated with preserving renal function in CAPD patients and there was no significant difference between ACEi and ARBs. There was no significant difference in BP with ARBs vs other antihypertensives. |
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