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Meta-Analysis
. 2024 Oct 15;10(10):CD008564.
doi: 10.1002/14651858.CD008564.pub3.

Blood pressure targets for hypertension in people with chronic renal disease

Juan Erviti  1   2   3 , Luis Carlos Saiz  1   2 , Leire Leache  1   2 , José I Pijoan  4   5   6 , Miguel Menéndez Orenga  5   7 , Douglas M Salzwedel  8 , Iván Méndez-López  2   9   10
Affiliations
Meta-Analysis

Blood pressure targets for hypertension in people with chronic renal disease

Juan Erviti et al. Cochrane Database Syst Rev. .

Abstract

Background: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease, development of end-stage renal disease, and all-cause mortality. It affects around 10% of the population worldwide. The prevalence of hypertension in people with CKD ranges from 22% in stage 1 to 80% in stage 4. Elevated arterial blood pressure is one of the major independent risk factors for adverse cardiovascular events. Thereby, reducing blood pressure to below standard targets may be beneficial but could also increase the risk of adverse events. The optimal blood pressure target in people with hypertension and CKD remains unknown.

Objectives: Primary: to compare the effects of standard and lower-than-standard blood pressure targets for hypertension in people with chronic kidney disease on mortality and morbidity outcomes. Secondary: to assess the magnitude of reductions in systolic and diastolic blood pressure, the proportion of participants reaching blood pressure targets, and the number of drugs necessary to achieve the assigned target.

Search methods: We used standard, extensive Cochrane search methods. We searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, one other database, and two trial registers up to 8 February 2023. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions.

Selection criteria: We included randomized controlled trials (RCTs) in people with hypertension and CKD that provided at least twelve months' follow-up. Eligible interventions compared lower targets for systolic/diastolic blood pressure (130/80 mmHg or lower) to standard targets for blood pressure (140 to 160/90 to 100 mmHg or lower). Participants were adults with CKD and elevated blood pressure documented in a standard way on at least two occasions, or already receiving treatment for elevated blood pressure.

Data collection and analysis: We used standard Cochrane methods. Our critical outcomes were: total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease. Important outcomes were: participant withdrawals due to adverse effects, and number of participants with a doubling of serum creatinine level or at least a 50% reduction in the glomerular filtration rate (GFR) at the end of the study. We used GRADE to assess the certainty of the evidence for the critical outcomes. This review received no funding.

Main results: We included six RCTs that contributed data for meta-analysis, involving 7348 participants overall (range 840 to 4733 people per study). The mean follow-up was 3.6 years (range 1.0 to 8.0 years). Three studies were publicly funded, two were privately funded, and one had both public and private funding. All RCTs provided individual participant data. None of the included studies blinded participants or clinicians because of the need to titrate antihypertensive drugs to reach a specific blood pressure target. However, an independent committee blinded to group allocation assessed clinical events in all studies. Critical outcomes. Compared with standard blood pressure targets, lower targets likely result in little to no difference in total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.76 to 1.06; 6 studies, 7348 participants), total serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 7348 participants), and total cardiovascular events (RR 1.00, 95% CI 0.87 to 1.15; 5 studies, 6508 participants), all with moderate-certainty evidence. Compared with standard blood pressure targets, lower targets may result in little to no difference in cardiovascular mortality (RR 0.90, 95% CI 0.70 to 1.16; 6 studies, 7348 participants) and progression to end-stage renal disease (RR 0.94, 95% CI 0.80 to 1.11; 4 studies, 4788 participants), both with low-certainty evidence. Important outcomes. We found little to no differences in: participant withdrawals due to adverse effects; and the number of participants with a doubling of serum creatinine level, or at least a 50% reduction in GFR at the end of the study. Exploratory outcomes. Compared to the standard blood pressure target groups, participants in the lower target groups achieved lower systolic and diastolic blood pressure values after one year, and required a higher number of antihypertensive drugs at the end of the studies. A higher proportion of participants in the standard blood pressure target groups achieved the targets they were assigned than did participants in the intensive target groups.

Authors' conclusions: Compared to a standard blood pressure target, lower blood pressure targets probably result in little to no difference in total mortality, total serious adverse events, and total cardiovascular events, and may result in little to no difference in total cardiovascular mortality or in the progression to end-stage renal disease in people with hypertension and CKD. However, the evidence underpinning these conclusions has several limitations. All studies were open design, blood pressure measurement was performed at a medical office, and there was scant information about adverse events. Future research should include high-quality adverse event data, report results for people with different levels of proteinuria, and consider out-of-office blood pressure monitoring. Several studies are ongoing, and may provide new evidence for this topic in the near future.

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Conflict of interest statement

Juan Erviti reports that he has no conflicts of interest.

Luis Carlos Saiz reports that he has no financial conflicts of interest. He is the Managing Editor of the Spanish satellite for the Cochrane Hypertension Group, and had no role in the editorial process for this review.

Leire Leache is a hospital pharmacist. She reports that she has no conflicts of interest.

José I Pijoan is an epidemiologist. He reports that he has no conflicts of interest.

Miguel Menéndez Orenga is a family doctor. He reports that he has no conflicts of interest.

Douglas Salzwedel: declares no financial conflicts of interest. He is the Cochrane Hypertension Information Specialist, and had no role in the editorial process for this review.

Iván Méndez‐López is an internist. He reports that he has no conflicts of interest.

Figures

1
1
PRISMA study flow diagram
1.1
1.1. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 1: Total mortality
1.2
1.2. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 2: Total serious adverse events
1.3
1.3. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 3: Total cardiovascular events
1.4
1.4. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 4: Cardiovascular mortality
1.5
1.5. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 5: Progression to end‐stage renal disease
1.6
1.6. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 6: Participant withdrawals due to adverse events
1.7
1.7. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 7: Doubling of serum creatinine level or 50% reduction in GFR at the end of study
1.8
1.8. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 8: Systolic blood pressure change from baseline at one year
1.9
1.9. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 9: Diastolic blood pressure change from baseline at one year
1.10
1.10. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 10: Proportion of participants reaching target blood pressure levels at end of study
1.11
1.11. Analysis
Comparison 1: Lower versus standard blood pressure targets, Outcome 11: Number of antihypertensive drugs that each participant needed at end of study
2.1
2.1. Analysis
Comparison 2: Lower versus standard targets: diabetic versus non‐diabetic subgroup, Outcome 1: Total mortality
2.2
2.2. Analysis
Comparison 2: Lower versus standard targets: diabetic versus non‐diabetic subgroup, Outcome 2: Total serious adverse events
2.3
2.3. Analysis
Comparison 2: Lower versus standard targets: diabetic versus non‐diabetic subgroup, Outcome 3: Total cardiovascular events
2.4
2.4. Analysis
Comparison 2: Lower versus standard targets: diabetic versus non‐diabetic subgroup, Outcome 4: Cardiovascular mortality
2.5
2.5. Analysis
Comparison 2: Lower versus standard targets: diabetic versus non‐diabetic subgroup, Outcome 5: Progression to end‐stage renal disease
3.1
3.1. Analysis
Comparison 3: Lower versus standard targets: male versus female subgroup, Outcome 1: Total mortality
3.2
3.2. Analysis
Comparison 3: Lower versus standard targets: male versus female subgroup, Outcome 2: Total serious adverse events
3.3
3.3. Analysis
Comparison 3: Lower versus standard targets: male versus female subgroup, Outcome 3: Total cardiovascular events
3.4
3.4. Analysis
Comparison 3: Lower versus standard targets: male versus female subgroup, Outcome 4: Cardiovascular mortality
3.5
3.5. Analysis
Comparison 3: Lower versus standard targets: male versus female subgroup, Outcome 5: Progression to end‐stage renal disease
4.1
4.1. Analysis
Comparison 4: Lower versus standard targets: younger than 75 versus 75 years and older subgroup, Outcome 1: Total mortality
4.2
4.2. Analysis
Comparison 4: Lower versus standard targets: younger than 75 versus 75 years and older subgroup, Outcome 2: Total serious adverse events
4.3
4.3. Analysis
Comparison 4: Lower versus standard targets: younger than 75 versus 75 years and older subgroup, Outcome 3: Total cardiovascular events
4.4
4.4. Analysis
Comparison 4: Lower versus standard targets: younger than 75 versus 75 years and older subgroup, Outcome 4: Cardiovascular mortality
4.5
4.5. Analysis
Comparison 4: Lower versus standard targets: younger than 75 versus 75 years and older subgroup, Outcome 5: Progression to end‐stage renal disease
5.1
5.1. Analysis
Comparison 5: Lower versus standard targets: primary versus secondary cardiovascular prevention subgroup, Outcome 1: Total mortality
5.2
5.2. Analysis
Comparison 5: Lower versus standard targets: primary versus secondary cardiovascular prevention subgroup, Outcome 2: Total serious adverse events
5.3
5.3. Analysis
Comparison 5: Lower versus standard targets: primary versus secondary cardiovascular prevention subgroup, Outcome 3: Total cardiovascular events
5.4
5.4. Analysis
Comparison 5: Lower versus standard targets: primary versus secondary cardiovascular prevention subgroup, Outcome 4: Cardiovascular mortality
5.5
5.5. Analysis
Comparison 5: Lower versus standard targets: primary versus secondary cardiovascular prevention subgroup, Outcome 5: Progression to end‐stage renal disease
6.1
6.1. Analysis
Comparison 6: Lower versus standard targets: GFR less than 30 mL/min versus 30 to 60 mL/min subgroup, Outcome 1: Total mortality
6.2
6.2. Analysis
Comparison 6: Lower versus standard targets: GFR less than 30 mL/min versus 30 to 60 mL/min subgroup, Outcome 2: Total serious adverse events
6.3
6.3. Analysis
Comparison 6: Lower versus standard targets: GFR less than 30 mL/min versus 30 to 60 mL/min subgroup, Outcome 3: Total cardiovascular events
6.4
6.4. Analysis
Comparison 6: Lower versus standard targets: GFR less than 30 mL/min versus 30 to 60 mL/min subgroup, Outcome 4: Cardiovascular mortality
6.5
6.5. Analysis
Comparison 6: Lower versus standard targets: GFR less than 30 mL/min versus 30 to 60 mL/min subgroup, Outcome 5: Progression to end‐stage renal disease
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References to other published versions of this review

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