Blood Pressure Lowering Across CKD Stages: Meta-Analysis Findings

Key Takeaways

• Each 5 mm Hg reduction in systolic blood pressure was associated with a ~9–10% relative reduction in major cardiovascular events, with similar effects in participants with and without CKD.
• Across subgroups, major antihypertensive classes showed similar relative effects versus placebo, supporting a class-agnostic benefit driven by blood pressure reduction itself.

A Lancet individual-participant data meta-analysis associated 5 mm Hg reductions in systolic blood pressure with lower risk of major cardiovascular events, with a similar relative effect in participants with chronic kidney disease and those without it.

The analysis pooled a large set of randomized comparisons of blood-pressure-lowering therapy versus comparator for subgroup testing. It focused on major cardiovascular events rather than kidney-specific outcomes, using a common trial endpoint across the included populations. Across CKD and non-CKD groups, the relative treatment effect was closely similar.

The investigators performed a one-stage individual-participant data meta-analysis of randomized trials from the Blood Pressure Lowering Treatment Trialists’ Collaboration, without age-based entry criteria. Eligible trials required at least 1000 person-years of follow-up in each arm, baseline blood-pressure and creatinine measurements, and time-to-event outcomes. Trials with unclear randomisation, those restricted to heart failure or acute care settings, and participants with documented heart failure or extreme creatinine values were excluded.

Of 52 randomized trials, 285,124 participants from 46 eligible trials were included, with 20.7% having CKD and 30.2% having type 2 diabetes at baseline. Median follow-up was 4.4 years, and the primary endpoint was major cardiovascular events, comprising fatal or non-fatal stroke, ischemic heart disease, or hospitalisation for, or death from, heart failure.

Each 5 mm Hg reduction in systolic blood pressure was associated with lower major cardiovascular event risk in participants with CKD, with an HR of 0.91 (95% CI 0.87–0.94). Among those without CKD, the corresponding estimate was 0.90 (95% CI 0.88–0.93), with no evidence of heterogeneity by CKD status. Researchers also reported no heterogeneity across CKD stages, including stages 4–5. Relative effects were also similar by proteinuria status and across baseline blood-pressure categories down to less than 120/70 mm Hg.

Within the CKD subgroup, the relative treatment effect was attenuated in participants with diabetes, with an HR of 0.96 (95% CI 0.90–1.02). Among participants with CKD but without diabetes, the corresponding estimate was 0.88 (95% CI 0.84–0.93), and the interaction p value was 0.044. This differed from the broader consistency seen across the analyzed CKD subgroups. A stratified network meta-analysis also indicated that class-specific effects of principal antihypertensive agents versus placebo were similar across the investigated subgroups. Overall, the findings combined broadly similar relative effects across CKD strata with an attenuation signal among participants with both CKD and diabetes.