News · Longevity & Aging
Tighter blood pressure control cut cardiovascular events with or without kidney disease in 27 trials
Pooling 88,830 participants, the analysis found 15% fewer cardiovascular events for each 10-point drop in systolic pressure. Kidney failure did not clearly differ, though falls of 30% or more in kidney filtration were more frequent.
- An analysis pooled 27 randomized trials with 88,830 participants, with and without chronic kidney disease.
- Each 10 mm Hg lower systolic pressure went with 15% fewer cardiovascular events, in both groups.
- That was 4.3 fewer events per 1,000 people a year with kidney disease and 2.7 without.
- Kidney failure did not clearly differ, but falls of 30% or more in kidney filtration were 42% more frequent.
- A 2024 Cochrane review of six trials in kidney disease had found little to no difference in events.
Chronic kidney disease raises the risk of heart attack and stroke as well as of kidney failure, and many of the people who have it also have high blood pressure. How hard to push that pressure down has been argued over for years. Lower pressure protects the heart. It can also make kidney test results look worse, and doctors have been wary of trading one organ for the other.
An analysis of 27 randomized trials, published this week in JAMA Cardiology with Fotini Iatridi as first author, concludes that the trade is worth making. Treating to lower targets prevented cardiovascular events just as well in people with kidney disease as in people without it, with no clear increase in kidney failure. It did produce more drops in a standard measure of kidney function, and what those drops mean is the part still open.
Why blood pressure targets in kidney disease were uncertain
Chronic kidney disease is common. It affects around 10% of the population worldwide, and high blood pressure travels with it. The prevalence of hypertension in people with CKD ranges from 22% in stage 1 to 80% in stage 4, the stages running from mildest to most severe.
The modern argument about targets began with a trial known as SPRINT. Its researchers randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). Systolic pressure is the top number in a reading. The trial was stopped early because the intensive group was doing better. Its main measure of heart attacks, strokes, heart failure and cardiovascular deaths occurred at 1.65% per year vs. 2.19% per year, the lower figure in the intensive group.
About 2,600 of those participants had kidney disease, and they were analyzed separately. The pattern was similar but the numbers were small. In that subgroup the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants, a difference that on its own could have been chance.
The kidneys gave a mixed signal. The main kidney outcome, a halving of function or kidney failure, occurred in 15 intensive group and 16 standard group participants. But after the initial 6 months, the intensive group had a slightly higher rate of change in eGFR, the blood-test estimate of kidney function. Their measured function, in other words, declined a little faster.
Reviews that pooled the available trials did not agree. In 2024 a Cochrane review restricted itself to trials in people with both high blood pressure and kidney disease. It found six that contributed data for meta-analysis, involving 7348 participants overall. Its conclusion was that lower blood pressure targets probably result in little to no difference in total mortality, total serious adverse events, and total cardiovascular events.
What the analysis of 27 trials did
The new paper cast a wider net. It starts from the same doubt. There is uncertainty about the effects of intensive blood pressure (BP) lowering on risks of cardiovascular disease and kidney failure in patients with chronic kidney disease (CKD), the authors write.
They searched for every trial of the right kind. Randomized clinical trials comparing intensive vs standard BP lowering in adults with and without CKD, with at least 1 year of follow-up, were eligible for inclusion. That produced 27 studies with 88,830 participants.
Two choices set the analysis apart. First, it included people without kidney disease, so that the two groups could be compared directly inside the same trials.
Second, it put the trials on a common scale. Trials differ in how far apart their two groups end up: in one the intensive group may finish 15 points lower, in another only 5. The results were combined after standardizing trial results according to the between-group difference in achieved systolic pressure. Every result is therefore expressed per 10 mm Hg of extra lowering.
Fewer cardiovascular events, with or without kidney disease
The main result is a single number. Intensive treatment reduced the risk of cardiovascular events by 15% per 10-mm Hg lower systolic pressure, with a plausible range of 11% to 19%. The reduction was the same size, proportionally, in people with kidney disease and in people without.
Proportional reductions hide a difference that matters. People with kidney disease have more heart attacks and strokes to begin with, so the same percentage removes more of them.
| Fewer cardiovascular events per 1,000 people treated for a year | |
|---|---|
| With chronic kidney disease | 4.3 |
| Without chronic kidney disease | 2.7 |
The paper counts events per 1000 person-years in individuals with CKD and in those without, a person-year being one person followed for one year. Carried over five years, those rates would come to roughly 22 and 14 events avoided for every 1,000 people. The authors make the comparison explicit: since baseline cardiovascular risk is higher in CKD, the absolute reduction in cardiovascular events was at least as large in this population.
What tighter blood pressure control did to the kidneys
The kidney results depend on which measure is used.
On kidney failure itself, the analysis found no clear harm. Intensive BP lowering did not affect risk of kidney failure. The estimate was 3% lower, with a range from 16% lower to 11% higher.
The picture changes with a blood test. Kidney function is tracked by the estimated glomerular filtration rate (eGFR), a calculation of how much blood the kidneys filter each minute. Trials count how many people’s eGFR falls by a set fraction and stays down.
| Kidney measure | Effect of intensive treatment per 10 mm Hg |
|---|---|
| Kidney failure | No clear difference |
| eGFR down by 57% | No clear difference |
| eGFR down by 50% | No clear difference, estimate 29% higher |
| eGFR down by 40% or more | 47% more frequent |
| eGFR down by 30% or more | 42% more frequent |
The excess appeared with declines of 30% or 40%, which are the more moderate and more common ones. For the largest declines the analysis found no clear difference. The authors’ summary is that it increased the risk of sustained declines in eGFR, without an increase in risk of kidney failure.
Whether those declines are a harmless shift in how hard the kidneys are filtering, or early damage that would take longer than a trial to become kidney failure, is not something the pooled results can settle. Most blood pressure trials last a few years. Kidney failure can take much longer to develop.
The authors come down on one side. Their conclusion is that intensive BP lowering should be recommended in people with and without CKD.
How the result fits with earlier trials and reviews
It agrees with the largest body of evidence on a related question. In April this year a collaboration of trial groups published an analysis in The Lancet of 285,124 participants from 46 trials, about a fifth of whom had kidney disease. Those trials tested blood pressure drugs against a comparator, a broader category than intensive against standard targets. A 5 mm Hg reduction in systolic blood pressure reduced the risk of major cardiovascular disease in individuals with CKD by 9%, and by 10% in those without. The reductions were consistent across all CKD stages, including severe stages 4 and 5.
That analysis carried a warning the new one does not repeat. In people with kidney disease the benefit was attenuated among those with coexisting diabetes.
It also fits an older pooled analysis of deaths. In 2017 a review of 18 trials found that in people with moderate to severe kidney disease, more intensive vs less intensive BP control resulted in 14.0% lower risk of death from any cause.
It disagrees with the Cochrane review, and size is the plainest reason. Six trials and 7,348 people is a twelfth of the participants in the new analysis. The Cochrane reviewers also compared targets as assigned, whatever pressure difference resulted, and they were candid about the trials themselves. All studies were open design, blood pressure measurement was performed at a medical office, and there was scant information about adverse events.
What the pooled trials cannot say
Whether the kidney signal is benign. This is the main open question. The analysis shows more falls of 30% and 40% in eGFR, and no clear difference in kidney failure, within the length of the trials.
What it costs to get there. Lower targets take more medicine. In the Cochrane review, people assigned to lower targets required a higher number of antihypertensive drugs at the end of the studies. In SPRINT, the intensive group had more episodes of low blood pressure, fainting and acute kidney injury. Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group. Hypotension means blood pressure that is too low, and syncope means fainting.
Who was in the trials. Trial participants are selected and closely monitored. People with advanced kidney disease have often been left out of blood pressure trials, and the results apply to them with less confidence.
Diabetes. The Lancet analysis found a weaker benefit in people who had both kidney disease and diabetes. The headline figures in the new analysis are averages over all participants, and an average can hide a group that gains less.
A pooled average. Expressing everything per 10 mm Hg assumes that each further point of lowering buys the same benefit, whatever the starting pressure. That is a modeling choice, and an individual trial might not follow it.
Method. This is a meta-analysis of published trial results. It is only as good as the trials and the way they reported their outcomes.
The target that suits a particular person depends on their age, their other conditions and how they tolerate treatment, which is assessed by their doctor. Do not stop or change a prescribed medicine without talking to your doctor.
Lowering systolic blood pressure by a further 10 mm Hg went with 15% fewer cardiovascular events in people with and without chronic kidney disease and no increase in kidney failure across 27 randomized trials with 88,830 participants, alongside more frequent falls of 30% or more in a blood measure of kidney function whose long-term meaning the trials were too short to show.
People also ask
What counts as intensive blood pressure lowering?
It means treating to a lower target than usual. In the best-known trial, the intensive group aimed for a systolic pressure, the top number, below 120 mm Hg, and the standard group for below 140 mm Hg.
What did the analysis find?
Across 27 trials, each 10 mm Hg lower systolic pressure went with a 15% lower risk of cardiovascular events, and the benefit was the same in people with and without chronic kidney disease. In absolute terms it was larger with kidney disease: 4.3 fewer events per 1,000 people a year, against 2.7.
Did tighter control harm the kidneys?
Kidney failure did not clearly differ: the estimate was 3% lower, with a range from 16% lower to 11% higher. Readings of kidney filtration did fall more often: declines of 30% or more were 42% more frequent with intensive treatment. Whether such falls matter over a longer period than the trials covered is not settled.
Why did an earlier review find no benefit?
A 2024 Cochrane review pooled six trials with 7,348 participants, all with kidney disease, and found little to no difference in cardiovascular events. The new analysis is twelve times larger and scales each trial's result to the difference in blood pressure it actually achieved.
What are the limits of the analysis?
It combines trials that used different targets, drugs and definitions, most of them for only a few years. The outcomes it pooled were cardiovascular events and kidney measures; harms such as dizziness and fainting are known from individual trials. The right target for a particular person is assessed by their doctor. This is general information rather than medical advice.
References
- Iatridi, F., Roddick, A. J., Staplin, N., et al. Intensive vs Standard Blood Pressure Lowering in People With and Without Chronic Kidney Disease. JAMA Cardiology, 2026.
- SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. New England Journal of Medicine, 2015.
- Cheung, A. K., Rahman, M., Reboussin, D. M., et al. Effects of Intensive BP Control in CKD. Journal of the American Society of Nephrology, 2017.
- Erviti, J., Saiz, L. C., Leache, L., et al. Blood pressure targets for hypertension in people with chronic renal disease. Cochrane Database of Systematic Reviews, 2024.
- Zeng, G., Bidel, Z., Yang, Q., et al. Pharmacological blood-pressure lowering for the prevention of cardiovascular disease and death across the full spectrum of chronic kidney disease severity: an individual-participant data meta-analysis. The Lancet, 2026.
- Malhotra, R., Nguyen, H. A., Benavente, O., et al. Association Between More Intensive vs Less Intensive Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease Stages 3 to 5. JAMA Internal Medicine, 2017.