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Blood-pressure targets

TL;DR — Seven large randomised trials now bear directly on how low to go, and the weight of evidence has shifted decisively toward a systolic target below 120–130 mm Hg for people at elevated cardiovascular risk. SPRINT's final report gave 1.77% vs 2.40% per year for the primary composite (HR 0.73, 95% CI 0.63–0.86) and all-cause mortality 1.06% vs 1.41% per year (HR 0.75, 0.61–0.92) (SPRINT 2021, PMID 34010531). The long-standing exception — ACCORD-BP's null result in type 2 diabetes (HR 0.88, 95% CI 0.73–1.06) (ACCORD 2010, PMID 20228401) — has been overturned twice: ESPRIT in 11,255 high-risk Chinese adults including 4,359 with diabetes (HR 0.88, 0.78–0.99, no heterogeneity by diabetes status) (Liu 2024, PMID 38945140) and BPROAD in 12,821 people with type 2 diabetes (HR 0.79, 0.69–0.90) (Bi 2025, PMID 39555827). A participant-level pooling of six trials and 80,220 participants gives the trade-off in usable form: 1.73% absolute risk reduction in cardiovascular disease (NNT 58) against 1.82% absolute increase in adverse events of interest (NNH 55), with net benefit still positive (Guo 2025, PMID 40902616). The residual disagreement is not really about the trials — it is about whether a target attained by unattended automated office measurement can be transcribed into routine clinic practice, and about frail and very old people, in whom the evidence thins fast.

The trials, side by side

Trial n Population Targets Achieved SBP Primary result Key harms
SPRINT (PMID 26551272; final PMID 34010531) 9,361 ≥50y, SBP ≥130, high CV risk, no diabetes or prior stroke <120 vs <140 121.4 vs 136.2 at 1y Composite 1.77 vs 2.40%/yr, HR 0.73 (0.63–0.86); all-cause death HR 0.75 (0.61–0.92) More hypotension, syncope, electrolyte abnormality, AKI; not more injurious falls
ACCORD-BP (PMID 20228401) 4,733 Type 2 diabetes, high CV risk <120 vs <140 119.3 vs 133.5 at 1y Composite 1.87 vs 2.09%/yr, HR 0.88 (0.73–1.06), p=0.20; stroke HR 0.59 (0.39–0.89) Serious treatment-attributed AEs 3.3% vs 1.3%
STEP (PMID 34491661) 8,511 Chinese, 60–80y 110–<130 vs 130–<150 127.5 vs 135.3 at 1y Composite 3.5% vs 4.6%, HR 0.74 (0.60–0.92) More hypotension only
STEP 6-year extension (PMID 41105077) 8,511 Same, all intensive after trial Sustained vs delayed intensive 127.9 vs 129.5 1.12 vs 1.33%/yr, HR 0.82 (0.71–0.96); earlier initiation better More hypotension
ESPRIT (PMID 38945140) 11,255 High CV risk; 4,359 diabetes, 3,022 prior stroke <120 vs <140 119.1 vs 134.8 Composite 9.7% vs 11.1%, HR 0.88 (0.78–0.99) Syncope HR 3.00 (1.35–6.68); no excess hypotension, electrolyte abnormality, injurious fall or AKI
BPROAD (PMID 39555827) 12,821 Type 2 diabetes ≥50y, China <120 vs <140 121.6 vs 133.2 at 1y 1.65 vs 2.09 events/100 py, HR 0.79 (0.69–0.90) More symptomatic hypotension and hyperkalaemia; serious AEs similar
SPS3 (PMID 23726159) 3,020 Recent MRI-defined lacunar stroke <130 vs 130–149 127 vs 138 at 1y All stroke HR 0.81 (0.64–1.03), p=0.08; intracerebral haemorrhage HR 0.37 (0.15–0.95) Treatment-related serious AEs infrequent
HYVET (PMID 18378519) 3,845 Age ≥80, SBP ≥160 Treat to 150/80 vs placebo 15.0/6.1 mm Hg lower on treatment at 2y Stroke −30% (95% CI −1 to 51, p=0.06); all-cause death −21% (4–35); heart failure −64% (42–78) Fewer serious AEs than placebo

Why ACCORD-BP was the outlier, and what replaced it

ACCORD-BP was underpowered for its observed event rate, had a factorial glycaemia arm, and produced a stroke result (HR 0.59, 95% CI 0.39–0.89) discordant with its null composite (ACCORD 2010, PMID 20228401). For a decade it was the reason guidelines held a separate, more permissive target for diabetes. Two subsequent trials removed that reason. ESPRIT prespecified diabetes and prior-stroke subgroups and found no heterogeneity (Liu 2024, PMID 38945140). BPROAD randomised 12,821 people with type 2 diabetes to the same targets and found a 21% relative reduction (Bi 2025, PMID 39555827). Meta-analyses of the diabetes question, done before and after these trials, have moved accordingly (Ioannidou 2023, PMID 37257222; Saad 2025, PMID 40769802; Akhtar 2026, PMID 41266861). Post-hoc work in ACCORD continues to identify subgroups that may have benefited (Jiao 2024, PMID 38297986; Wang 2025, PMID 40685691).

Age

  • Relative benefit persists into old age. BPLTTC age-stratified individual-participant analysis of 358,707 people from 51 trials: HR per 5 mm Hg systolic reduction 0.82 (95% CI 0.76–0.88) under 55, 0.91 (0.88–0.95) at 55–64, 0.91 (0.88–0.95) at 65–74, 0.91 (0.87–0.96) at 75–84, and 0.99 (0.87–1.12) at ≥85 (adjusted p for interaction 0.050); absolute risk reductions were larger in older groups. The authors' explicit recommendation is removal of age-related blood-pressure thresholds from guidelines (BPLTTC 2021, PMID 34461040).
  • Trial-level evidence for lower over higher targets in older adults. Cochrane's 2024 update (4 trials, 16,732 participants, mean age 70.3) found that a target of ≤140/90 versus 150–160/95–105 mm Hg reduces stroke (RR 1.33 favouring the lower target, 95% CI 1.06–1.67, high certainty) and likely reduces total serious cardiovascular events (RR 1.25, 1.09–1.45, moderate certainty), with unclear effect on all-cause mortality (RR 1.14, 0.95–1.37, low certainty) and no increase in withdrawal for adverse effects (Falk 2024, PMID 39688187).
  • The frailty caveat is real and under-evidenced. The Cochrane authors explicitly flag people ≥80 and those who are frail as needing further research (Falk 2024, PMID 39688187), and observational and secondary-analysis work suggests treatment-related harm rises with frailty (Sheppard 2023, PMID 37075078; Nguyen 2021, PMID 34035077; Wenjie 2025, PMID 39915072). Earlier syntheses concluded lower targets did not increase falls or cognitive impairment but did increase hypotension, syncope and pill burden (Weiss 2017, PMID 28114673). Managing octogenarians with polypharmacy is a distinct problem (Benetos 2015, PMID 26172896). See special populations.

The benefit–harm ledger

The pooled participant-level analysis of ACCORD-BP, SPRINT, ESPRIT, BPROAD, STEP and CRHCP (80,220 participants, median follow-up 3.2 years, 82.6% Asian) quantifies the trade explicitly: composite cardiovascular events 5.3% vs 7.1% (HR 0.76, 95% CrI 0.72–0.81), absolute risk reduction 1.73% (95% CrI 1.65–1.81), NNT 58 (55–61); adverse events of interest absolute risk increase 1.82% (1.63–2.01), NNH 55 (49–61); net benefit 1.14 (1.03–1.25) using adjudicated weighting, and 1.13 (1.01–1.24) when kidney-related events are included (Guo 2025, PMID 40902616). The near-equality of NNT and NNH is the honest headline: intensive treatment trades roughly one adverse event for one prevented cardiovascular event, and it is favourable only because the events differ in severity. Independent syntheses reach similar conclusions (Rizwanullah 2025, PMID 40772210).

Kidney outcomes deserve separate attention: an eGFR decline on intensification may be haemodynamic rather than structural, and post-hoc analyses of SPRINT and ACCORD have examined this (Xu 2025, PMID 41117098; Cheung 2017, PMID 28642330; Aggarwal 2019, PMID 31067189).

Why guidelines set different numbers from the same trials

Body Target
2025 AHA/ACC (PMID 40811516) <130/80 mm Hg for most adults on treatment
2024 ESC (PMID 39210715) 120–129 systolic where tolerated, with an explicit tolerability caveat
2023 ESH (PMID 37345492) <140/90 first, then toward 130/80 if tolerated
2021 WHO (PMID 34775787) <140/90; <130/80 in established CVD or high risk
2025 Hypertension Canada (PMID 40419299) <130 systolic
2021 KDIGO, CKD (PMID 33637192) <120 systolic, standardised office measurement

Three sources of divergence account for nearly all of it. Measurement: SPRINT used unattended automated office readings, which run lower than conventional office readings by an amount too heterogeneous to convert reliably (Andreadis 2019, PMID 31290085; Salvetti 2019, PMID 30686088) — so "<120" in SPRINT is not "<120" in a clinic. Population: SPRINT excluded diabetes and prior stroke, so its estimate needed external validation, which ESPRIT and BPROAD supplied years later (Liu 2024, PMID 38945140; Bi 2025, PMID 39555827). Framing: a body that treats a target as a population-level policy weighs the NNH differently from one treating it as an individual clinical goal (Guo 2025, PMID 40902616; Touyz 2019, PMID 31030859). KDIGO's <120 recommendation in chronic kidney disease is the most aggressive and has been criticised precisely on the measurement point (Carriazo 2022, PMID 35498896; Tomson 2021, PMID 34152826; Cheung 2021, PMID 33637203).

What is being achieved, versus targeted

SPRINT's intensive arm required a mean of about one additional drug and intensive visit schedules to reach 121.4 mm Hg (Cushman 2022, PMID 35766041). Real-world US control to the older <140/90 standard was 43.7% in 2017–2018 (Muntner 2020, PMID 32902588). A target is only a policy instrument if the delivery system can reach it — see adherence and implementation. STEP's extension adds a timing dimension: the earlier intensive treatment starts after diagnosis, the larger the benefit (relative risk 0.83 for immediate vs 0.88 for 12-month-delayed initiation), which reframes the target debate as partly a question about delay rather than about the number (Song 2025, PMID 41105077).

Open questions

  • What systolic value measured by routine attended office readings corresponds to SPRINT's <120 mm Hg? No conversion with acceptable precision exists (Andreadis 2019, PMID 31290085).
  • Is there any population in which intensive targets are net-harmful? Frailty is the leading candidate and the least well studied (Falk 2024, PMID 39688187; Sheppard 2023, PMID 37075078).
  • Should there be a diastolic floor? SPS3, SPRINT and BPROAD did not use one; observational data suggest harm below 60–70 mm Hg at high pulse pressure (McEvoy 2016, PMID 27590090).
  • Given that NNT (58) and NNH (55) are nearly equal, what patient-preference weighting justifies a universal target rather than an individualised one? (Guo 2025, PMID 40902616)
  • SPS3 showed a significant reduction only in intracerebral haemorrhage (HR 0.37, 95% CI 0.15–0.95) with a non-significant all-stroke result — is target-setting after lacunar stroke a haemorrhage-prevention decision rather than an ischaemia-prevention one? (SPS3 2013, PMID 23726159)
  • Does earlier initiation matter more than the achieved number, as the STEP extension implies? (Song 2025, PMID 41105077)

References

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