Is SBP <120 mmHg better than <140 mmHg in patients with diabetes or previous stroke?

In Chinese hypertensive patients at high CVD risk, intensive treatment targeting SBP <120 mmHg reduced major vascular events and mortality but increased kidney outcomes, compared with standard treatment targeting <140 mmHg, regardless of diabetes status or history of stroke.

This summary is based on the publication of Liu J, Li Y, Ge J, et al. - Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial. Lancet. 2024 Jul 20;404(10449):245-255. doi: 10.1016/S0140-6736(24)01028-6

Introduction and methods

Background

Lowering blood pressure (BP) is one of the most effective treatments to prevent CV events [1]. However, due conflicting evidence from RCTs, it is not clear whether targeting a systolic BP (SBP) <120 mmHg is better than <140 mmHg. The few trials conducted did have a different study design and study population (patients with or with no diabetes or previous stroke) [2-4].

Aim of the study

The authors investigated the efficacy and safety of intensive BP-lowering treatment targeting a SBP <120 mmHg compared with standard treatment targeting <140 mmHg in patients with high CVD risk and increased SBP, stratified by diabetes status and history of stroke.

Methods

The ESPRIT (Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing RIsk of Vascular evenTs) trial was a multicenter, open-label, blinded-outcome RCT conducted at 116 hospitals or community medical centers in China. Using minimized randomization with site stratification, 11,255 patients aged ≥50 years with SBP 130–180 mmHg and high CVD risk (i.e., established CVD or ≥2 major CVD risk factors) were assigned to intensive treatment targeting office SBP <120 mmHg or standard treatment targeting <140 mmHg. Major exclusion criteria included known secondary cause of hypertension, LVEF <35%, and eGFR <45 mL/min/1.73 m².

At each office visit, a trained investigator measured BP using an electronic BP monitor according to the standard procedure (i.e., following quiet rest for ≥5 minutes, 3 BP measurements were conducted in the seated participant with 1-minute intervals). The mean value of the 3 measurements was used as the BP level. To optimize medication adherence, the researchers provided free drugs covering the 5 classes of evidence-based antihypertensive medications (i.e., ACEi, ARB, calcium channel blockers, thiazide-type diuretic, and beta-blocker).

Other antihypertensive drugs were also allowed. Of the 11,255 participants, 4359 (38.7%) had diabetes and 3022 (26.9%) had previously experienced a stroke. Median follow-up duration was 3.4 years (IQR: 3.0–3.4).

Outcomes

The primary endpoint was a composite outcome of MI, revascularization (coronary or noncoronary), hospitalization or emergency room visit for HF, stroke, or CV death. Prespecified secondary endpoints included the individual components of the primary composite endpoint; all-cause mortality; a composite outcome of the primary endpoint or all-cause mortality; and a composite kidney outcome (i.e., end-stage renal disease, sustained eGFR decline to <10 mL/min/1.73 m², renal death, or sustained eGFR decline ≥40% from baseline).

Safety analysis included the assessment of serious adverse events and adverse events of special interest.

Main results

Efficacy

• At baseline, the mean SBP was 146.8 mmHg (SD: 10.5) in the intensive-treatment group (n=5624) and 147.0 mmHg (SD: 10.7) in the standard-treatment group (n=5631). This decreased to 119.1 mmHg (SD: 11.1) and 134.8 mmHg (SD: 10.5), respectively, during the follow-up period (excluding first 3 months of titration).
• During the follow-up, the primary endpoint event occurred in 547 patients (9.7%) in the intensive-treatment group and 623 (11.1%) in the standard-treatment group (HR: 0.88; 95%CI: 0.78–0.99; P=0.028).
• Subgroup analysis showed no heterogeneity in the effect of intensive treatment versus standard treatment on the primary endpoint by diabetes status, diabetes duration, or history of stroke.
• Of the secondary endpoints, the rates of CV death (1.1% vs. 1.7%; HR: 0.61; 95%CI: 0.44–0.84; P=0.0027), all-cause mortality (2.8% vs. 3.6%; HR: 0.79; 95%CI: 0.64–0.97; P=0.025), the composite outcome of the primary endpoint or all-cause mortality (11.3% vs. 12.7%; HR: 0.89; 95%CI: 0.80–0.99; P=0.039), and the composite kidney outcome (3.0% vs. 1.8%; HR: 1.70; 95%CI: 1.33–2.17) showed significant differences between the intensive-treatment and standard-treatment groups.

Safety

• Serious adverse events occurred in 42.1% of the patients receiving intensive treatment and 42.2% of those randomized to standard treatment (HR: 1.01; 95%CI: 0.95–1.07; P=0.78).
• The frequency of serious adverse events of syncope was higher in the intensive-treatment group than the standard-treatment group (0.4% vs. 0.1%; HR: 3.00; 95%CI: 1.35–6.68; P=0.0071).
• However, there were no significant differences in the rate of serious adverse events of hypotension (0.1% vs. 0.1%), electrolyte abnormalities (0.2% vs. 0.2%), injurious falls (0.5% vs. 0.4%), or acute kidney injury events (0.1% vs. <0.1%) between the intensive-treatment and standard-treatment groups (all P>0.05).

Conclusion

In the large, Chinese ESPRIT trial among patients with hypertension and high CVD risk, intensive treatment targeting SBP <120 mmHg reduced the risk of major vascular events and mortality compared with standard treatment targeting <140 mmHg, regardless of diabetes status or history of stroke. However, the intensive strategy was associated with an increased risk of the composite kidney outcome, which the authors will continue to monitor in long-term post-trial follow-up. The treatment strategies had a similar safety profile, although the frequency of serious adverse events of syncope was higher with intensive treatment.

The authors caution that the strategy of targeting SBP <120 mmHg should not be extended to all patients. In this study, patients could maintain their lowest SBP level if SBP <120 mmHg was not tolerated. Still, “[t]he strategy of targeting systolic blood pressure of less than 120 mmHg with common, accessible, and affordable drugs is feasible [and will] benefit hypertensive patients with high risk of cardiovascular disease and prevent excess acute injury.”

Find this article online at Lancet.

References

1. Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016; 387: 957–67.
2. Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015; 373: 2103–16.
3. Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010; 362: 1575–85.
4. Kitagawa K, Yamamoto Y, Arima H, et al. Effect of standard vs intensive blood pressure control on the risk of recurrent stroke: a randomized clinical trial and meta-analysis. JAMA Neurol 2019; 76: 1309–18.