Long-term follow-up of ASCOT-BPLA showed systolic blood pressure (SBP) variability was a strong predictor of CV outcomes independent of mean SBP, even in patients with well-controlled SBP. Additionally, amlodipine-based treatment reduced the risk of CV events compared with atenolol-based treatment.

This summary is based on the publication of Gupta A, Whiteley WN, Godec T, et al. - Legacy benefits of blood pressure treatment on cardiovascular events are primarily mediated by improved blood pressure variability: the ASCOT trial. Eur Heart J. 2024 Jan 31:ehad814 [Online ahead of print]. doi: 10.1093/eurheartj/ehad814

Introduction and methods

Background

Observational studies have demonstrated blood pressure variability (BPV) is an important predictor of morbidity and mortality [1,2]. However, it is unclear what the long-term effect of a period of pharmacological BP control but with possible BPV is, as indicated by the results of the ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure-Lowering Arm) trial [3-7].

Aim of the study

In the ASCOT Legacy study, a long-term follow-up study of the ASCOT-BPLA trial, the authors investigated the impact of in-trial visit-to-visit systolic BPV and mean systolic BP (SBP) on long-term fatal and nonfatal CV outcomes. They also compared the time to first occurrence of prespecified CV events between 2 antihypertensive treatment strategies.

Methods

In the original ASCOT-BPLA trial, 19,257 patients with hypertension aged 40–79 years at randomization who had ≥3 additional CVD risk factors but no history of prior coronary heart disease (CHD) events, currently treated angina, stroke, or TIA within 3 months were randomized to a amlodipine-based (amlodipine plus perindopril if necessary) or atenolol-based (atenolol plus bendroflumethiazide if necessary) treatment strategy. The trial was stopped prematurely in December 2004 (after a median follow-up duration of 5.5 years) at the recommendation of the Data Safety and Monitoring Board because of a significantly higher mortality rate in patients allocated to the atenolol-based treatment compared with those receiving amlodipine-based treatment.

In the ASCOT Legacy study, 8580 participants from the UK (4305 assigned to amlodipine-based treatment strategy and 4275 to atenolol-based treatment strategy) were followed up for a median duration of 17 years (IQR: 9–19; maximum: 21), using linked hospital and mortality records. Data of 7092 participants with completed records were available for the post-trial analysis.

Outcomes

Prespecified CV events were: fatal and nonfatal stroke, nonfatal MI and fatal CHD, total coronary events, fatal and nonfatal HF, total CV events and procedures, AF, CV death, and all-cause mortality.

Main results

Impact of in-trial systolic BPV and mean SBP on later CV events

• In an analysis adjusted for baseline confounders and occurrence of stroke or MI historically or during the trial up to the post-trial period, the mean in-trial SBP was a predictor of post-trial long-term CV outcomes, including total CV events (adjusted HR: 1.14; 95%CI: 1.10–1.17; P<0.001), total stroke (adjusted HR: 1.19; 95%CI: 1.11–1.26; P<0.001), nonfatal MI and fatal CHD (adjusted HR: 1.19; 95%CI: 1.12–1.27; P<0.001), and CV death (adjusted HR: 1.22; 95%CI: 1.16–1.29; P<0.001), for each 10.0 mmHg of SD increase in mean SBP.
• Further adjustment for mean in-trial SBP indicated visit-to-visit systolic BPV was a stronger predictor of CV outcomes (per 5.0 mmHg of SD rise in systolic BPV), such as total CV events (adjusted HR: 1.22; 95%CI: 1.18–1.26; P<0.001), total stroke (adjusted HR: 1.20; 95%CI: 1.11–1.29; P<0.001), nonfatal MI and fatal CHD (adjusted HR: 1.25; 95%CI: 1.16–1.35; P<0.001), and CV death (adjusted HR: 1.28; 95%CI: 1.20–1.37; P<0.001).
• In the group with mean in-trial SBP <140 mmHg, patients in the highest third of systolic BPV (13.00–50.06 mmHg) showed an absolute increase in CV events of 16% (17 events per 1000 patient-years) compared with the lowest third (1.15–9.30 mmHg) over the 15-year post-trial follow-up period. Moreover, 53% of all CV events occurred in patients with well-controlled SBP (i.e., <140 mmHg; this comprised 44% of trial population).
• Patients with mean SBP <133 mmHg over a 5-year period had a 31% increased risk of total CV events if their systolic BPV ranged from 9.31 to 12.99 mmHg and a 65% excess risk if systolic BPV was 13.00–50.06 mmHg.

Effect of antihypertensive treatments on first CV events

• Analysis of the maximum 21-year follow-up data showed that in-trial amlodipine-based treatment was associated with a reduced risk of stroke (adjusted HR: 0.82; 95%CI: 0.72–0.93; P=0.003), total CV events (adjusted HR: 0.93; 95%CI: 0.88–0.98; P=0.008), total coronary events (adjusted HR: 0.92; 95%CI: 0.86–0.99; P=0.024), and AF (adjusted HR: 0.91; 95%CI: 0.83–0.99; P=0.030) compared with the atenolol-based treatment strategy.
• There was weaker evidence for a decreased risk of CV death (adjusted HR: 0.91; 95%CI: 0.82–1.01; P=0.073), and no significant differences in the incidence of nonfatal MI and fatal CHD, total HF, and all-cause mortality were found between treatments (all P>0.05).

Conclusion

In this long-term (up to 21 years) follow-up study of the ASCOT-BPLA trial, in-trial systolic BPV was a strong predictor of CV outcomes independent of mean SBP, even in patients with well-controlled SBP but high systolic BPV. In addition, an amlodipine-based treatment strategy during the trial was associated with reduced risks of total CV events, stroke, coronary events, and AF compared with atenolol-based treatment.

The authors point out that “[t]he original results of ASCOT-BPLA influenced national and international guidelines for hypertension. The current observations extend the benefits reported in the trial for the amlodipine-based treatment regimen and highlight the increasing importance of visit-to-visit systolic BPV in the prediction of long-term CV outcomes.”

Find this article online at Eur Heart J.

References

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