THE RELATIONSHIP BETWEEN BP-CONTROL, BP -VARIABILITY AND ANTIHYPERTENSIVE TREATMENT WITH THE LONG-TERM RISK OF CARDIOVASCULAR EVENT: LESSONS FROM THE ASCOT-LEGACY 20 YEAR FOLLOW-UP

Abstract

Objective: The long-term cardiovascular (CV) impact of a period of blood pressure (BP)-control and -variability (BPV) achieved on different BP-lowering treatments is unclear. The findings will inform the debate on BP-control targets, and explore the reason of legacy effects. Design and method: In the ASCOT-Legacy Study, 7092 hypertensive patients (assigned to either amlodipine- or atenolol-based treatment [3588 and 3504, respectively] and survived for the first 5.5 years [landmark period]), were evaluated using > 100,000 BP records to estimate 5-year mean SBP and standard deviation [SD] of all reported SBPs (denoting 5-year BPV). Patients were subsequently followed using electronic health records for up to16-years [IQR: 9.1–19.3 years] for the first occurrence of fatal/non-fatal heart failure, non-fatal myocardial infarction/fatal-coronary heart disease, total coronary events (TCE) and total CV events. Cox proportional hazards from the end of the landmark period were used to estimate the hazard ratio [HR] associated with mean BP-control, BPV, and assigned treatment after adjustments (see Table) Results: During the landmark period, those on amlodipine-based (vs. atenolol-based) treatment had lower mean SBP (-1.71 mm Hg, p < 0.001) and BPV (SD, -1.99, p < 0.001). Table 1 shows that increase in mean SBP and BPV was associated with a significantly increased risk of all 4 outcomes, with the magnitude of risk higher for each SD rise in the BPV vs. SD rise of mean SBP. Adjustment of mean BP for BPV and vice versa attenuated the magnitude of mean SBP but not that associated with BPV. Those on amlodipine-based (vs atenolol-based) treatment showed long-term beneficial legacy effect with a 7% significant reduction of CV events. However, this long-term treatment benefit (legacy effect) becomes insignificant after adjusting for BPV. Those who have mean SBP > = 140 (vs SBP < 130) and BPV > = 15 mm Hg (vs < 10) continue to have a significant excess risk of TCE (45% [95%CI 1.28–1.63] and 62% [1.44–1.82], respectively) regardless of BP-treatment. Conclusions: Legacy effect of BP-lowering amlodipine-based treatment is primarily mediated by the reduction in BPV. Those with high mean SBP (>140) and/or high BPV (>15) and should be targeted to mitigate long-term CV risk.