Key Points
- The ESPRIT trial assessed whether the efficacy and safety of intensive blood pressure (BP) varies across frailty status compared to control.
- In this open-label trial, 11,255 patients were randomized into intensive vs standard blood pressure treatment groups. Both groups were followed over a median of 3.4 years.
- The findings support the adoption of intensive blood pressure control, targeting a systolic BP below 120 mmHg, in hypertensive patients at high cardiovascular risk, regardless of frailty status.
A post-hoc analysis of the ESPRIT trial was presented at ACC2025 on Monday, March 31, 2025. Although SPRINT and ACCORD BP trials suggest benefit from intensive BP control for patients with and without frailty, the impact of frailty on the effectiveness and safety of intensive blood pressure control remains unclear. Most guidelines do not give numerical targets in frail older adults while they continue to suffer the risk of polypharmacy. This study sought to fill the gap by examining how frailty status affects the outcomes of intensive BP management.
The Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs (ESPRIT) trial was a multi-center, open-label, randomized controlled trial to compare the efficacy and safety of intensive BP lowering strategy (Systolic BP target <120 mm Hg) and standard BP lowering strategy (Systolic BP target <140 mm Hg). Participants at least 50 years old with baseline systolic BP within 130 to 180 mm Hg at high CV risk, defined by established CV diseases or 2 major CV risk factors, were enrolled. The primary outcome was a composite CV outcome of myocardial infarction, coronary or non-coronary revascularization, hospitalization or emergency department visit from new-onset heart failure or acute decompensated heart failure, stroke, or death from CV diseases. Secondary outcomes included components of the primary composite outcome, all-cause death, a composite of the primary outcome or all-cause death, kidney outcomes, as well as cognitive outcomes. Safety outcomes included hypotension, electrolyte abnormalities, injurious falls, and acute kidney injury.
A total of 11,255 high cardiovascular risk patients were randomized into an intensive treatment group with a target systolic blood pressure of ≤120 mmHgor standard treatment group with a target systolic blood pressure of ≤140 mmHg. A frailty index (FI) was constructed and classified using a composite of Rockwood cumulative deficit, EQ-5D, medical history, lifestyle questionnaire, laboratory tests, physical examination and cognitive screening. The patients were sub-categorized into non-frail (FI ≤ 0.21), moderately frail (FI 0.211-0.310) and severely frail (FI ≥0.311) groups. At baseline, 26.3% of the participants were non-frail, 50.6% were moderately frail whereas 23.1% were severely frail.
The baseline characteristics of the two groups were largely comparable. However, the severely frail patient category exhibited a slightly higher prevalence of older individuals, elevated overall blood pressure readings, and a longer median duration of hypertension. Additionally, this group had a greater proportion of patients with diabetes, prior stroke, myocardial infarction, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), chronic kidney disease (CKD), and coronary heart disease (CHD). In contrast, the non-frail patient category consisted of a relatively higher proportion of females and demonstrated an increased prevalence of atrial fibrillation and dyslipidemia compared to groups with greater frailty indices.
Statistical analysis revealed no significant difference between intensive and standard treatment in relation to cardiovascular events or serious adverse events. Notably, patients in the standard treatment group attained target blood pressure more frequently and at an earlier stage than those in the intensive treatment group. Furthermore, blood pressure readings remained stable across all frailty levels within the treatment groups, with no significant variations observed.
As this is a post-hoc analysis, there is an intrinsic risk of bias, including the potential for Type I error. Additionally, the limited number of safety outcomes raises the possibility that the observed significant differences between the study arms may be attributable to random errors.
Dr. Li Shitian MD, from Fuwai Hospital of National Center for Cardiovascular Diseases (NCCD) China concluded on behalf of the ESPRIT investigators that “Treating 1000 participants in severe-frail group with intensive BP control for 3.4 years would prevent 30 MACE, 21 all-cause death, induce 16 composite kidney outcomes and 7 injurious falls”. The team maintains the narrative that their findings support adopting the intensive BP control strategy targeting SBP below 120 mmHg in hypertensive patients with high cardiovascular risk regardless of frailty status.