Time to Benefit Following Intensive BP Reduction in Adults Aged 60 Years and Older

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Intensive blood pressure (BP) control in older adults with hypertension may be appropriate for those with life expectancy of ≥3 years but the risks may be too great for those expected to live for less than 1 year, conclude authors of a new study published in JAMA Internal Medicine.

As background for their study, the research team, led by Zhixin Jiang, PhD, department of cardiology, The First Affiliated Hospital of Nanjing Medical University, China, first point to meta-analyses showing the benefits, ie, improved cardiovascular (CV) outcomes, of tight control of systolic BP in persons with hypertension aged ≥65 years and highlight findings from a large trial that demonstrated improved CV results among patients aged 60 to as old as 80 years who achieved SBP targets 110 – 130 mm Hg vs the more standard target of 130 – 150 mm Hg.

The difficulty in extrapolating those findings to the general older adult public, the authors point out, is the large heterogeneity in CV risk in the population aged ≥60 years which makes it essential for clinicians to weigh for each patient the risks (eg, falls, syncope, acute kidney injury) of reaching ideal SBP targets.

Most important, because harms of treatments can occur immediately, but benefits emerge over time, treatment decisions need to account for the lag in time to benefit (TTB) so that patients with limited life expectancy are not exposed to the potential harms of preventive treatment “with little chance of benefit,” the authors write.

Harms of treatment can occur immediately, but benefits emerge over time.

Given the paucity of data on the subject, the authors set out to estimate the time needed to potentially derive clinical benefit from intensive BP treatment in patients aged ≥60 years.

Jiang et al conducted a secondary analysis of randomized clinical trials, conducting a PubMed search for clinical trials of intensive BP in older adults with hypertension published through October 15, 2021. If original study data were not available, investigators reconstructed them from the number of patients at risk and the Kaplan-Meier graph.

The primary outcome was time-to-first major adverse cardiovascular event (MACE) which was defined similarly by the original trials as a composite of cardiovascular outcomes (myocardial infarction, stroke, and CV death), the investigators noted.

The research team initially identified 85 clinical trials extracted from 7 systematic reviews and meta-analyses. The final analysis was based on 6 trials. The final cohort numbered 27 414 participants, of which 56.3% were women and with a mean age of 70 years.

The authors found that intensive BP treatment with a SBP target <140 mm Hg was significantly associated with a 21% reduction in MACE (hazard ratio [HR], 0.79; 95% CI, 0.71 - 0.88; P <.001).

Although there was no statistically significant association for MACE between target SBP <140 mm Hg vs SBP <150/160 mm Hg (HR, 0.92; 95% CI, 0.69- 1.22; P =.57), investigators did find a significant treatment benefit in subgroups of:

• Target SBP <130 mm Hg vs SBP <150/140 mm Hg (HR, 0.69; 95% CI, 0.57-0.84; P <.001)
• Target SBP <120 mm Hg vs SBP <140 mm Hg (HR, 0.82; 95% CI, 0.71-0.94; P =.005)

Time to benefit analysis

When they analyzed data to determine the TTB at different clinically meaningful thresholds, the authors found that 9.1 (95% CI, 4.0 - 20.6) months were needed to prevent 1 MACE per 500 patients with the intensive BP treatment (absolute risk reduction [ARR], 0.002). Similarly, they found 19.1 (95% CI, 10.9 - 34.2) months were required to avoid 1 MACE per 200 (ARR =.005) patients and 34.4 (95% CI, 22.7 - 59.8) months to avoid 1 MACE per 100 (ARR =.01) patients.

Investigators noted the TTB to specific ARR threshold varied across different subgroups, with “little changes compared with the overall estimate.”

They found the TTB was consistently higher in the subgroup of target SBP <120 mm Hg vs SBP <140 mm Hg compared with that of target SBP <130 mm Hg vs <150/160 mm Hg.

The authors say that, to their knowledge, this is the “first study to use robust quantitative methods” to estimate the TTB for prevention of CV events using intensive BP control in older adults.

They also stress that the TTB results of their study provide a “global estimate” for prevention with intensive BP control and that, as recommended by contemporary clinical BP guidelines, “clinical judgment, patient preference, and a team-based approach to assess risk–benefit is reasonable for decisions regarding intensity of BP lowering and choice of antihypertensive drugs for older adults.”

Reference: Chen T, Shao F, Chen K, et al. Time to clinical benefit of intensive blood pressure lowering in patients 60 years and older with hypertension: a secondary analysis of randomized clinical trials. JAMA Intern Med. Published online May 9, 2022. doi:10.1001/jamainternmed.2022.1657