Reducing Antihypertensive Therapy in Nursing Home Residents – Insights from the RETREAT-FRAIL Study

Older patients with hypertension are at high risk of cardiovascular complications, making appropriate antihypertensive therapy especially important in this population. However, randomized clinical trials often exclude patients with marked frailty, as adverse effects of antihypertensive therapy are more common in these individuals.

Several observational studies have shown that in frail patients, low blood pressure is associated with increased cardiovascular morbidity and mortality, particularly in those receiving antihypertensive therapy. In the observational PARTAGE study, which included nursing home residents over 80 years of age with hypertension, overall mortality was found to be twice as high among participants with systolic blood pressure below 130 mmHg who were taking more than one antihypertensive, compared to other participants.

This finding from the PARTAGE study raises an important question about the management of hypertension in older patients with pronounced frailty. The latest European hypertension guidelines emphasize the need to tailor therapy to the degree of frailty and recommend considering gradual reduction of antihypertensive therapy in patients with low blood pressure. However, evidence on the benefits and risks of discontinuing antihypertensive drugs in older adults remains limited. There is consensus that clinical research should focus on populations where uncertainty about the risks and benefits of antihypertensive therapy is greatest, such as frail individuals, the very elderly, and those receiving multiple medications simultaneously.

Recently, the results of the RETREAT-FRAIL (Reduction of Antihypertensive Treatment in Frail Patients) study were published. This was a pragmatic, interventional, randomized trial that evaluated the effect of protocol-guided, stepwise reduction of antihypertensive therapy, compared with usual care, on overall mortality among nursing home residents aged 80 years or older with pronounced frailty, systolic blood pressure below 130 mmHg, and treatment including at least two antihypertensives.

In this multicenter, randomized, controlled trial conducted in France, participants were randomized in a 1:1 ratio to either protocol-based gradual reduction of antihypertensive therapy or usual care (control group). Patients were followed for up to 4 years. The primary outcome was death from any cause. Secondary outcomes included changes in the number of antihypertensive medications from baseline to final visit and changes in systolic blood pressure during follow-up.

Results of the RETREAT-FRAIL Study

A total of 1,048 patients were randomized: 528 to the antihypertensive reduction group and 520 to the control group. The estimated median follow-up was 38.4 months. Between baseline and the final visit, the mean (±SD) number of antihypertensives decreased from 2.6±0.7 to 1.5±1.1 in the reduction group and from 2.5±0.7 to 2.0±1.1 in the control group. The adjusted mean difference between groups (reduction group minus control group) in systolic blood pressure change during follow-up was 4.1 mmHg (95% confidence interval [CI], 1.9 to 5.7).

All-cause mortality occurred in 326 patients (61.7%) in the reduction group and 313 patients (60.2%) in the control group (adjusted hazard ratio 1.02; 95% CI, 0.86 to 1.21; P=0.78). There were no significant differences in adverse events between the groups.

Conclusion

In frail nursing home residents over 80 years of age who were taking more than one antihypertensive and had systolic blood pressure below 130 mmHg, a strategy of gradual reduction of antihypertensive therapy did not result in lower overall mortality compared with usual care.

In conclusion, this trial did not confirm the authors’ hypothesis that stepwise reduction of antihypertensive therapy in this population would lead to a 25% reduction in overall mortality compared with usual care.

Adapted from: Benetos A, et al; RETREAT-FRAIL Study Group. Reduction of Antihypertensive Treatment in Nursing Home Residents. N Engl J Med. 2025 Aug 29. doi: 10.1056/NEJMoa2508157.