Two trends stand out.
The first trend is using low-dose triple and quadruple single-pill combinations as initial therapy. The idea is simple: using three or four agents at a quarter or half dose lowers blood pressure more than one agent at a full dose. Plus, it causes fewer side effects. For older patients with multiple comorbidities the benefits are clear. Fewer tablets, lower doses, and a simpler routine are important advantages. This is especially true when polypharmacy is a concern.
The data…
A 2024 Lancet trial found that a low-dose mix of telmisartan, amlodipine, and indapamide lowered systolic pressure by 2.5 to 5.7 mmHg more than dual therapy - clinical control rates hit 74%.
A second Lancet analysis of the same combination, this time against placebo as initial treatment, confirmed significant reductions from baseline.
The QUARTET USA trial tested a quadruple quarter-dose pill and found further reductions over standard monotherapy with good tolerability.
A Chinese phase III trial showed that one pill with perindopril, indapamide, and amlodipine worked as well as taking each drug separately. The researchers confirmed this with lasting control at six months.
None of these specific formulations are available in the UK yet; however, the path is clear: take fewer pills, use lower doses and combine treatments sooner. For patients, adherence is a key reason for poor control.
The second trend represents a completely new territory. Two new drug classes are showing Phase III data for resistant hypertension. This is important due to the ineffectiveness of current treatments for this population.
Aprocitentan is a dual endothelin receptor antagonist. The PRECISION trial found that patients on three or more antihypertensives had a systolic blood pressure about 4 mmHg lower than those on placebo after four weeks. Subgroup analyses found a significant benefit for patients aged 75 and older, as well as for those with CKD. These groups are common in older patients with resistant hypertension. Oedema and fluid retention were more common in older patients in the trial. This is important to consider for this age group.
Baxdrostat and lorundrostat are aldosterone synthase inhibitors, a completely different mechanism. Recent phase 3 data for baxdrostat showed a 9 to 10 mmHg drop in systolic pressure compared to placebo. Researchers saw this effect in cases of uncontrolled and resistant hypertension. The Launch-HTN trial of lorundrostat reported similar results. The key monitoring concern with this class is hyperkalaemia, a particularly relevant consideration in older patients with CKD or those already on renin-angiotensin system agents.
These reductions are modest in absolute terms. In patients on three or four medications who still exceed targets, an extra 4 to 10 mmHg matters. It can mean the difference between controlled and uncontrolled disease. We still lack long-term cardiovascular outcome data for these newer agents. This gap is significant. Right now, the evidence supports short-term blood pressure lowering. We still need to show whether that translates into fewer strokes and heart attacks.
For UK primary care, the practical implications are still over the horizon. None of these new agents are approved by NICE or listed on NHS formularies right now. But the pipeline is worth watching. Patients on your QOF register with resistant hypertension are the focus for these drugs. They remain above target even after using four agents. When they arrive, the referral conversation with secondary care may look quite different.
These articles report on published research. It does not constitute medical advice.
