Treatment escalation beyond triple therapy in patients with resistant hypertension: a population-based observational cohort study from UK healthcare records

Background/Introduction Many patients do not achieve target blood pressure (BP) and develop resistant hypertension (rHTN), despite stepwise escalation guidelines. Real world data for post-triple-therapy treatment patterns are limited, and it remains unclear whether prescribing aligns with guideline recommendations or how treatment patterns evolve in routine clinical care. Purpose To describe patient profiles and triple-drug regimens, quantify escalation to a fourth agent, and assess fourth-drug prescribing, persistence, and adherence. Methods A retrospective cohort study was conducted using linked UK primary and secondary care data (1/1/2017-31/3/2023). Adults with diagnosed hypertension receiving ≥3 antihypertensive drug classes, including a thiazide-like diuretic, were included. Index was the first BP ≥30 days after triple-drug regimens and rHTN was defined as BP ≥140/90 mmHg at index. Patients with end-stage kidney disease or heart failure history were excluded. We described patient characteristics, latest triple therapies (from 60 days before diagnosis to end of follow-up), and the proportion directly escalating from three to four classes post index. Persistence (time to discontinuation accounting for gaps, loss to follow-up/death) and adherence (proportion of days covered [PDC], good adherence if >80%) to the fourth agent were assessed over 6–24 months from prescription records. Results Among 11,876 patients on triple therapy, 10,371 (87%) had rHTN; mean age was 60 years, 46% were women, and comorbidities included chronic kidney disease (40%), atrial fibrillation (4%), and stroke (6%) (Table 1). The most frequent triple therapy was RAAS blockers (angiotensin-converting enzyme inhibitors [ACEi] or angiotensin receptor blockers [ARB]) + calcium channel blockers (CCB) + thiazide-like diuretics, accounting for 64% of regimens; and 693 (7%) escalated directly to a fourth class. The most common fourth line agents added were alpha-blockers (36%), beta-blockers (19%), followed by CCB (10%) and direct vasodilators (10%); mineralocorticoid receptor antagonists (MRA) use was 7% (Figure 1A). Persistence was poor among all drug classes apart from diuretics at 61% and 65% by 12 and 24 months. Other drug classes were predominantly discontinued by 12 and 24 months, respectively. Across drug classes, fewer than half of patients achieved good adherence at 6 months, and adherence decreased further by 12 months (Figure 1B). Conclusion(s) Resistant HTN remains prevalent, yet treatment intensification is infrequent. Despite guideline recommendations and trial evidence supporting their superiority, MRAs do not represent the common choice, and persistence and adherence to the fourth-line therapy are suboptimal. These results highlight the need to understand barriers to treatment escalation and to identify strategies or fourth-line options that can be more widely adopted in routine care and non-specialist settings.