Background: Isolated Systolic Hypertension (ISH), defined as elevated systolic blood pressure (SBP) with normal diastolic blood pressure (DBP), is prevalent among elderly patients and is difficult to control due to associated comorbidities. It significantly increases the risk of cardiovascular events, like stroke and heart failure. Although excessively low DBP has been associated with increased cardiovascular risks and mortality, lowering of SBP is strongly linked to improved outcomes, irrespective of reductions in DBP in patients with ISH.. Thus, in this analysis, it was assessed if aprocitentan, could effectively reduce SBP while maintaining DBP above clinically acceptable levels (i.e. 60 mmHg) in RHT patients with BP resembling ISH despite standard 3-drug antihypertensive therapy. Methods: In PRECISION, patients were included based on Sitting SBP (SiSBP) ≥140 mmHg, with no threshold set for Sitting DBP (SiDBP). Therefore, 57% of the patients had BP resembling ISH (SiSBP≥140 mmHg with an SiDBP<90 mmHg). In Part 1 of PRECISION, patients were randomized to receive aprocitentan (12.5 mg or 25 mg daily) or placebo for 4 weeks. Here changes from baseline to Week 4 in SiSBP and SiDBP assessed by automated office BP measurement (AOBPM) were analyzed in patients with BP resembling ISH. Results: In the ISH-like group (n=422), the baseline mean SiSBP and SiDBP were 156.9 mmHg and 83.9 mmHg, respectively. They presented with a higher mean age (mean SD; 65.5 9.1 vs 56.6 10.4 years) and a higher proportion of patients with CKD Stage 3-4 (30% vs 12%) compared with the non-ISH group. At Week 4, the aprocitentan 12.5mg and 25 mg arms showed a mean reduction (SD) in SiSBP of 13.8 mmHg (15.3) and 13.7 mmHg (12.5) vs 8.5 mmHg (14.2) and in SiDBP of 8.1 mmHg (9.1) and 7.9 mmHg (8.0) vs 2.8 mmHg (8.3) in the placebo arm in the ISH-like group. Thus, at Week 4, patients with ISH-like BP experienced a substantial reduction in SiSBP and SiDBP, while maintaining SiDBP above 70 mmHg (Table 1), which is within the clinically optimal range (60 to 80 mmHg). No new safety signals were identified in this subgroup. Conclusions: Aprocitentan led to a substantial reduction in systolic BP in patients with BP resembling ISH without any evidence of adverse events. It reduced DBP to achieve clinically optimal values associated with the lowest levels of cardiovascular risks. Thus, it can be an effective and well-tolerated therapeutic option for patients with ISH-like characteristics.
Flack et al. (Mon,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: