Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction (HFpEF)

Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction

• majority of patients with HFpEF have a history of hypertension
• hypertension is often difficult to control in this patient population despite use of multiple antihypertensive medications
• resistant hypertension is therefore common in patients with HFpEF (1)
• resistant hypertension
  • is formally defined as blood pressure persistently above target, despite the use of three antihypertensive agents of different classes, including an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), a calcium channel blocker, and a diuretic, although there is some variation between USA and European guidelines
• post-hoc analysis of the PARAGON-HF trial investigated the association between apparent resistant hypertension and outcomes in HFpEF and studied the effect of neprilysin inhibition on blood pressure in patients with HFpEF and apparent resistant hypertension
  • 'apparent mineralocorticoid receptor antagonist (MRA) - resistant' hypertension was defined as systolic blood pressure >=140 mmHg (>= 135 mmHg if diabetes) despite the above treatments and an MRA
  • primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes
    • overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension
    • rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6-19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7-14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05-1.57)
    • reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril-valsartan vs. valsartan in patients with apparent resistant hypertension [-4.8 (-7.0 to -2.5) and 3.9 (-6.6 to -1.3) mmHg] and apparent MRA-resistant hypertension [-8.8 (-14.0 to -3.5) and -6.3 (-12.5 to -0.1) mmHg]
    • proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril-valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30-2.43]
    • in patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18-5.89)
• Conclusion:
  • post-hoc analysis of PARAGON-HF suggests that sacubitril/valsartan is an effective and safe treatment of apparent resistant hypertension and apparent MRA-resistant hypertension

Reference:

• Jackson AM, Jhund PS, Anand IS et al. Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction Eur Heart J. 2021 Aug 15;ehab499. doi: 10.1093/eurheartj/ehab499.