Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension

Abstract

Hypertension is a very common disease in the elderly (aged ≥65 years). 1 More than 50% of the elderly population has hypertension, 2 especially systolic hypertension, which arises primarily due to age-related changes in the arterial structure of large arteries, contributing to the large artery stiffness. 3 These changes lead to loss of arterial elasticity, 4 resulting in elevated systolic blood pressure (SBP) and widened pulse pressure (PP; difference between SBP and diastolic blood pressure [DBP]). 1 Studies have shown that elevated SBP has a stronger association with adverse cardiovascular (CV) outcomes than elevated DBP in the elderly. 1,5,6 Furthermore, lowering of SBP has been shown to reduce the risk of CV events in elderly patients. 7 A strong association between hypertension and CV events has been reported in Asian population. 8 Olmesartan is one of the most widely prescribed angiotensin II receptor blockers (ARBs) for the treatment of systolic hypertension in elderly patients, 10 including Asians. 11 Despite the available antihypertensive treatments, blood pressure (BP) control is poor in Asian patients. 12 In addition, SBP is considered more difficult to control than DBP, particularly in elderly patients, 13,14 which further suggests the need to develop more effective treatments to target the underlying causes of systolic hypertension in this population.BP is modulated by counter-regulatory neurohormonal interactions between natriuretic peptides, the sympathetic nervous system, and the renin-angiotensin-aldosterone system. 15 Natriuretic peptide levels can be enhanced by inhibiting the enzyme neprilysin, which catalyzes the degradation of multiple vasoactive peptides in the CV system, including natriuretic peptides. 16,17 Blockade of the angiotensin receptor reduces sodium and water retention and inhibits cardiac hypertrophy and remodeling (arterial stiffness). 18,19 Considering the age-related changes to arteries underlying OBJECTIVESystolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (≥65 years) with systolic hypertension. METHODSIn this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4. At week 10, for patients with blood pressure (BP) >140/90 mm Hg, the doses were up-titrated to sacubitril/valsartan 400 mg or olmesartan 40 mg. The primary assessment was superiority of sacubitril/valsartan vs. olmesartan in reducing office mean sitting (ms) systolic BP (msSBP) from baseline at week 10. Secondary efficacy assessments included changes from baseline in ms diastolic BP (msDBP), ms pulse pressure (msPP), 24-hour mean ambulatory (ma) BP (maBP), and maPP at week 10; msBP and msPP at weeks 4 and 14. RESULTSOverall, 588 patients were randomized (...

Expert panel consensus recommendations for ambulatory blood pressure monitoring in Asia: The HOPE Asia Network

“…ABPM studies showed that sacubitril/valsartan effectively reduced 24‐hour BP, including nocturnal BP, in both Western and Asian patients with hypertension . Data show that Asian patients with hypertension may respond particularly well to this agent …”

Effects of LCZ696 (Sacubitril/Valsartan) on Blood Pressure in Patients with Hypertension: A Meta-Analysis of Randomized Controlled Trials

“…Two studies [6,9] reported SBP and DBP in LCZ696 100 mg and ARBs. Compared with ARBs, LCZ696 100 mg caused a significant reduction in SBP (MD -1.58 mm Hg, 95% CI -2.09 to -1.07, p < 0.05) and DBP (MD -0.66 mm Hg, 95% CI -0.98 to -0.33, p < 0.05) (Fig.…”

“…Six studies [6,[9][10][11][12][13] reported SBP, DBP, 24 h ASBP, and 24 h ADBP in LCZ696 200 mg and ARBs. Compared with ARBs, LCZ696 200 mg caused a significant reduction in SBP (MD -4.94 mm Hg, 95% CI -6.54 to -3.35, p < 0.05), DBP (MD -2.24 mm Hg, 95% CI -2.74 to -1.75, 3).…”

“…Twelve studies reported SBP and DBP [6][7][8][9][10][11][12][13][14][15][16][17]. Eight studies reported 24 h ASBP and 24 h ADBP [6][7][8][9][10][11][12][13].…”

Known–Unknowns in Geriatric Cardiology

“…Sacubitril/valsartan could reduce dyspnea and blood pressure, and improved the left ventricular pathologic changes as assessed by echocardiography. Another study [103] reported the effect of sacubitril/valsartan versus olmesartan in 588 hypertensive Asian patients with a mean age of 70.7 years. Sacubitril/valsartan exhibited greater lowering of blood pressure compared to olmesartan, and no relevant side-effects were reported.…”