Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website http://www.cardiologyres.org

Original Article

Volume 10, Number 1, February 2019, pages 24-33

Anti-Hypertensive Effect of Sacubitril/Valsartan: A Meta-Analysis of Randomized Controlled Trials

Figure 2. Mean reduction (mm Hg) in sitting systolic blood pressure (msSBP) in hypertensive patients treated with sacubitril/valsartan compared to ARB-treated controls. (a) In the control group olmesartan was used as comparator drug. (b) In the control group valsartan was used as comparator drug. pts: patients; st.dev: standard deviation; ctrl: controls; ARBs: angiotensin receptor blockers; CI: confidence interval.

Figure 3. Mean reduction (mm Hg) in sitting diastolic blood pressure (msDBP) in hypertensive patients treated with sacubitril/valsartan compared to ARB-treated controls. (a) In the control group olmesartan was used as comparator. (b) In the control group valsartan was used as comparator. pts: patients; st.dev: standard deviation; ctrl: controls; ARBs: angiotensin receptor blockers; CI: confidence interval.

Figure 4. Mean sitting blood pressures (msSBP and msDBP) in sacubitril/valsartan-treated patients vs. ARB-treated controls.

Figure 5. Mean reduction (mm Hg) in ambulatory systolic blood pressure (maSBP) in hypertensive patients treated with sacubitril/valsartan compared to ARB-treated controls. (a) In the control group olmesartan was used as comparator. (b) In the control group valsartan was used as comparator. pts: patients; st.dev: standard deviation; ctrl: controls; ARBs: angiotensin receptor blockers; CI: confidence interval.

Figure 6. Mean reduction (mm Hg) in ambulatory diastolic blood pressure (maDBP) in hypertensive patients treated with sacubitril/valsartan compared to ARB-treated controls. (a) In the control group olmesartan was used as comparator. (b) In the control group valsartan was used as comparator. pts: patients; st.dev: standard deviation; ctrl: controls; ARBs: angiotensin receptor blockers; CI: confidence interval.

Figure 7. Adverse events (AEs) in sacubitril/valsartan-treated patients vs. ARB-treated controls. (a) In the control group olmesartan was used as comparator. (b) In the control group valsartan was used as comparator. pts: patients; ctrl: controls; ARBs: angiotensin receptor blockers; CI: confidence interval.

**Table 1.** Main Features of Studies Incorporated in the Meta-Analysis
Study	Williams et al, 2017 [15]	Supasyndh et al, 2017 [16]	Schmieder et al, 2017 [17]	Wang et al, 2017 [14]	Izzo et al, 2017 [13]
(a) Olmesartan was used as a comparator drug. (b) Valsartan was used as a comparator drug. DB: double blind; RCT: randomized controlled trial; ARB: angiotensin receptor blocker; QD: every day; BP: blood pressure.
Type of study	Monotherapy only, drug comparison, multicenter	Monotherapy only, drug comparison, multicenter	Monotherapy or combination therapy with amlodipine, drug comparison, multicenter	Monotherapy only, drug comparison, multicenter	Monotherapy only, drug comparison, multicenter
Blind	DB	DB	DB	DB	DB
RCT	Yes	Yes	Yes	Yes	Yes
Comparisons	Sacub/v vs. olmesartan	Sacub/v vs. olmesartan	Sacub/v vs. olmesartan	Sacub/v vs. valsartan	Sacub/v vs. valsartan
Number of patients	454	588	114	72	285
Study duration (weeks)	12 - 52	14	12 - 52	4	8
Doses of sacubitril/valsartan per day	200 or 400 mg	100, 200 or 400 mg	200 or 400 mg plus optional amlodipine, up to 10 mg QD, only if needed for BP control	400 mg	400 mg
Doses of ARB per day	20 or 40 mg (a)	10, 20 or 40 mg (a)	20 or 40 mg (a) plus optional amlodipine, up to 10 mg QD, only if needed for BP control	320 mg (b)	320 mg (b)

Table 1. Main Features of Studies Incorporated in the Meta-Analysis

Study

Williams et al, 2017 [15]

Supasyndh et al, 2017 [16]

Schmieder et al, 2017 [17]

Wang et al, 2017 [14]

Izzo et al, 2017 [13]

(a) Olmesartan was used as a comparator drug. (b) Valsartan was used as a comparator drug. DB: double blind; RCT: randomized controlled trial; ARB: angiotensin receptor blocker; QD: every day; BP: blood pressure.

Type of study

Monotherapy only, drug comparison, multicenter

Monotherapy or combination therapy with amlodipine, drug comparison, multicenter

Monotherapy only, drug comparison, multicenter

Blind

RCT

Yes

Comparisons

Sacub/v vs. olmesartan

Sacub/v vs. valsartan

Number of patients

454

588

114

285

Study duration (weeks)

12 - 52

Doses of sacubitril/valsartan per day

200 or 400 mg

100, 200 or 400 mg

200 or 400 mg plus optional amlodipine, up to 10 mg QD, only if needed for BP control

400 mg

Doses of ARB per day

20 or 40 mg (a)

10, 20 or 40 mg (a)

20 or 40 mg (a) plus optional amlodipine, up to 10 mg QD, only if needed for BP control

320 mg (b)

**Table 2.** Several Anthropometric Measures Are Reported in the Table, Along With Baseline Blood Pressure Levels and Programmed Study Outcomes
Study	Williams et al, 2017 [15]	Supasyndh et al, 2017 [16]	Schmieder et al, 2017 [17]	Wang et al, 2017 [14]	Izzo et al, 2017 [13]
sacub val: sacubitril/valsartan; SD: standard deviation; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; AEs: adverse events; NA: not available; msSBP: mean reduction in sitting systolic blood pressure; msDBP: mean reduction in sitting diastolic blood pressure; maSBP: mean reduction in ambulatory systolic blood pressure; maDBP: mean reduction in ambulatory diastolic blood pressure.
Age (years) (sacub val/controls, mean ± SD)	68.2 ± 5.73/67.2 ± 5.97	70.5 ± 4.67/70.9 ± 4.67	60.5 ± 7.8/59.2 ± 13.1	55.7 ± 12.5/58.9 ± 7.5	Mean 61
Men (sacub val/controls, %)	52/52.4	48/52.1	64.9/70.2	64/64	NA
BMI (sacub val/controls, kg/m², mean ± SD)	27.4 ± 4.5/28.1 ± 4.9	23.4 ± 4.15/23.6 ± 3.15	29.1 ± 5.6/29.6 ± 4.2	25.4 ± 5.1/26.7 ± 2.3	Mean 27.9
Baseline SBP (sacub val/controls, mm Hg, mean ± SD)	160.4 ± 12.32/160.8 ± 15.6	159.5 ± 8.41/158.0 ± 6.95	160.3 ± 7.2/161.9 ± 8.2	158.5 ± 8.6/159.5 ± 7.2	NA
Baseline DBP (sacub val/controls, mmHg, mean ± SD)	85.8 ± 8.62/85.8 ± 8.6	85.5 ± 4.43/85.9 ± 6.7	86.7 ± 7.5/87 ± 5	85.2 ± 5.6/86.0 ± 5.3	NA
Outcomes	msSBP, msDBP, maSBP, maDBP, AEs	msSBP, msDBP, maSBP, maDBP, AEs	msSBP, msDBP	msSBP, msDBP, maSBP, maDBP, AEs	msSBP, msDBP, AEs

Table 2. Several Anthropometric Measures Are Reported in the Table, Along With Baseline Blood Pressure Levels and Programmed Study Outcomes

Study

Williams et al, 2017 [15]

Supasyndh et al, 2017 [16]

Schmieder et al, 2017 [17]

Wang et al, 2017 [14]

Izzo et al, 2017 [13]

sacub val: sacubitril/valsartan; SD: standard deviation; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; AEs: adverse events; NA: not available; msSBP: mean reduction in sitting systolic blood pressure; msDBP: mean reduction in sitting diastolic blood pressure; maSBP: mean reduction in ambulatory systolic blood pressure; maDBP: mean reduction in ambulatory diastolic blood pressure.

Age (years) (sacub val/controls, mean ± SD)

68.2 ± 5.73/67.2 ± 5.97

70.5 ± 4.67/70.9 ± 4.67

60.5 ± 7.8/59.2 ± 13.1

55.7 ± 12.5/58.9 ± 7.5

Mean 61

Men (sacub val/controls, %)

52/52.4

48/52.1

64.9/70.2

64/64

BMI (sacub val/controls, kg/m², mean ± SD)

27.4 ± 4.5/28.1 ± 4.9

23.4 ± 4.15/23.6 ± 3.15

29.1 ± 5.6/29.6 ± 4.2

25.4 ± 5.1/26.7 ± 2.3

Mean 27.9

Baseline SBP (sacub val/controls, mm Hg, mean ± SD)

160.4 ± 12.32/160.8 ± 15.6

159.5 ± 8.41/158.0 ± 6.95

160.3 ± 7.2/161.9 ± 8.2

158.5 ± 8.6/159.5 ± 7.2

Baseline DBP (sacub val/controls, mmHg, mean ± SD)

85.8 ± 8.62/85.8 ± 8.6

85.5 ± 4.43/85.9 ± 6.7

86.7 ± 7.5/87 ± 5

85.2 ± 5.6/86.0 ± 5.3

Outcomes

msSBP, msDBP, maSBP, maDBP, AEs

msSBP, msDBP

msSBP, msDBP, maSBP, maDBP, AEs

msSBP, msDBP, AEs