S-Amlodipine: An Isomer with Difference—Time to Shift from Racemic Amlodipine

Table 1

Randomized controlled trials of S-amlodipine in hypertension.

Author (year)	Country	S-AM; (mg)	Comparator; (mg)		Duration; (weeks)	Antihypertensive efficacy	AEs
Monotherapy Studies (n = 16)
Liu et al. (2001) [44]	China	2.5	Amlo (5)	30/30	4	Equivalent	NA
Fang (2002) [45]	China	2.5	Amlo (5)	140/140	40	Equivalent	NR
Cheng et al. (2002) [46]	China	2.5–5	Amlo (5–10)	60/60	5	Equivalent	No difference, milder with S-AM
Hiremath and Dighe (2002) [47]	India	2.5	Amlo (5)	25/25	6	Mean change of SBP/DBP (S-AM Vs Amlo); Standing: −24.21/−13.08 vs −21.6/−13.44; Supine: −27.13/−14.17 vs −22.04/−13.68; Sitting: −26.86/−14.17 vs −23.06/−14.28	None
Kerkar (2003) [48]	India	2.5	Amlo (5)	25/25	6	Mean change of SBP/DBP (S-AM Vs Amlo); Standing: −22.6/−12.72 vs −21.96/−13.24; Supine: −22.84/−13.18 vs −22.32/−13.4; Sitting: −20.16/−13.76 vs −22.24/−15.0	None
Pathak et al. (2004) [49]	India	2.5	Amlo (5)	97/91	6	Mean change of SBP/DBP (S-AM Vs Amlo); Standing: −19.22/−13.63 vs −19.14/−12.76; Supine: −19.69/−13.95 vs −19.24/−13.33; Sitting: −19.87/−14.31 vs −19.24/−13.05	None
Zhang (2006) [50]	China	2.5–5	Amlo (5–10)	36/36	8	S-AM: 165.30/98.22 to 132.70/81.87; Amlo: 164.30/99.30 to 134.10/85.61	Number: 1 vs 6
Bae et al. (2008) [51]	Korea	2.5	Amlo (5)	58/60	8	SBP: −24.27 ± 11.55 vs −25.24 ± 12.47; DBP: −14.73 ± 8.9 vs −14.56 ± 9.28; S-AM non-inferior to Amlo	No significant differences
Zhu et al. (2008) [52]	China	2.5–5	Amlo (5–10)	44	8	Mean change in; SBP: 156.26 to 131.50 vs 158.23 to 131.74; DBP: 98.48 to 83.28 vs 99.18 to 83.19	None
Youn et al. (2010) [17]	Korea	2.5	Lercani	32/29	8	Mean change; sSBP: −20.5 ± 13.6 vs −19.93 ± 14.5; sDBP: −14.03 ± 8.07 vs −12.93 ± 8.68	None
Kim et al. (2011) [19]	Korea	2.5	Rami (2.5–5)	68/70	8	Mean change; SBP: −18.1 ± 7.91 vs −14.3 ± 11.96; (); DBP: −12.7 ± 7.02 vs −9.6 ± 7.38; (); BP normalization rate: 81.3% vs 61.4% ()	5.8% vs 14.2% ()
Shengye (2012) [53]	China	2.5–5	Amlo (5–10)	90/90	8	Equivalent	Milder with S-AM
Oh et al. (2012) [15]	Korea	2.5–5	Amlo (5–10)	17/17	12	Mean change; sSBP: −21.82 ± 8.76 vs −26.82 ± 11.89 (); sDBP: −14.71 ± 6.94 vs −10.88 ± 5.81 ()	Significant improvement in ankle edema with S-AM (AFV difference: −70.26 mL, )
Zhao (2013) [54]	China	NA	Nifed-SR	61/61	NA	Significant reduction in BP in both groups; Overall response rate: 91.8% vs 80.33% ()	Lower with S-AM: 6.56% vs 18.03% ()
Parvathi et al. (2014) [55]	India	2.5	Amlo (5)	54/54	12	SBP change: −32.4 vs −26.9; DBP change: −13.4 vs −12.0	Edema significantly lower with S-AM: mean change AC: 0.26 vs 0.02 ()
Chen et al. (2017) [20]	China	2.5	S-AM (5)	263/260	8	SBP: 6.0 vs 8.1 (); DBP: 3.8 vs 4.7 (); Target BP achievement: SBP: 81.8% vs 90.8%; DBP: 84.0% vs 94.2%; SBP&DBP: 75.7% vs 87.3%	17.0% vs 20.0 ()
Combination Studies (n = 6)
Rajanandh et al. (2013) [26] [+Atenolol 50 mg]	India	2.5	Amlo (5)	32/32	24	Mean change; SBP: 40 vs 40; DBP: 28 vs 34; Non-significant difference	No difference: 21.9% vs 31.3%
Maksimova et al. (2013) [27] [+Atenolol]	Russia	2.5	Amlo (5)	Total: 31		LSM reduction; SBP: −15.9 vs −12.7; DBP: −7.3 vs −5.3; HR: −3 vs −4	Number: 8 vs 16
Hu and Xiao (2013) [56] [S-AM + Irbesartan vs Indapamide + Irbesartan]	China	NA	Indapamide	83	12–24	At 12 and 24 weeks; Lower 24-h DBPV, day-time SBPV with S-AM than Indapamide; At 24 weeks; Significantly lower morning SBP, 24-h DBPV and SBPV	NA
Ihm et al. (2016) [28] [Telmisartan + S-AM FDC (CKD-828): 2.5/40 and 2.5/80]	Korea	2.5	S-AM 2.5	63/63/61	8	Mean NP change in groups: 2.5/40 & 5/40 vs S-AM 2.5; SBP: −12.89, −13.79 vs −4.55; DBP: −9.67, −10.72 vs −4.93; Differences in mean change: SBP: −4.34 () and −5.61 (); DBP: −4.73 () and −5.79 (); Achieving BP <140 or <90 mmHg: 60.32% (), 60.66% () vs 28.33%	9.52% (), 14.29% () vs 27.87%
Park et al. (2016) [29] [Telmisartan + S-AM FDC: 2.5/40 and 2.5/80 mg]	Korea	2.5 & 5	T (80)	61/60/62	8	2.5/40 & 5/40 Vs T80; SBP: −10.56, −12.32 vs −2.44; DBP: −8.12, −9.58 vs −1.76; ( for both); Achieving target BP <140 or <90: 35.59%, 40.68% vs 11.86%	No differences: 18.6%, 20.0% vs 22.6%
Galappatthy et al. (2016) [16] [ACEI/ARB + BB]	Sri Lanka	2.5–5	Amlo (5–10)	76/70	16	Responders Rate: Similar- 98.57% vs 98.68%	New pitting edema: 31.40 vs 46.51% (); ARR: 15.1%; Increase in pitting edema score () & patient rated edema score () with Amlo

AC: ankle circumference, ACEI/ARB: angiotensin converting enzyme inhibitor/angiotensin receptor blocker, AEs: adverse effects, AFV: ankle-foot volume, Amlo: racemic amlodipine, ARR: absolute risk reduction, AT: atenolol, BB: beta blocker, BP: blood pressure, DBP: diastolic BP, DBPV: DBP variability, FDC: fixed-dose combination, HR: heart rate, LSM: least square mean, Nifed-SR: nifedipine sustained release, NA: not available, NR: not reported, RRR: relative risk reduction, RR: risk reduction, S-AM: S-amlodipine, SBP: systolic BP, SBPV: SBP variability, and T: telmisartan; only females; chlorthalidone 12.5 mg was added to treatments if BP remained uncontrolled with study medications.