1 Introduction
2 Disparities in Hypertension
2.1 Blacks
2.2 Hispanics/Latinos
2.3 Asians
3 Implications of Adherence and Persistence to Antihypertensive Therapy
4 Benefits of Single-Pill Combination Therapy
5 Focus on Combination Amlodipine/Valsartan in Non-Whites with Hypertension
Author | Study population | Design | Treatment groups | Efficacy | Safety |
---|---|---|---|---|---|
Sub-Saharan African blacks | |||||
Odili et al. [53] |
N = 140 sub-Saharan African patients with BP 140–179/90–109 mmHg and ≤2 additional risk factors | 6-month, multicenter, randomized, open-label (blinded assessment of BP) | Amlodipine/valsartan 5/160 mg; bisoprolol/HCTZ 5/6.25 mg. Amlodipine and bisoprolol doses doubled to achieve BP <140/90 mmHg, along with the possible addition of α-methyldopa | Mean BP reductions from baseline in the combined treatment groups were 18.2/10.1 mmHg at week 2, 19.4/11.2 mmHg at week 4, 22.4/12.2 mmHg at week 8, and 25.8/15.2 mmHg at week 12. BP <140/90 mmHg: >65 % by week 2 in the combined treatment groups | Discontinuations due to AEs: 1 patient (1.4 %) in each group. Study medication adjusted in 3 patients because of heartburn, tiredness, and diarrhea (treatment group not specified) |
Black populations in the USA | |||||
Flack et al. [54] |
N = 572 black patients with MSSBP 160–199 mmHg | 12-week, multicenter, randomized, double-blind | Amlodipine/valsartan 5/160 mg × 2 weeks uptitrated to 10/160 mg × 2 weeks with optional titration at week 4 to 10/320 mg if MSSBP ≥130 mmHg; amlodipine 5 mg × 2 weeks uptitrated to 10 mg × 10 weeks. In both arms, HCTZ 12.5 mg could be added at 8 weeks if MSSBP ≥130 mmHg | LSM MSSBP/MSDBP reductions from baseline to week 8: 33.3/13.6 mmHg with amlodipine/valsartan vs. 26.6/10.8 mmHg with amlodipine (P < 0.0001/P < 0.001). MSSBP/MSDBP <140/90 mmHg at week 8: 49.8 vs. 30.2 % (P < 0.0001) | Any AE during study: 44.4 % with amlodipine/valsartan vs. 45.3 % with amlodipine. Most common AEs were peripheral edema (12.6 vs. 9.5 %), headache (4.2 vs. 5.3 %), and dizziness (2.4 vs. 2.5 %). Discontinuations due to AEs: 2.4 vs. 3.2 % |
Smith et al. [55] | Subgroup analysis of 2 studies of 3,161 patients with MSDBP 95–109 mmHg, including 2,508 white and 201 black | 8-week, multicenter, randomized, double-blind, placebo-controlled | Placebo; amlodipine 2.5 mg, 5 mg, or 10 mg; valsartan 40 mg, 80 mg, 160 mg, or 320 mg; amlodipine/valsartan 2.5/40 mg, 2.5/80 mg, 2.5/160 mg, 2.5/320 mg, 5/40 mg, 5/80 mg, 5/160 mg, 5/320 mg, 10/160 mg, or 10/320 mg. Note: results for two highest combination dose groups not reported in blacks because of limited sample size | LSM MSSBP/MSDBP reductions from baseline to week 8: white: 15.7/10.7 mmHg with amlodipine/valsartan 2.5/40 mg to 23.0/15.5 mmHg with amlodipine/valsartan 5/320 mg; black: 16.5/7.7 mmHg with amlodipine/valsartan 2.5/40 mg to 17.5/17.9 mmHg with amlodipine/valsartan 5/320 mg. In both white and black patients, greater BP reductions were observed in each of the combination therapy groups compared with the respective monotherapies or placebo | Any AE during study: white: 41.5 % with any amlodipine/valsartan combination, 43.6 % with amlodipine, 37.3 % with valsartan, and 34.0 % with placebo; black: 54.1 % with any amlodipine/valsartan combination, 51.7 % with amlodipine, 47.5 % with valsartan, and 61.5 % with placebo. Most common AEs with any amlodipine/valsartan combination: white: peripheral edema (5.0 vs. 2.6 % placebo), nasopharyngitis (4.0 vs. 1.9 %), headache (3.6 vs. 6.0 %), and upper respiratory tract infection (2.3 vs. 1.1 %); black: nasopharyngitis (9.2 vs. 7.7 %), upper respiratory tract infection (7.1 vs. 7.7 %), headache (6.1 vs. 7.7 %), and peripheral edema (5.1 vs. 15.4 %) |
Ofili et al. [42] | Post hoc analysis of 728 patients who were treatment naïve or not responding to ARB monotherapy (other than valsartan) for ≥4 weeks (MSSBP 150–199 mmHg), including 474 white, 198 African American, and 165 Hispanic | 12-week, multicenter, randomized, double-blind | Moderate treatment: amlodipine/valsartan 5/160 mg × 4 weeks uptitrated to amlodipine/valsartan/HCTZ 5/160/12.5 mg × 8 weeks; intensive treatment: amlodipine/valsartan 5/320 mg × 2 weeks uptitrated to amlodipine/valsartan 10/320 mg × 2 weeks uptitrated to amlodipine/valsartan/HCTZ 10/320/12.5 mg × 8 weeks. In both arms, another 12.5 mg of HCTZ could be added at 8 weeks if MSSBP >140 mmHg | LSM MSSBP reductions from baseline to week 4: white: 19.0 mmHg with moderate treatment vs. 23.5 mmHg with intensive treatment (P < 0.001); African American: 18.1 vs. 20.4 mmHg (P = NS); Hispanic: 17.5 vs. 23.4 mmHg. MSSBP/MSDBP <140/90 mmHg at week 4: white: 30.5 vs. 44.7 % (P < 0.01); African American: 26.9 vs. 37.1 % (P < 0.05); Hispanic: 33.3 vs. 54.8 % (P < 0.01) | Any AE during study: white: 38.3 % with moderate treatment vs. 37.7 % with intensive treatment; African American: 35.1 vs. 36.2 %; Hispanic: 23.5 vs. 22.4 %. Most common AEs were peripheral edema (white: 5.8 vs. 11.0 %; African American: 2.1 vs. 3.8 %; Hispanic: 2.5 vs. 8.2 %), dizziness (white: 4.6 vs. 4.2 %; African American: 2.1 vs. 6.7 %; Hispanic: 2.5 vs. 2.4 %), and headache (white: 2.1 vs. 2.9 %; African American: 3.8 vs. 3.2 %; Hispanic: 2.4 vs. 4.9 %) |
Hispanics/Latinos | |||||
Destro et al. [59] |
N = 646 patients with MSSBP 160–199 mmHg, including 224 Hispanic/Latino and 33 black | 8-week, multicenter, randomized, double-blind | Amlodipine/valsartan 5/160 mg × 2 weeks uptitrated to 10/160 mg × 6 weeks; amlodipine 5 mg × 2 weeks uptitrated to 10 mg × 6 weeks. In both arms, HCTZ could be added at 4 weeks if MSSBP ≥130 mmHg | LSM MSSBP reductions from baseline to week 4: overall: 30.1 mmHg with amlodipine/valsartan vs. 23.5 mmHg with amlodipine (P < 0.0001); Hispanic/Latino: 29.1 vs. 23.0 mmHg (P < 0.05); black: 30.4 vs. 25.1 mmHg (P = NS). MSSBP <140 mmHg at week 4: overall: 51.8 vs. 27.7 %; Hispanic/Latino: 55.1 vs. 35.8 %; black: 50.0 vs. 45.5 % | Any AE during study (results not provided by race/ethnicity): 35.2 % with amlodipine/valsartan vs. 37.2 % with amlodipine. Most common AEs were peripheral edema (12.8 vs. 17.6 %) and headache (3.7 vs. 3.1 %). Discontinuations due to AEs: 5.9 vs. 5.9 % |
Ofili et al. [42] | See results for Hispanic population under “Black populations in the USA” | ||||
Asians | |||||
Chazova et al. [56] |
N = 2,729 patients with BP >140/90 mmHg, including 1,478 Asian | 12-week, multicenter, open-label, observational, non-interventional, surveillance | Amlodipine/valsartan 5/80 mg, 10/80 mg, 5/160 mg, or 10/160 mg | Mean BP reductions from baseline to week 12: 29.2/15.1 mmHg with 5/80 mg, 36.0/16.7 mmHg with 10/80 mg, 39.9/19.4 mmHg with 5/160 mg, and 43.6/22.4 mmHg with 10/160 mg. BP <140/90 mmHg during study: 75.6 % | Any AE during study: 8.8 % across groups. Most common AEs were edema (2.3 %) and dizziness (1.4 %) |
Ke et al. [57] |
N = 698 Asian patients not responding to amlodipine 5-mg monotherapy × 4 weeks (MSDBP 90–109 mmHg), including 601 Chinese | 8-week, multicenter, randomized, double-blind | Amlodipine/valsartan 5/80 mg; amlodipine 5 mg | LSM MSSBP/MSDBP reductions from baseline to week 8: 11.4/9.7 mmHg with amlodipine/valsartan vs. 7.4/7.1 mmHg with amlodipine (P < 0.0001). MSSBP/MSDBP <140/90 mmHg at week 8: 69.2 vs. 57.6 % (P = 0.0013) | Any AE during study: 25.2 % with amlodipine/valsartan vs. 24.6 % with amlodipine. Most common AEs were hyperlipidemia (4.3 vs. 3.2 %) and dizziness (2.9 vs. 2.0 %). Discontinuations due to AEs: 2.9 vs. 2.0 % |
Huang et al. [58] |
N = 918 Asian patients not responding to valsartan 80-mg monotherapy × 4 weeks (MSDBP 90–109 mmHg), including 813 Chinese | 8-week, multicenter, randomized, double-blind | Amlodipine/valsartan 5/80 mg; valsartan 80 mg; valsartan 160 mg | LSM MSSBP/MSDBP reductions from baseline to week 8: 12.5/10.8 mmHg with amlodipine/valsartan vs. 6.0/6.3 mmHg with valsartan 80 mg and 7.7/7.2 mmHg with valsartan 160 mg (both P < 0.0001). MSSBP/MSDBP <140/90 mmHg at week 8: 70.5 vs. 44.1 % and 58.6 % (both P < 0.01) | Any AE during study: 22.1 % with amlodipine/valsartan vs. 18.2 % with valsartan 80 mg and 20.8 % with valsartan 160 mg. Most common AEs were hyperlipidemia (2.9 vs. 4.2 % and 5.0 %), dizziness (1.6 vs. 1.0 % and 2.0 %), and hyperuricemia (1.9 vs. 2.0 % and 0.3 %). Discontinuations due to AEs: 1.9 vs. 0 % and 1.7 % |