Table.
Recent Triple‐Combination Therapy Studies With ARBs
| study | study design | treatment | response rate | SBP/DBP, mm Hg |
|---|---|---|---|---|
| Calhoun et al 28 | Multinational, randomized, double‐blind, parallel‐group Forced‐titration Patients had SBP ≥145 and DBP ≥100 mm Hg | Patients with BP <140/90 mm Hg, % | Change from baseline in mean sitting BP | |
| V/H 320/25 mg | 58.3 | −32.0/−19.7 (+7.6/+5.1 vs A/V/H; P<.0001) | ||
| V/A/320/10 mg | 54.1 | −33.5/−21.5 (+6.2/+3.3 vs A/V/H; P<.0001) | ||
| A/H 10/25 mg | 44.8 | −31.5/−19.5 (+8.2/+5.3 vs A/V/H; P<.0001) | ||
| V/A/H 320/10/25 mg | 70.8 | −39.7/−24.7 | ||
| Val‐DICTATE 29 | Multicenter, randomized, active‐controlled, parallel‐group Four‐week double‐blind phase (H 25 mg or V/H 160/12.5 mg), followed by 16‐week open‐label stepped‐care starting with V/H 160/25 mg (if BP ≥140/90 mm Hg): Uptitration of V → Addition of A → Uptitration of A Patients had SBP >150 and <180 mm Hg and DBP >95 and <110 mm Hg | Estimated cumulative % (actual step % [No./No.]) with BP <140/90 mm Hg | ||
| H 25 mg | 16 (16 [23/145]) | |||
| V/H 160/12.5 mg | 37 (37 [53/145]) | |||
| V/H 160/25 mg | 64 (64 [125/195]) | |||
| V/H 320/25 mg | 78 (64 [75/118]) | |||
| V/A/H 320/5/25 mg | 84 (57 [42/74]) | |||
| V/A/H 320/10/25 mg | 89 (42 [16/38]) | |||
| EX‐STAND 30 | Randomized, double‐blind, parallel‐group, active‐controlled, multicenter Forced‐titration in combination arm, with add‐on H at week 8 (either arm) if SBP ≥130 mm Hg Patients were black with SBP ≥160 and <200 mm Hg | Patients with BP <140/90 mm Hg, % | Change from baseline (∼ SBP) | |
| Week 8 | ||||
| A 10 mg | 30.2 | −27/−11.2 | ||
| V/A 320/10 mg | 49.8; P<.0001 | −34/−14.0; P<.001 | ||
| Week 12 (opt. H) | ||||
| A/H 10/12.5 mg | 35.9 | −30/−12.8 | ||
| V/A/H 320/10/12.5 mg | 57.2; P<.0001 | −37/−16.2; P<.001 | ||
| EX‐EFFeCTS 31 | Multinational, randomized, double‐blind, parallel‐group Forced‐titration, with add‐on H at week 4 if SBP ≥130 mm Hg Patients had SBP ≥160 and <200 mm Hg | Patients with BP <140/90 mm Hg, % | Change from baseline and incremental reduction with optional H | |
| Week 4 | ||||
| A 10 mg | 23.8 | −23.5/−8.6 (change from baseline) | ||
| V/A 160/10 mg | 45.3 | −30.1/−12.5 (change from baseline) | ||
| Week 8 | ||||
| A/H 10/12.5 mg | 31.1 | −3.1/NR (incremental reduction) | ||
| V/A/H 160/10/12/5 mg | 53.0 | −6.9/NR (incremental reduction) | ||
| EX‐FAST 32 | Multinational, randomized, double‐blind, parallel‐group Fixed‐dose, with add‐on H at week 8 and uptitration at week 12 if BP ≥140/90 mm Hg or ≥130/80 mm Hg (latter if diabetes) Patients had SBP <180 and DBP <110 mm Hg (<160 and <100 mm Hg in diabetes) on monotherapy | Patients with BP <140/90 mm Hg (non‐DM) or BP <130/80 mm Hg (DM), % | ||
| Week 8 | ||||
| V/A 160/5 mg | 71.1 | −16.5/−9.3 | ||
| V/A 160/10 mg | 76.4 | −19.2/−11.3; P<.001 | ||
| Week 16 | ||||
| V/A/H 160/5/12.5–25 mg | 72.7 | −17.5/−10.4 | ||
| V/A/H 160/10/12.5–25 mg | 74.8 | −20.0/−11.6; P<.001 | ||
| Volpe et al 33 | Multicenter, open‐label Stepped‐care: Uptitration of A → Addition of H → Uptitration of H Eligibility by pretreatment: Newly diagnosed or A‐naïve with SBP, DBP, and 24‐hour DBP ≥160, ≥100, and ≥84 mm Hg (30% of daytime values >90 mm Hg) A‐pretreated with SBP, DBP, and 24‐hour DBP ≥140, ≥90, and ≥80 mm Hg (with 30% of daytime values >85 mm Hg) | Cumulative % (step % [No./No.]) with BP <140/90 mm Hg (non‐DM) BP <130/80 mm Hg (DM) | Incremental change in BP (end point BP) | |
| O/A 40/5 mg | 48.6 (74.3 [336/452]) | NA (131.4/83.1) | ||
| O/A 40/10 mg | 60.8 [59.0 [85/144]) | −8.8/−5.5 (135.0/85.4) | ||
| O/A/H 40/10/12.5 mg | 65.5 (47.1 [32/68]) | −10.2/−6.3 (138.3/87.3) | ||
| O/A/H 40 10/25 mg | 66.9 (33.3 [9/27]) | −3.8/−3.7 (145.6/89.7) | ||
| Gomes et al 34 | Multicenter, open‐label Stepped‐care: Addition of H → Uptitration of O and H → Addition of A Patients had SBP ≥140 and <180 mm Hg and DBP ≥90 and <110 mm Hg | Cumulative % (step % [No./No.]) with BP <130/85 mm Hg | Change from baseline in patients achieving a BP <130/85 mm Hg | |
| O 20 mg | 26 (26 [37/144]) | −30.5/−19.1 | ||
| O/H 20/12.5 mg | 49 (31 [33/106]) | −34.8/−21.6 | ||
| O/H 40/25 mg | 74 (49 [36/73]) | −34.2/−19.8 | ||
| O/A/H 40/5/25 mg | 86 (59 [19/32]) | −44.4/−20.0 | ||
| Neutel et al 35 | Multicenter, open‐label Stepped‐care: Uptitration of O → Addition of H → Uptitration of H → Addition of A → Uptitration of A Patients had DBP 90–109 mm Hg and SBP <200 mm Hg | Cumulative % with BP <140/90 mm Hg (BP <130/85 mm Hg) | Change from baseline | |
| O 20 or 40 mg | 58.7 (35.2) | −17.7/−10.7 | ||
| O/H 40/12.5 or 40/25 mg | 83.2 (69.3) | −29.3/−16.1 | ||
| O/A/H 40/25/5 or 40/25/10 mg | 93.3 (87.7) | −33.7/−18.2 | ||
| Neutel et al 36 | Multicenter, open‐label subgroup of study above | Stage 1 HTN: Cumulative % with BP <140/90 mm Hg (BP <130/85 mm Hg) | Stage 1 HTN: Change from baseline | |
| O 20 or 40 mg | 79.7 (55.7) | −16.7/−11.6 | ||
| O/H 40/12.5 or 40/25 mg | 93.7 (88.6) | −24.8/−15.8 | ||
| O/A/H 40/25/5 or 40/25/10 mg | 97.5 (96.2) | −26.4/−16.5 | ||
| Stage 2 HTN: Cumulative % with BP <140/90 mm Hg (BP <130/85 mm Hg) | Stage 2 HTN: Change from baseline | |||
| O 20 or 40 mg | 42.0 (19.0) | −18.4/−10.0 | ||
| O/H 40/12.5 or 40/25 mg | 75.0 (54.0) | −32.7/−16.3 | ||
| O/A/H 40/25/5 or 40/25/10 mg | 90.0 (81.0) | −39.1/−19.4 | ||
Abbreviations: A, amlodipine; ARBs, angiotensin receptor blockers; BP, blood pressure; DBP, diastolic blood pressure; DM, diabetes mellitus; EX‐EFFeCTS, the Exforge Efficacy and Control in Treatment of Stage 2 Hypertension trial; EX‐FAST, the Exforge in Failure After Single Therapy trial; EX‐STAND, Exforge Evaluation in Stage 2 Hypertensives of African Descent trial; H, hydrochlorothiazide; HTN, hypertension; NA, not applicable; NR, not reported; O, olmesartan; SBP, systolic blood pressure; V, valsartan; Val‐DICTATE, the Valsartan Hydrochlorothiazide Diuretic for Initial Control and Titration to Achieve Optimal Therapeutic Effect trial.