Chart 9.3. – Drug combination studies for hypertension treatment.
| Study | Comparator regimen | Patient profile | Difference in SBP (mm Hg) | Primary outcome (% relative risk reduction) | p |
|---|---|---|---|---|---|
| Combinations of diuretics | |||||
| PREVER 179 (amiloride + chlorthalidone) | Losartan | Stage 1 hypertensive patients | -2.2 | Not assessed. Greater SBP decrease with diuretics without glucose increase | – |
| Association of ACE inhibitors and diuretics | |||||
| PROGRESS 291 (perindopril + indapamide) | Placebo | Prior stroke or TIA | -9 | -28% stroke | < 0.001 |
| ADVANCE 559 (perindopril + indapamide) | Placebo | Diabetes | -5.6 | -9% macrovascular and microvascular events | 0.04 |
| HYVET 560 (indapamide + perindopril) | Placebo | Hypertensive patients ≥ 80 years | -15 | -34% CV events | < 0.001 |
| Combination of ACE inhibitors and calcium channel blockers (amlodipine) | |||||
| ACCOMPLISH 554 (benazepril + amlodipine) | Benazepril + diuretic | High-risk hypertensive patients | -0.9 | -19.6% compound CV events | < 0.001 |
| ASCOT BPLA 558 (amlodipine + perindopril) | Beta-blocker + diuretic | Hypertensive patients with 3 or more risk factors | -2.7 | Difference not significant * | NS |
| Combination of angiotensin receptor blockers (olmesartan) and calcium channel blockers | |||||
| COLM 570 (olmesartan + CCB) | Olmesartan + diuretic | Older hypertensive Japanese patients with CV disease or risk factors | 0 | Difference not significant | NS |
| Combination of angiotensin receptor blockers and diuretics | |||||
| LIFE 526 (losartan + diuretic) | Beta-blocker + diuretic | Hypertensive patients with LVH | -1.1 | -13% CV events | 0.02 |
| Combination of calcium channel blockers and diuretics | |||||
| FEVER 571 (felodipine + diuretic) | Diuretic + placebo | Hypertensive patients | -4 | -34% CV events | < 0.001 |
| Combination of calcium channel blockers and ACE inhibitors | |||||
| SYST-EUR 572 (ACEI + ARB + diuretic) | Placebo | Older adults with ISH | -10 | -31% CV events | < 0.001 |
| SYST-CHINA 573 (ACEI + ARB + diuretic) | Placebo | Older adults with ISH | -9 | -37% CV events | < 0.004 |
| Combinations of beta-blockers and diuretics | |||||
| Coope and Warrender 574 (atenolol and diuretic) | Placebo | Older hypertensive patients | -18 | -42% stroke | < 0.003 |
| SHEP 509 (chlorthalidone and atenolol) | Placebo | Older hypertensive patients | -13 | -36% stroke | < 0.001 |
| STOP-H 561 (beta-blocker and diuretic) | Placebo | Older adults with ISH | -23 | -40% CV events | < 0.004 |
| STOP-H2 562 (ACEI and CCB) | Standard treatment (BB and diuretic) | Older hypertensive patients | 0 | No difference in CV events | – |
| Combination of two renin-angiotensin system antagonists | |||||
| ONTARGET 568 (telmisartan + ramipril) | ACEI or ARB | High-risk patients | – | Worse renal outcomes | – |
| ALTITUDE 569 (aliskiren + ARB) | ACEI or ARB | High-risk diabetic patients | – | Worse renal outcomes | – |
| Combination of fixed-dose calcium channel blocker, angiotensin receptor blocker, and diuretic | |||||
| Calhoun et al. 563 (ARB + diuretic + CCB) | ARB + diureticaor CCBb+ diuretic or ARB + CCBc | Stage 2 and 3 hypertensive patients | a: -7.6 b: -8.2 c: -6.2 | Not assessed | – |
| TRIUMPH 575 (telmisartan + amlodipine + chlorthalidone) | Usual treatment at the end of 6 months: Monotherapy in 65% and two-drug combination in 29% | Hypertensive patients | -8.8 | Not assessed | – |
Adapted from ESC, 2018. 37 ISH: isolated systolic hypertension; LVH: left ventricular hypertrophy; NS: not significant; TIA: transient ischemic attack. * significant differences in various secondary outcomes favoring ACEI + amlodipine; (a) ARB + diuretic (b) ARB + diuretic or CCB (c) diuretic or ARB + CCB.