Table 1.
Trial studies in hypertension: methodologic characteristics, results, and conclusions
| References | Study design | Comparator | Population | Duration of therapy and treatment dose (mg) | Baseline mean SBP/DBP (mmHg) | Mean reduction in SBP/DBP (mmHg) | Conclusion |
|---|---|---|---|---|---|---|---|
| Monotherapy | 8-week; | All irbesartan regimens significantly reduced mean 24-hour ambulatory DBP and SBP and were well tolerated | |||||
| Fogari et al16 | Multicenter, randomized, double-blind, placebo-controlled | Placebo | Patients aged ≥18 years with mild-to-moderate hypertension (n = 215) | Irbesartan 75 | 143.8/91.6 | 5.2/2.8 | |
| Larochelle et al18 | Randomized, double-blind | Enalapril | Patients with severe hypertension (n = 182) | Irbesartan 75 twice daily | 144.4/91.0 | 10.9/9.2 | |
| Kassler-Taub et al45 | Multicenter, randomized, double-blind, placebo-controlled | Placebo, losartan | Patients with mild-to-moderate hypertension (n = 567) | Irbesartan 150 | 143.0/91.0 | 7.3/5.7 | |
| Pool et al17 | Multicenter, randomized, double-blind, placebo-controlled | Placebo | Patients with mild-to-moderate hypertension (n = 319) | Placebo | 145.2/91.3 | 0.1/1.2 | |
| Oparil et al52 | Multicenter, randomized, double-blind, elective-titration | Losartan | Patients with mild-to-moderate hypertension (n = 432) | 12-week; | Irbesartan effectively and safely reduced SBP and DBP in patients with severe hypertension in a manner comparable to that of enalapril | ||
| Stumpe et al20 | Multicenter, randomized, double-blind | Atenolol | Patients aged ≥18 years with mild-to-moderate hypertension (n = 231) | Irbesartan 150–300 | 119.2/176.7 | 40.1/29.6 | |
| Mimran et al19 | Multicenter, randomized, double-blind | Enalapril | Patients with mild-to-moderate hypertension (n = 191) | Enalapril 20–40 | 119.0/175.4 | 39.3/30.5 | |
| Lacourciere et al49 | Multicenter, randomized, double-blind | Enalapril | Patients aged ≥65 years, with mild-to-moderate hypertension (n = 141) | 8-week; | Antihypertensive effect of 300 mg irbesartan was significantly greater than that of 100 mg losartan | ||
| Chiou et al47 | Multicenter, double-blind, randomized, parallel-group | Enalapril | Patients aged 24–75 years with mild-to-moderate hypertension (n = 54) | Irbesartan 150 | 155.3/101.1 | 12.1/9.7 | |
| Oparil et al63 | Multicenter, randomized, double-blind | Olmesartan, losartan, valsartan | Patients aged ≥18 years with essential hypertension (n = 588) | Irbesartan 300 | 155.4/100.4 | 16.4/11.7 | |
| Coca et al48 | Multicenter, randomized, double-blind | Enalapril | Patients with mild-to-moderate hypertension (n = 238) | Losartan 100 | 153.3/100.6 | 11.3/8.7 | |
| Mancia et al50 | Multicenter, randomized, double-blind, parallel-group | Valsartan | Patients aged ≥18–75 years, with mild-to-moderate hypertension (n = 426) | Placebo | 152.4/100.3 | 3.7/4.9 | |
| Hwang and Lu60 | Open-label, uncontrolled | Patients with mild-to-moderate hypertension (n = 25) | 8-week; | Irbesartan reduced BP in a dose-related manner; significant reductions over placebo were observed | |||
| Morales-Olivas et al46 | Observational, open-label, uncontrolled, longitudinal, prospective | Patients aged ≥18 years, with mild-to-moderate hypertension (n = 4,612) | Irbesartan 100–300 | 159.8/100.7 | 13.0/11.6 | ||
| Neutel et al51 | Multicenter, randomized, double-blind, parallel-group | Amlodipine | Patients with mild-to-moderate hypertension (n = 181) | Placebo | 5.0/5.5 | ||
| Coronel et al62 | Longitudinal, nonrandomized, prospective | (ACEI) Enalapril, captopril, perindopril | Patients with hypertension (nondiabetic advanced chronic kidney disease) (n = 43) | 12-week; | Reductions in trough seated DBP and seated SBP were greater with irbesartan than with losartan treatment | ||
| Irbesartan 150–300 | 155.3/100.9 | 18.0/13.8 | |||||
| Losartan 50 | 154.2/100.7 | 10.8/13.9 | |||||
| 12-week; | Both treatments significantly lowered BP from baseline; irbesartan demonstrated an excellent safety and tolerability profile | ||||||
| Irbesartan 75–150 | 158.0/101.9 | 15.0/12.3 | |||||
| Atenolol 50–100 | 158.4/101.3 | 13.2/11.6 | |||||
| 12-week; | Irbesartan was as effective as the full dose range of enalapril and demonstrated an excellent tolerability profile | ||||||
| Irbesartan 75–300 | 164/101 | 19/13 | |||||
| Enalapril 10–40 | 165/102 | 18/14 | |||||
| 8-week; | Irbesartan is an effective and well tolerated antihypertensive treatment for elderly patients with mild-to-moderate hypertension | ||||||
| Irbesartan 150–300 | 164.4/99.7 | 10.1/9.6 | |||||
| Enalapril 10–20 | 161.5/98.3 | 11.6/9.8 | |||||
| 8-week; | Irbesartan was as effective in lowering BP as enalapril; both treatments were well tolerated, while there was a significantly | ||||||
| Irbesartan 150–300 | 155/102 | 16.5/7.2 | |||||
| Enalapril 10–20 | 155/101 | 10.6/5.0 | lower incidence of cough with irbesartan compared with enalapril | ||||
| 8-week; | Irbesartan compared with olmesartan showed similar reductions in ambulatory BP and seated SBP; however it was found to be less effective at reducing diastolic BP | ||||||
| Irbesartan 150 | 156/104 | 11.0/9.9 | |||||
| Losartan 50 | 157/104 | 9.5/8.2 | |||||
| Valsartan 80 | 155/104 | 8.4/7.9 | |||||
| Olmesartan 20 | 157/104 | 11.3/11.5 | |||||
| 12-week; | Irbesartan was as effective as enalapril up to 20 mg/day; irbesartan though, was better tolerated than enalapril | ||||||
| Irbesartan 150–300 | 160.3/101.6 | 19.0/12.7 | |||||
| Enalapril 10–20 | 158.2/102.0 | 17.512.4 | |||||
| 8-week; | |||||||
| Irbesartan 150 | 159.3/100.7 | 19.0/12.7 | Irbesartan was more effective than valsartan in reducing DBP and SBP at trough and in providing greater overall 24-hour BP-lowering efficacy | ||||
| Valsartan 80 | 158/100.8 | 17.5/12.4 | |||||
| 8-week; | After treatment: | Irbesartan monotherapy once daily provided effective BP control | |||||
| Irbesartan 150–300 | 143/91 | 128/82 | |||||
| 6-month; | After treatment: | Irbesartan produced significant reductions in BP and was well tolerated | |||||
| Irbesartan 150–300 | 165.0/96.7 | 140.0/82.5 | |||||
| 4-week; | Irbesartan 150 mg demonstrated comparable efficacy to amlodipine 5 mg, thereby confirming its value as an antihypertensive treatment option | ||||||
| Irbesartan 150 | 150.7/99.7 | 12.2/9.4 | |||||
| Amlodipine 5 | 149.6/99.8 | 12.0/9.6 | |||||
| 12-months; | After treatment: | Irbesartan compared with ACEI showed similar blood pressure control | |||||
| Irbesartan 150–300 | 153.76/85.24 | 138/77 | |||||
| ACEI | 145.68/85.23 | 133/77 | |||||
| Kawano et al61 | Randomized, double-blind, placebo-controlled | Placebo | Patients with essential hypertension (n = 76) | 6-week; | Irbesartan significantly reduced 24-hour daytime and night-time BPs compared with placebo; overall safety was even greater for irbesartan than placebo | ||
| Combination therapy | Irbesartan 100 | 145.0/95.0 | 5.8/3.4 | ||||
| Rosenstock et al53 | Multicenter, randomized, double-blind, placebo-controlled | Placebo/HCTZ | Patients aged ≥28 years to 76 years, with mild-to-moderate essential hypertension (n = 238) | Placebo | 142.9/92.0 | 1.7/0.5 | |
| Kochar et al71 | Matrix | Placebo HCTZ | Patients with mild-to-moderate hypertension (n = 683) | 12-week; | Irbesartan/HCTZ produced clinically and statistically significant mean reductions over placebo in both trough seated SBP and DBP and a significant antihypertensive response | ||
| Raskin et al55 | Randomized, double-blind, placebo-controlled | Irbesartan HCTZ | Patients aged ≥18 years with mild-to-moderate essential hypertension (n = 1098) | Irbesartan/HCTZ 75–150/25 | 145.8/98.6 | 20.2/18.4 | |
| Howe et al54 | Randomized, double-blind, placebo-controlled | Placebo | Patients aged ≥21 years with mild-to-moderate essential hypertension (n = 178) | Placebo/HCTZ 25 | 147.8/99.0 | 6.0/7.4 | |
| Meaney-Mendiolea et al72 | Multicenter, nonblinded | Irbesartan | Patients (female) with mild-to-moderate hypertension (n = 188) | 8-week; | Range | The combination of HCTZ in doses up to 25 mg with irbesartan in doses up to 300 mg is safe and produces dose-dependent reductions in BP | |
| Bobrie et al58 | Randomized, prospective, open-label, blinded endpoint | Valsartan/HCTZ | Patients >18 years and <80 years with untreated or uncontrolled hypertension (n = 414) | Irbesartan 37.5, 100, and 300 | 151/100 | 7.5–14.9/7.1–10.2 | |
| Neutel et al59 | Randomized, parallel-group, open-label | Losartan/HCTZ | Patients with mild-to-moderate hypertension (n = 16) | HCTZ 6.25, 12.5, and 25 | 4.6–11.5/5.1–15.0 | ||
| Neutel et al75 | Multicenter, prospective, open-label, single-arm (INCLUSIVE) | Placebo HCTZ | Patients aged ≥18 years with hypertension and uncontrolled systolic BP (n = 736) | irbesartan/HCTZ 37.5–300/6.25–25 | 10.2–23.1/8.1–15.0 2.3/3.5 | ||
| Neutel et al73 | Multicenter, randomized, double-blind, active-controlled | Irbesartan | Patients with uncontrolled hypertension (n = 697) | Placebo | |||
| Franklin et al68 | Multicenter, randomized, double-blind, active-controlled, forced-titration | Irbesartan HCTZ | Patients with moderate and severe hypertension (n = 1235) | 12-month; | Long-term therapy with irbesartan/HCTZ is safe, well tolerated, and maintains normalized BP in >80% of patients | ||
| Cushman et al64 | Prospective, open-label, single-arm | Placebo HCTZ | Patients aged ≥18 years with hypertension (n = 844) | Irbesartan/HCTZ 75–300/12.5–25 | 151.6/100.4 | 20.6/15.6 | |
| Neutel et al76 | Randomized, double-blind, active-controlled, parallel-group | Irbesartan HCTZ | Patients with moderate hypertension (n = 538) | 8-week; | Irbesartan/HCTZ produced clinically and statistically significant mean reductions in 24-hour ABP compared with placebo | ||
| Ofili et al74 | Multicenter, prospective, open-label, single-arm (INCLUSIVE1) | Patients (women) aged ≥18 years with hypertension (n = 436) | Irbesartan/HCTZ 75/12.5 | 150.2/93.4 | 21.6/12.0 | ||
| Fogari et al67 | Prospective, randomized, open-label, blinded, end-point (PROBE) | Valsartan/amlodipine | Very elderly patients with hypertension (n = 94) | Irbesartan/HCTZ 150/12.5 | 152.6/93.5 | 22.1/13.5 | |
| Placebo | 148.3/93.2 | 6.4/3.5 | |||||
| 24-week; | Irbesartan alone or combined with HCTZ showed excellent antihypertensive efficacy with a low incidence of adverse events | ||||||
| Irbesartan/HCTZ 150–300/12.5–25 | 136.5/84.8 | 28.1/ 20.0 | |||||
| 8-week; | 153/91 | 14.8/8.2 | Irbesartan/HCTZ is more effective than valsartan/HCTZ in hypertensive patients | ||||
| Irbesartan/HCTZ 150/12.5 | 153/90 | 11.6/6.8 | |||||
| Valsartan/HCTZ 80/12.5 | |||||||
| 4-week; | Irbesartan 50 mg/HCTZ 12.5 mg resulted in greater reductions in ambulatory BP than losartan 50 mg/HCTZ 12.5 mg | ||||||
| Irbesartan/HCTZ 150/12.5 | 149.2/92.6 | 16.0/10.5 | |||||
| Losartan/HCTZ 50/12.5 | 142.7/89.0 | 11.1/6.1 | |||||
| 18-week; | Irbesartan/HCTZ treatment achieved SBP goals in more than 75% of patients uncontrolled on monotherapy | ||||||
| Irbesartan/HCTZ 150–300/12.5–25 | 154.0/91.3 | 21.5/ 10.4 | |||||
| 7-week; | In patients with severe hypertension, irbesartan/HCTZ combination therapy lowered BP more rapidly and to a greater extent than maximum-dose irbesartan monotherapy | ||||||
| Irbesartan 150–300 | 171.6/113.3 | 31.7/24.5 | |||||
| Irbesartan/HCTZ 150–300/12.5–25 | 171.5/113.4 | ||||||
| 12-week; | Irbesartan/HCTZ combination therapy was well tolerated and more effective than irbesartan or HCTZ monotherapy in lowering BP in patients with moderate-to-severe hypertension | ||||||
| Irbesartan 300 | 168.4/108.4 | 21.7/17.3 | |||||
| HCTZ 25 | 162.0/97.6 | 15.7/7.2 | |||||
| Irbesartan/HCTZ 300/25 | 167.5/106.8 | 29.9/20.4 | |||||
| 8-week; | Irbesartan/HCTZ combination therapy allowed SBP goal attainment in 73% of patients aged >65 years whose hypertension was previously uncontrolled with monotherapy | ||||||
| HCTZ 12.5 | 156.5/85.6 | 31.7/24.5 | |||||
| Irbesartan/HCTZ 150–300/12.5–25 | |||||||
| 12-week; | Irbesartan/HCTZ is well tolerated and achieves rapid and sustained reductions in SBP/DBP in patients with moderate hypertension | ||||||
| Irbesartan/HCTZ 150–300/12.5–25 | 161.7/97.5 | 28.3/15.2 | |||||
| Irbesartan 150–300 | 161.4/97.9 | 19.5/11.1 | |||||
| HCTZ 12.5–25 | 162/97.6 | 16.5/7.8 | |||||
| 8-week; | Irbesartan/HCTZ treatment was effective and well tolerated in a diverse population of women whose BP was previously uncontrolled on monotherapy | ||||||
| Irbesartan/HCTZ 300/25 | 153.9/90.3 | 22.9/10.3 | |||||
| 4-week; | In very elderly hypertensive patients, treatment with both valsartan/amlodipine combination and irbesartan/HCTZ combination was similarly effective in reducing clinical as well as ambulatory BP levels | ||||||
| Valsartan/amlodipine 160/5 | 163.2/89.8 | 22.9/15.6 | |||||
| Irbesartan/HCTZ 300/12.5 | 162.7/90.1 | 29.6/15.4 | |||||
| Chrysant et al66 | Multicenter, prospective, open-label, single-arm (INCLUSIVE trial) | Placebo HCTZ | Patients aged ≥18 years with isolated systolic hypertension (n = 443) | 16-week; | Once-daily fixed-dose irbesartan/HCTZ combination treatment provided effective and well tolerated BP-lowering | ||
| Franklin and Neutel69 | Randomized double-blind trial | No comparator | Patients with severe uncontrolled hypertension (n = 468) | HCTZ 12.5 | 156.2/88.7 | 21.4/10.1 | |
| Bobrie et al57 | Multicenter, parallel-group, prospective, randomized, open-label, blinded endpoint (I-COMBINE) | Amlodipine | Patients with essential, uncontrolled hypertension (n = 287) | Irbesartan/HCTZ 150–300/12.5–25 | |||
| Bobrie et al56 | Multicenter, parallel-group, prospective, randomized, parallel-group, open-label, blinded-end point (I-AAD) | Irbesartan | Patients with essential, uncontrolled hypertension (n = 320) | 7-week; | Range | Irbesartan/HCTZ was rapidly effective regardless of age, obesity, T2DM, and baseline SBP; treatment was well tolerated | |
| Al Balushi et al65 | Retrospective, observational | Valsartan/HCTZ | Patients with mild-to-moderate hypertension (n = 232) | Irbesartan/HCTZ 300/25 | 191.2/115.1 | 28.0–42.9/22.9–27.2 | |
| Huang et al70 | Multicenter, single-arm, prospective | No comparator | Patients with moderate-to-severe hypertension (n = 501) | 10-week; | Fixed-dose combination irbesartan/amlodipine suggests greater efficacy over monotherapy in lowering SBP | ||
| Irbesartan/amlodipine 150/5 | 148.5/84.8 | 12.4/5.6 | |||||
| Amlodipine 5 | 149.2/85.1 | 6.3/3.0 | |||||
| 10-week; | There was a greater antihypertensive efficacy of the fixed-dose combination of irbesartan 300/amlodipine 5 mg over irbesartan 300 alone in lowering systolic BP; both treatments were well tolerated | ||||||
| Irbesartan/amlodipine 300/5 | 152.7/86.6 | 18.7/8.6 | |||||
| Irbesartan 300 | 150.4/86.0 | 9.9/3.9 | |||||
| 3-month; | The irbesartan/HCTZ combination was associated with significant reductions in both SBP and DBP when compared with valsartan/HCTZ combinations; reductions were noted more in diabetics than nondiabetics | ||||||
| Irbesartan/HCTZ 150/12.5 | 153/81 | 9.0/5.0 | |||||
| Valsartan/HCTZ 80–160/12.5 | 144/77 | 2.0/0.0 | |||||
| 12-week; | The fixed irbesartan/HCTZ combination may control BP to the target level in about 60% of Chinese patients with moderate-to-severe hypertension, with an acceptable safety profile |
Abbreviations: HCTZ, hydrochlorothiazide; ACEI, angiotensin-converting enzyme inhibitor; BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure; T2DM, type 2 diabetes mellitus.