Table 3.
Characteristics of studies on lisinopril for off‐label uses
| Off‐label | Author (reference) | Comparison | Duration of study (months) | Dosing (mg day–1) | Mean age (years; if NA lisinopril group) | Final comparison group number | Final lisinopril group number | Total number |
|---|---|---|---|---|---|---|---|---|
| Proteinuric kidney disease | Juarez et al. 20 | ARB (irbesartan) | 32 | 40 or 10 | 68.7 ± 6.8 | 28 | 35 | 133 |
| Menne et al. 18 | ARB (valsartan) | 7.5 | 40 or 10 | 59.7 ± 9.5 | 42 | 47 | 133 | |
| Laverman et al. 17 | ARB (losartan) | 3 | 40 or 10 | 51 | 9 | 9 | 10 | |
| Poulsen et al. 25 | Placebo | 24 | 20 | 29.3 ± 8.6 | 10 | 11 | 22 | |
| Mogensen et al. 23 | ARB (candesartan) | 6 | 20 | 60 | 66 | 64 | 199 | |
| Tarnow et al. 27 | CCB (nisoldipine) | 48 | 20 or 10 | 35 ± 6 | 24 | 24 | 52 | |
| Crepaldi et al. 21 | CCB (nifedipine) and placebo | 36 | 2.5 or 10 or 20 | 38 ± 11 | 60 | 32 | 137 | |
| Janssen et al. 16 | CCB (amlodipine) | 4 | 5 or 10 | 47 ± 3.2 | 9 | 11 | 21 | |
| Mitchell et al. 22 | ACE inhibitor (fosinopril) | 5.5 | 20 or 40 | 67 | 14 | 13 | 94 | |
| Chaturvedi et al. 28 | Placebo | 24 | 20 or 10 | 265 | 265 | 530 | ||
| Rossing et al. 26 | CCB (nisoldipine) | 12 | 20 or 10 | 35 ± 7 | 35 | 34 | 71 | |
| Nielsen et al. 24 | β‐blocker (atenolol) | 42 | 20 or 10 | 61 ± 8 | 16 | 16 | 43 | |
| Ranieri. et al. 19 | CCB (amlodipine) | 12 | 20 | 51 ± 3 | 18 | 18 | 36 |
| Off‐label | Author (reference) | Amount of proteinuria | BP range | Type of diabetes | Diabetes | BP at baseline: mean of lisinopril group SP/DP | Underlying disease of patients with proteinuria |
|---|---|---|---|---|---|---|---|
| Proteinuric kidney disease | Juarez et al. 20 | Overt proteinuria | <180/95 | 2 | • | 153 ± 18/80 ± 11 | Diabetic nephropathic patient and stage 2 or 3 chronic kidney disease |
| Menne et al. 18 | Microalbuminuria | 85 < DP < 115 | 2 | 𝚯 | 153 ± 14.3/90.6 ± 8.3 | Essential hypertensive patient | |
| Laverman et al. 17 | Overt proteinuria | 80 < DP < 110 | ‐ | ο | 137/80 | Nondiabetic renal patients with median proteinuria | |
| Poulsen et al. 25 | Microalbuminuria | <160/90 | 1 | • | 128 ± 10.5 | Diabetic nephropathic patient | |
| Mogensen et al. 23 | Microalbuminuria | 90 < DP < 110 | 2 | • | 162.6/85.7 | Hypertensive patients with diabetic nephropathy | |
| Tarnow et al. 27 | ‐ | ‐ | 1 | • | ‐ | Hypertensive patients with diabetic nephropathy | |
| Crepaldi et al. 21 | Microalbuminuria | 115 < SP < 140, 75 < DP < 90 | 1 | • | 126 ± 8/82 ± 5 | Diabetic nephropathic patient | |
| Janssen et al. 16 | Overt proteinuria | DP < 100 with antihypertensive treatment or < 115 without medication | ‐ | ο | 163 ± 7/101 ± 3 |
Membranous glomerulopathy, chronic pyelonephritis, membranoproliferative, glomerular nephropathy, IgA nephropathy, hypertensive glomerulosclerosis, adult polycystic kidney disease, focal glomerulosclerosis, hereditary nephritis (Alport syndrome) |
|
| Mitchell et al. 22 | Microalbuminuria | 95 < DP < 110 | 2 | 𝚯 | 156 ± 3/85 ± 2 | Arteriolar nephrosclerosis or diabetic nephropathy | |
| Chaturvedi et al. 28 | Microalbuminuria | 75 < DP < 90, SP < 155 | 1 | • | 122/79 | Diabetic nephropathic patient | |
| Rossing et al. 26 | Overt proteinuria | 90 < DP < 105 | 1 | • | 155/86 | Diabetic nephropathic patient | |
| Nielsen et al. 24 | Overt proteinuria | ‐ | 2 | • | 162/85 ± 2 | Diabetic nephropathic patient | |
| Ranieri et al. 19 | Microalbuminuria | 95 < DP < 115 | ‐ | 𝚯 | 169.6 ± 15.3/104.2 ± 3.3 | Essential hypertensive patient |
| Off‐label | Author (reference) | Comparison (dose mg day–1) | Duration of study | Dose of lisinopril (mg day–1) | Mean age of total sample (years; if NA lisinopril group) | Final comparison group number | Final lisinopril group number | Total number enrolled |
|---|---|---|---|---|---|---|---|---|
| Atrial fibrillation | Van Den Berg et al. 30 | Placebo | 12 m | 5–10 | 68 ± 6 | 14 | 11 | 30 |
| Haywood et al. 31 | Chlorthalidone (12.5, 25), Amlodipine (2.5, 5, 10), doxazosin (2, 4, 8) | 6 y | 10–20‐40 | >55 | Chlorthalidone (11 695) Amlodipine (6935) doxazosin (6392) | 6702 | 39 056 | |
| CM in patients with DMD | Allen et al. 32 | Losartan (25) | 1 y | 5 | median of 12.5 y (range, 10 to 21 y) | 8 | 7 | 23 |
| Diabetic retinopathy | Mehlsen et al. 36 | Amlodipine (5) | 49 d | 10 | 27.9 ± 0.8 | 25 | 25 | 25 |
| Chaturvedi et al. 37 | Placebo | 2 y | 10–20 | 34 ± 9 | 168 | 156 | 530 | |
| Myocardial fibrosis | Brilla et al. 34 | Hydrochlorothiazide (25) | 6 m | 5–20 | 57 ± 2 | 14 | 11 | 35 |
| Kooij et al. 40 | Placebo | 8 m | 10 | 54.6 ± 12.3 | 36 | 36 | 40 | |
| Inflammatory cystoid macular oedema | Christian et al. 34 | Hydrochlorothiazide (25) | 6 m | 5–20 | 57 ± 2 | 14 | 11 | 35 |
| Left ventricular hypertrophy | Ernst et al. 33. | Chlorthalidone (12.5, 25), Amlodipine (2.5, 5, 10) | 4 y | 10–20‐40 | >55 | Chlorthalidone (12 102) Amlodipine (7151) | 7121 | 26 376 |
| Migraine | Schrader et al. 41 | Placebo | 8 m | 10 | 41 ± 9 | 47 | 47 | 60 |
| Mitral valve regurgitation | Wong et al. 35 | Placebo | 1 y | 5–10‐20 | 53.2 ± 2.4 | 11 | 12 | 23 |
| Oligospermia and infertility | Mbah et al. 42 | Placebo | 5 y | 2.5 | 30.86 ± 8.8 | 14 | 14 | 33 |
| Prevention of diabetes | ALLHAT Group 39 | Chlorthalidone (12.5, 25), Amlodipine (2.5, 5, 10) | 5 y | 10–20‐40 | >55 | Chlorthalidone (15 255) Amlodipine (9048) | 9054 | 42 418 |
| Fogari and Roberto 38 | Losartan (50) | 16 w | 20 | 55 ± 2 | 25 | 25 | 25 | |
| Prevention of pneumonia | Lee et al. 43 | Placebo | 26 w | 2.5 | 83.4 ± 6.8 | 38 | 33 | 93 |
| Off‐label | Author (reference) | Most important inclusion criteria |
|---|---|---|
| Atrial fibrillation | Van Den Berg et al. 30 | Mild to moderate stable CHF and chronic AF |
| Haywood et al. 31 | CVD risk factor | |
| CM in patients with DMD | Allen et al. 32 | Duchenne muscular dystrophy, EF <55% |
| Diabetic retinopathy | Mehlsen et al. 36 | Diabetes (type1) |
| Chaturvedi et al. 37 | Diabetes (type1) | |
| Myocardial fibrosis | Brilla et al. 34 | Symptomatic patients (dyspnoea or angina pectoris), LVH, LV diastolic dysfunction |
| Kooij et al. 40 | Inactive or chronic low‐grade activity of uveitis, inflammatory cystoid macular oedema | |
| Inflammatory cystoid macular oedema | Christian et al. 34 | Symptomatic patients (dyspnoea or angina pectoris), LVH, LV diastolic dysfunction |
| Left ventricular hypertrophy | Ernst et al. 33. | CVD risk factor |
| Migraine | Schrader et al. 41 | Migraine for more than a year |
| Mitral valve regurgitation | Wong et al. 35 | at least moderate, isolated, organic MR and an EF > 60% |
| Oligospermia and infertility | Mbah et al. 42 | being on treatment for oligospermia for at least 2 years |
| Prevention of diabetes | ALLHAT Group 39 | CVD risk factor |
| Fogari and Roberto 38 | Nondiabetic, nonobese | |
| Prevention of pneumonia | Lee et al. 43 | Tube‐fed patients |
BP, blood pressure; SP, systolic blood pressure; DP, diastolic blood pressure; NA, Not available; •, diabetic patients; ο, nondiabetic patients; 𝚯, both diabetic and nondiabetic or no data provided;
M, month; y, year; d, day; CM, cardiomyopathy; DMD, Duchenne muscular dystrophy; CVD, cardiovascular disease; CHF, congestive heart failure; AF, atrial fibrillation; EF = ejection fraction; LVH, left ventricular hypertrophy; MR, mitral regurgitation