Table 1 Baseline characteristics of studies included in the systematic review.
Study | Site | Study design | Number of participant | LRH criteria | Renin | PA excluded | Mean age, years (SD) | Male % | Ethnicity % White | Intervention and comparator | Rx Time (wks) | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean renin (SD) | Assay | Measured off BP agents | ||||||||||||
Adlin 1972 | USA | Parallel; Blinding unclear | Subgroup; 28 (Sp:18, Hct:10) | Low-normal renin groups pooled together Stimulated PRA < 400 ng/100 ml + 4 hr upright + 3-day LSD | 223 ng /100 ml | PRA -immunoassay for angiotensin II | Yes | NR | Sp:46 Hct:42 | Sp:28 Hct:30 | Sp:28 Hct:0 | Sp 50 mg QID | Hct 25 mg QID | 12 |
Carey 1972 | USA | Crossover; Double-blinded | Subgroup; 24 | Stimulated PRA < 500 ng/100 ml/3 hr x3 doses furosemide 40 mg 6hrly+ 3 hr upright | 184.8 (145.1) ng/100 ml/3 h | PRA -immunoassay for angiotensin I | Yes | Yes. 24-hr urine aldo excretion | 47.0 (9.5) | 38 | 29 | Sp 400 mg | Placebo | 6 |
Vaughan 1973 | USA | Parallel; open-labelled | Subgroup; 37 (Sp:21, Ch:16) | Below nomogram values of PRA versus 24-hr urine sodium excretion of healthy subjects whilst on LSD | 0.8 (0.4) ng/ml/hr | PRA -immunoassay for angiotensin I | Yes | NR | 54.4 (10.2) | Sp:62 Ch:38 | Sp:67 Ch:69 | Sp 50–400 mg | Ch 50–100 mg | 6 |
Douglas 1974 | USA | Crossover; Double blinded | 17 | Stimulated PRA < 1.67 ng/ml/hr x3 furosemide 40 mg 6hrly, 3 hr upright | NR range <0.2–1.4 ng/ml/hr | PRA -immunoassay for angiotensin I | Yes | Yes. 24-hr urine aldo excretion | 49.9 (8.6) | 47 | 35 | Sp 100 mg QID | Hct-Tr 25/50 mg QID | 6 |
Spark 1974 | USA | Crossover; Double blinded | 10 | Stimulated PRA < 3.5 ng /ml/hr after 4 hr upright posture and <7 ng/ml/hr after 3 hr post oral furosemide 80 mg whilst on a 120-mEq Na and 40-mEq K+ diet | NR | PRA -immunoassay for angiotensin I | Yes | Yes, method NR | 37 | NR | NR | Sp 100 mg QID | Hct 50 mg QID | 5 |
Hunyor 1975 | USA | Crossover; Double blinded | Subgroup;12 | Stimulated PRA < 50 ng%/hour on LSD 7d and 2 hr ambulation | 25.3 (10.2) ng%hr | PRA -immunoassay for angiotensin I | Yes | NR | NR for the subgroup. WG 43(range 20–59) | 75 | 50 | Sp 200–400 mg | Ch 100 mg | 4 |
Thomas 1976 | UK | Crossover, titration to effect; Double blinded | Subgroup;15 | Unstimulated lowest tertile of supine PRA on an unrestricted salt diet | NR Range 0.4–1.1 ng/ml/hr | PRA -immunoassay for angiotensin I | Yes | NR | NR | NR | 100 | Sp 200–400 mg | Ox 160–640 mg Me 750–3000 mg | 8 |
Brooks 1977 | USA | Crossover, titration to effect; Double blinded | Subgroup; 9 | Stimulated PRA < 0.8 ng/ml/hr after an overnight fast and 4 hr after oral furosemide 80 mg and an upright posture | Sp: PRA 0.2 (0.1) ng/ml/hr Hct: PRA 0.4 (0.2) ng/ml/hr | PRA – method NR | NR | NR | 45 | 21 | 11 | Sp 25–100 mg BD | Hct 25–100 mg BD or Sp/Hct 25/25–100/100 mg BD and 50/50–200/200 mg daily | 6 |
Ferguson 1977 | USA | Crossover; Double blinded | Subgroup;11 | PRA ≤ 1.0 ng/ml/hr on LSD diet and 2 hr upright posture | 0.4(0.1) ng/ml/hr | PRA -immunoassay for angiotensin I | Yes | NR | NR | NR | NR | Sp 100 mg QID | Hct 25 mg QID | 6 |
DeCarvalho 1980 | USA | Crossover, titration to effect; Double blinded | 13 | Low PRA (for sodium intake) and an expanded plasma volume, cut-off value not defined | 0.8(0.9) ng/ml/hr | PRA | Yes | NR | 49 | 23 | NR | Sp 25 mg QID titrated weekly | Tr 25 mg QID titrated weekly | 8 |
Kreeft 1983 | Canada | Crossover; Double blinded | 19 | Stimulated PRA < 3 ng/ml/hr post oral furosemide 40 mg, 4 hr upright | 1.2(0.8) ng/ml/hr | PRA -immunoassay for angiotensin I | Yes | NR | NR (Range 42–66 years) | 53 | 100 | Sp 400 mg | Ch 100 mg | 8 |
Flack 2003 | South Africa and USA | Parallel, titration to effect; Double blinded | Subgroup; NR ~ 183 | Lowest tertile of active renin (<8.2mU/L) | NR | Active renin measured by radioimmunoassay | Yes | NR | NR | NR | NR | Ep 50–200 mg | Lo 50–100 mg | 16 |
Saruta 2004 | Japan | Parallel; Double-blinded | 193 (Placebo:50, Ep50:49 Ep100:46 Ep200: 48) | Not a study inclusion criterion but baseline active plasma renin levels were consistently low | 5.7–10.1 mU/L (for each group) | Active renin concentration | Yes | NR | Ep50: 54.2 (11.3) Ep100:52.8 (10.0) Ep200:52.6 (10.8) Placebo: 54.3 (10.6) | Ep50:63 Ep100:70 Ep200:73 Placebo:68 | 0 | Ep 50–200 mg | Placebo | 8 |
Williams 2004 | USA, Canada Germany, Spain | Parallel; Double-blinded | Subgroup;149 (Ep:67, En:82) | Lowest tertile of unstimulated active renin (<7.2 pg/ml) | NR | Active renin – immunoassay | Yes | NR | NR | NR | NR | Ep 50–200 mg | En 10–40 mg | 24 |
Saha 2005 | USA | Parallel; Double-blinded | 98 (Sp:23, Am:26, SpAm:22, Placebo: 27) | Unstimulated PRA < 0.56 ng/L/sec | Sp:0.3(0.5) Am:0.2(0.6) Sp/Am:0.1(0.2) Placebo:0.2(0.3) Ng/L/sec | PRA-radioimmunoassay for angiotensin I | No (n = 20 on βblockers and n = 89 on diuretics) | No | Sp: 48.5(8.9) Am: 44.5(9.4) SpAm: 46.3(9.2) Placebo: 46.4(9.4 | Sp:48 Am:54 SpAm:59 Placebo:52 | 0 | Sp 25 mg | Am 10 mg, combination, placebo | 9 |
Weinberger 2005 | France, Spain, UK and USA | Parallel; titration-to- effect; Double blinded | 168 (Ep:86, Lo:82) | Unstimulated PRA ≤ 1.0 ng/mL/hr or active renin value ≤ 25 pg/mL ( ≤ 42.5mU/L) | Ep:11.6 mU/L Lo:12.7mU/L | Active renin concentration | Yes | Yes, method NR | Ep: 54.2 (9.7) Lo:53.9 (10.2) | Ep:47 Lo:56 | NR (% Nonblack Ep: 67 Lo:62) | Ep 100–200 mg | Lo 50–100 mg | 8 |
Hood 2007 | UK | Crossover; Double blinded | 57 | Unstimulated renin≤12 mU/L ( ≈ 0.65 ng/mL/hr), normal potassium, ARR > 750, previous response to Sp( > 20 mmHg SBP reduction) | NR Median 6.3 mU/L (range 3.4–13.0) | Renin mass | Yes | No | 59.5(11.9) | 54 | 98 | Sp 50–100 mg | Be 2.5–5 mg, Am 20–40 mg or Lo 100 mg and non-diuretic and placebo control | 5 |
