Background
Rationale
Objectives
Methods
Protocol
Eligibility criteria
Information sources and search
Study selection
Data collection process
Data items
Risk of bias in individual studies
Summary measures
Synthesis of results
Quality-assessment of the evidence
High = We are very confident that the true effect lies close to that of the estimate of the effect. |
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Moderate = We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. |
Low = Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. |
Very low = We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect. |
Results
Study selection
Study characteristics
Study, year (reference) | Comparisons (initial drug-dosages) | Sample size (total, included in analysis) | Age group (years) | Follow-up (mean, years) |
---|---|---|---|---|
VA II 1970 [43] | Hydrochlorothiazide (50 mg/day) + reserpine (0.1 mg/day) + hydralazine hydrochloride (25 mg/day) vs. placebo | 380 | 30 to 73 | 3.3 |
Oslo hypertension study 1980 [27] | Hydrochlorothiazide (50 mg/day) vs. no treatment | 785 | 40 to 49 | 5.5 |
EWPHE 1985 [44] | Hydrochlorothiazide (25 mg/day) + triamteren (50 mg/day) vs. placebo | 840 | > 60 | 4.7 |
Coope 1986 [45] | Atenolol (100 mg/day) or bendrofluazide (5 mg/day) vs. no treatment | 884 | 60 to 79 | 4.4 |
HAPPHY 1987 [28] | Bendroflumethiazide (5 mg/day) or hydrochlorothiazide (50 mg/day) vs. atenolol (100 mg/day) or metoprolol 200 mg/day) | 6,569 | 40 to 64 | 3.8 |
STOP 1 1991 [46] | Atenolol (50 mg/day) or HCTZ (25 mg/day) (add-on drugs: amiloride (2.5 mg/day) or metoprolol (100 mg/day) or pindolol (5 mg/day)) vs. placebo | 1,627 | 70 to 84 | 2 |
SHEP 1991 [26] | Chlortalidone (12.5 mg/day) vs. placebo | 4,736 | > 60 | 4.5 |
MRC 2 1992 [29] | Hydrochlorothiazide+amiloride (25 + 2.5 mg/day) vs. atenolol (50 mg/day) vs. placebo | 4,396 | 65 to 74 | 5.8 |
SYST-EUR 1997 [47] | Nitrendipine (10 mg/day) vs. placebo | 4,695 | > 60 | 4 |
Sun 1997 [25] | Nitrendipine (10 mg/day) (starting dose: 10 mg × 3, reduced to 10 mg × 1) vs. usual care | 2,080 | > 15 | 4.7 |
CAPPP 1999 [30] | Captopril (50 mg/day) vs. atenolol (50 to 100 mg/day) or metoprolol (50 to 100 mg/day) or hydrochlorothiazide (25 mg/day) or bendroflumethiazide (2.5 mg/day) | 10,985 | 25 to 66 | 6.1 |
NICS-EH 1999 [31] | Nicardipine (20 mg × 2/day) vs. Trichlormethiazide (2 mg/day) | 414 | ≥ 60 | 4.6 (nicardipine group) and 3.9 (trichlormethia-zide group) |
STOP-2 1999 [32] | Atenolol (50 mg/day) or metoprolol (100 mg/day) or pindolol (5 mg/day) or hydrochlorothiazide (25 mg/day)+amilorid (2.5 mg/day) vs. enalapril (10 mg/day) or lisinopril (10 mg/day) vs. felodipine (2.5 mg/day) or isradipine (2.5 mg/day) | 6,614 | 70 to 84 | 4 to 6 |
Doxazosine (2 mg/day) vs. chlorthalidone (12.5 mg/day) vs. amlodipine (2.5 mg/day) vs. lisinopril (10 mg/day) | 42,424 | > 55 | 4.9 for chlorthalidone vs. amlodipine vs. lisinopril. 3.3 (median) for chlorthalidone vs. doxazosine | |
NORDIL 2000 [34] | Diltiazem (180 to 360 mg/day) vs. thiazide (not specified) or beta-blocker (not specified) | 10,881 | 50 to 74 | 4.5 |
INSIGHT 2000 [35] | Nifedipine (30 mg/day) vs. hydrochlorothiazide (25 mg/day)+amilorid (2.5 mg/day) | 6,321 | 55 to 80 | ~3.5 |
LIFE 2002 [36] | Losartan (50 mg/day) vs. atenolol (50 mg/day) | 9,193 | 55 to 80 | 4.8 |
ANBP 2 2003 [37] | ACE-inhibitor (unspecified type and dosage) vs. thiazide-diuretic (unspecified type and dosage) | 6,083 | 65 to 84 | 4.1 |
CONVINCE 2003 [38] | Verapamil (180 mg/day) vs. atenolol (50 mg/day) or hydrochlorothiazide (12.5 mg/day) | 16,602 | > 55 | 3 |
HYVET-PILOT 2003 [39] | Lisinopril (2.5 mg/day) vs. bendroflumethiazide (2.5 mg/day) vs. no treatment | 857 | > 80 | 1.1 |
SHELL 2003 [40] | Chlorthalidone (12.5 mg/day) vs. lacidipine (4 mg/day) | 1,882 | > 60 | 2.7 (median) |
VALUE 2004 [49] | Valsartan (80 mg/day) vs. amlodipine (5 mg/day) | 15,245 | > 50 | 4.2 |
E-COST 2005 [41] | Candesartan (4 or 8 mg/day) vs. "conventional based regimen" | 1,630 | 35 to 79 | 3.1 |
CASE-J 2008 [42] | Candesartan (8 mg/day) vs. amlodipine (5 mg/day) | 4,703 | 63.8 (mean) | 3.2 |
HYVET 2008 [48] | Indapamid (1.5 mg/day) vs. placebo | 3,845 | ≥ 80 | 2.1 |
Synthesis of results
Relative risk estimates and quality of evidence
All-cause mortality | Myocardial infarction | Stroke | |
---|---|---|---|
Diuretics vs.BB | 0.90 (0.80 to 1.01) | 0.82 (0.68 to 0.98) | 0.83 (0.68 to 1.07) |
⊕ ⊕ ⊕ O | ⊕ ⊕ OO | ⊕ ⊕ OO | |
Diuretics vs. ACE | 1.00 (0.93 to 1.08) | 1.00 (0.88 to 1.15) | 0.94 (0.81 to 1.10) |
⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ O | |
Diuretics vs. CCB | 1.03 (0.96 to 1.10) | 0.96 (0.84 to 1.07) | 1.12 (0.97 to 1.29) |
⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ O | ⊕ ⊕ OO | |
Diuretics vs.alpha-blockers | 0.98 (0.87 to 1.12) | 0.99 (0.80 to 1.23) | 0.85 (0.66 to 1.12) |
⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ O | ⊕ ⊕ OO | |
Diuretics vs.ARB | 1.02 (0.92 to 1.14) | 0.83 (0.69 to 1.03) | 1.02 (0.82 to 1.28) |
⊕ ⊕ OO | ⊕ OOO | ⊕ OOO | |
BB vs. ACE | 1.12 (0.98 to 1.27) | 1.22 (1.00 to 1.52) | 1.13 (0.86 to 1.42) |
⊕ OOO | ⊕ ⊕ OO | ⊕ OOO | |
BB vs. CCB | 1.14 (1.01 to 1.28) | 1.17 (0.97 to 1.42) | 1.34 (1.05 to 1.64) |
⊕ ⊕ OO | ⊕ OOO | ⊕ ⊕ OO | |
BB vs. alpha-blockers | 1.09 (0.93 to 1.30) | 1.20 (0.92 to 1.61) | 1.02 (0.71 to 1.42) |
⊕ OOO | ⊕ OOO | ⊕ OOO | |
BB vs. ARB | 1.14 (1.02 to 1.28) | 1.02 (0.84 to 1.27) | 1.23 (0.96 to 1.49) |
⊕ ⊕ ⊕ ⊕ | ⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ O | |
ACE vs. CCB | 1.02 (0.95 to 1.10) | 0.96 (0.83 to 1.07) | 1.19 (1.03 to 1.38) |
⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ O | |
ACE vs. alpha-blockers | 0.98 (0.85 to 1.14) | 0.99 (0.77 to 1.27) | 0.91 (0.67 to 1.24) |
⊕ ⊕ OO | ⊕ OOO | ⊕ OOO | |
ACE vs. ARB | 1.02 (0.91 to 1.14) | 0.84 (0.68 to 1.04) | 1.08 (0.86 to 1.37) |
⊕ ⊕ OO | ⊕ OOO | ⊕ OOO | |
CCB vs. alpha-blockers | 0.96 (0.83 to 1.11) | 1.03 (0.82 to 1.34) | 0.77 (0.57 to 1.04) |
⊕ ⊕ OO | ⊕ OOO | ⊕ OOO | |
CCB vs. ARB | 1.00 (0.91 to 1.10) | 0.87 (0.74 to 1.06) | 0.91 (0.75 to 1.11) |
⊕ ⊕ ⊕ ⊕ | ⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ O | |
Alpha-blockers vs. ARB | 1.04 (0.88 to 1.23) | 0.84 (0.63 to 1.14) | 1.20 (0.85 to 1.69) |
⊕ ⊕ OO | ⊕ OOO | ⊕ OOO |
Angina | Heart failure | Diabetes incidence | |
---|---|---|---|
Diuretics vs. BB | 0.96 (0.28 to 5.78) | 0.73 (0.54 to 0.96) | 1.09 (0.80 to 1.44) |
⊕ OOO | ⊕ ⊕ ⊕ O | ⊕ ⊕ OO | |
Diuretics vs. ACE | 0.97 (0.42 to 2.51) | 0.88 (0.76 to 1.06) | 1.43 (1.12 to 1.83) |
⊕ ⊕ OO | ⊕ ⊕ OO | ⊕ ⊕ ⊕ O | |
Diuretics vs. CCB | 1.05 (0.56 to 2.19) | 0.73 (0.62 to 0.84) | 1.27 (1.05 to 1.57) |
⊕ ⊕ OO | ⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ ⊕ | |
Diuretics vs. alpha-blockers | 0.89 (0.31 to 2.52) | 0.51 (0.40 to 0.64) | - |
⊕ OOO | ⊕ ⊕ ⊕ O | ||
Diuretics vs. ARB | 0.86 (0.39 to 3.27) | 0.80 (0.61 to 0.98) | 1.59 (1.23 to 2.12) |
⊕ OOO | ⊕ ⊕ OO | ⊕ ⊕ OO | |
BB vs. ACE | 1.03 (0.17 to 3.76) | 1.21 (0.91 to 1.69) | 1.31 (0.95 to 1.88) |
⊕ OOO | ⊕ OOO | ⊕ OOO | |
BB vs. CCB | 1.10 (0.23 to 3.31) | 1.00 (0.76 to 1.33) | 1.17 (0.89 to 1.61) |
⊕ OOO | ⊕ OOO | ⊕ OOO | |
BB vs. alpha-blockers | 0.93 (0.11 to 4.35) | 0.69 (0.50 to 1.02) | - |
⊕ OOO | ⊕ OOO | ||
BB vs. ARB | 0.88 (0.31 to 2.58) | 1.08 (0.86 to 1.38) | 1.46 (1.15 to 1.98) |
⊕ ⊕ OO | ⊕ ⊕ ⊕ ⊕ | ⊕ ⊕ ⊕ ⊕ | |
ACE vs. CCB | 1.08 (0.48 to 2.44) | 0.82 (0.69 to 0.94) | 0.89 (0.73 to 1.10) |
⊕ OOO | ⊕ ⊕ ⊕ O | ⊕ ⊕ OO | |
ACE vs. alpha-blockers | 0.91 (0.22 to 3.42) | 0.58 (0.43 to 0.75) | - |
⊕ OOO | ⊕ ⊕ OO | ||
ACE vs. ARB | 0.86 (0.35 to 3.50) | 0.90 (0.67 to 1.10) | 1.11 (0.85 to 1.51) |
⊕ OOO | ⊕ OOO | ⊕ OOO | |
CCB vs. alpha-blockers | 0.85 (0.23 to 2.78) | 0.70 (0.53 to 0.92) | - |
⊕ OOO | ⊕ ⊕ OO | ||
CCB vs. ARB | 0.81 (0.45 to 2.30) | 1.10 (0.87 to 1.31) | 1.25 (1.02 to 1.56) |
⊕ ⊕ OO | ⊕ ⊕ ⊕ O | ⊕ ⊕ ⊕ ⊕ | |
Alpha-blockers vs. ARB | 0.95 (0.29 to 5.71) | 1.57 (1.09 to 2.12) | - |
⊕ OOO | ⊕ ⊕ OO |
Ranking of drug-classes
Mortality | Myocardial infarction | Stroke | Angina | Heart failure | Diabetes | |
---|---|---|---|---|---|---|
Diuretics | 18% | 79% | 46% | 33% | 99% | 1% |
BB | 1% | 2% | 3% | 38% | 10% | 9% |
ACE | 23% | 75% | 11% | 27% | 83% | 96% |
CCB | 54% | 36% | 98% | 51% | 1% | 62% |
Alpha-blocker | 25% | 58% | 9% | 45% | 0% | - |
ARB | 49% | 5% | 60% | 22% | 22% | 99% |
Diuretics and/or BB | 84% | 45% | 71% | 22% | 65% | 33% |
"Conventional" | 46% | 0% | 1% | - | 20% | - |
Consistency of network-model
Outcome | MTM-estimate (95% Crl) | Direct estimate (95% Crl) | Indirect estimate (95% Crl) |
P-value for inconsistency | |
---|---|---|---|---|---|
Diuretics vs. beta-blockers | Diabetes- incidence | 1.09 | 0.88 | 1.31 | 0.13 |
(0.80 to 1.44) | (0.59 to 1.32) | (0.88 to 2.17) | |||
Diuretics vs. ACE-inhibitors | Diabetes- incidence | 1.43 | 1.54 | 1.25 | 0.24 |
(1.12 to 1.83) | (1.14 to 2.10) | (0.89 to 1.79) | |||
Diuretics vs. placebo | All-cause mortality | 0.88 | 0.89 | 0.80 | 0.29 |
(0.80 to 0.95) | (0.82 to 0.97) | (0.68 to 0.96) | |||
Beta-blockers vs. ARB | Stroke | 1.23 | 1.34 | 1.00 | 0.17 |
(0.96 to 1.49) | (1.03 to 1.74) | (0.69 to 1.41) | |||
Beta-blockers vs. ARB | Diabetes- incidence | 1.46 | 1.32 | 1.98 | 0.13 |
(1.15 to 1.98) | (0.97 to 1.82) | (1.26 to 3.40) | |||
ACE- inhibitors vs. CCB | All-cause mortality | 1.02 | 1.05 | 0.95 | 0.21 |
(0.95 to 1.10) | (0.96 to 1.13) | (0.82 to 1.09) | |||
ACE- inhibitors vs. CCB | Heart fail ure | 0.82 | 0.79 | 0.68 | 0.29 |
(0.69 to 0.94) | (0.67 to 0.95) | (0.52 to 0.90) | |||
ACE-inhibitors vs. placebo | All-cause mortality | 0.87 | 1.30 | 0.86 | 0.08 |
(0.79 to 0.96) | (0.82 to 2.14) | (0.77 to 0.95) | |||
Diuretics and/or beta-blockers vs. placebo | All-cause mortality | 0.82 | 0.57 | 0.85 | 0.06 |
(0.73 to 0.92) | (0.34 to 0.84) | (0.75 to 0.96) | |||
CCB vs. ARB | Stroke | 0.91 | 0.86 | 1.15 | 0.19 |
(0.75 to 1.11) | (0.69 to 1.05) | (0.78 to 1.70) | |||
CCB vs. ARB | Diabetes- incidence | 1.25 | 1.29 | 0.86 | 0.14 |
(1.02 to 1.56) | (1.07 to 1.71) | (0.49 to 1.49) |