Evidence Table 20

Adverse events in head-to-head trials of beta blockers for hypertension

TrialInterventionsSample sizeTrial durationPopulation characteristicsQualityResults
Foerster
1985
Atenolol (ate) 100 mg
Pindolol SR (pin-SR) 20 mg
10724 weeksMean age=41.4
65.4% male
Good
Designed specifically for AE assessment
Changes of >1 cm on VAS interpreted as AE
Data for weeks 13–24(% patients):
n: ate=53; pin=54
Sleep disturbance: ate=18; pin=44(P=0.01)
Dreams: ate=16; pin=15
Fatigue: ate=28; pin=22
Raynaud's phenomenon: ate=14; pin=26
Muscle cramps: ate=12; pin=20
Sexual disturbance: ate=14; pin=8
GI disturbances: ate=21; pin=20
Fogari
1999
Atenolol (ate) 100 mg
Bisprolol (bis) 10 mg
Celiprolol (cel) 400 mg
Propranolol (pro) 160 mg
15218 months100% male
Mean age=52
FairOverall AE incidence(# pts; %): pro=6/37(16.2%); ate=5/38(13.1%); bis=4/39(10.2%)
Lithell
1987
Atenolol (ate) 50 mg
Bisoprolol (bis1) 5 mg
Bisoprolol (bis2) 10 mg
2926 months59.9% male
Mean age=52.6
FairWithdrawals due to adverse events (# patients/%):
ate=2/97(2.1%); bis1=4/97(4.1%); bis2=4/98(4.1%)
Walle
1994
Metoprolol CR 100 mg
Atenolol 100 mg
586 weeks43.3% male
Mean age=58
FairOverall AEs: no differences (data NR)
Serious AEs: meto vs ate = 0 vs 2 (3.3%) (bradycardia and syncope; both leading to withdrawal)
Sundar
1991
atenolol: 100mg
propranolol: 80mg
264 weeks100% male
Mean age=NR
Poorate vs pro (%)
headache: 0 vs 0
weakness: 10.5 vs 10.7
warmth: 2.6 vs 0
oedema: 0 vs 0
dyspnoea: 5.3 vs 0
constipation: 0 vs 0
Steiner
1990
Propranolol 80–240mg (mean=133.4mg per day)
Atenolol 50–100mg (mean=56.4mg per day)
pro: 73
ate: 78
4 weeks100% male
Mean age=NR
Fairpro(%) vs ate(%), all NS
Bradycardia: 4(4.5) vs 9(10)
Gastrointestinal distress: 9(10.1) vs 7(7.8)
Dry mouth: 5(5.6) vs 4(4.4)
Anxiety: 7(7.9) vs 2(2.2)
Sleep disturbance: 4(4.5) vs 6(6.7)
Libido decreased/impotence: 8(9): 5(5.6)
Weakness/fatigue: 15(16.9) vs 8(8.9)
Headache: 12(13.5) vs 9(10)
Total: 57(64) vs 50(55.6)
Withdrawals due to adverse events:
pro: 5(6.85); ate: 0(0)
Dahlof
1988
atenolol 50 mg
metoprolol CR 100 mg
746 weeks51(66%) male
Mean age=54.4
FairSubjective symptoms- leg fatigue, constipation, diarrhoea, bradycardia, cold hands and feet, heavy breathing: NS
Palpitation: meto> ate, P<0.05
Withdrawals due to adverse events: 2(2.6%)
Blumenthal
1988
atenolol 50–100mg
propranolol: 40–80mg
262 weeks100% male
Mean age=42.5
Poorsleep items: NS
sexual functioning: NS
energy: 4 (ate) and 4 (pro) reported being more tired in the morning, while 6 (pla) reported less fatigue.
Buhler
1986
Bisoprolol 10–20mg
Atenolol 50–100 mg
1048 weeks82.7% male
Mean age=53.8
FairBaseline:bis / baseline:ate (number), all NS
headache- 20:7/ 19:9
tiredness- 17:20/ 17:13
Nervousness- 17:10/ 10:8
Sleep problems- 18:11/ 15:10
Cold extremities- 14:13/ 16:12
Sweating- 12:9/ 11:11
Tingling sensations- 12:6/ 9:5
Feeling of weakness- 11:6/ 5:7
Dizziness- 11:3/ 8:7
Joint pain- 9:9/ 6:8
Depressed mood- 12:11/ 9:5
Sex problems- 5:7/ 6:4
Withdrawals due to adverse events:
bis (1): dizziness
ate (5): diarrhea, skin rash, asthmatic bronchitis, vertigo, headache
Brixius
2007
Group A: nebivolol (neb) 5 mg daily X 12 weeks, once daily placebo x 2 weeks, metropolol succinate 95 mg daily x 12 weeks.

Group B: metropolol succinate 95 mg daily x 12 weeks, once daily placebo x 2 weeks, nebivolol (neb) 5 mg daily X 12 weeks
4828 weeksmean age: group A
48.4; group B 47.2
Male: 100%
Ethnicity: NR
Fair/ poorNo AE reported
”No critical findings regarding safety issues occurred during the study. The results of safety analysis confirmed a good safety profile for both study drugs.”
Yilmaz
2008
Nebivolol (neb) starting dose of 2.5 mg once daily titrated to achieve target DBP of <90 mmHg and SBP of <140 mmHg.

Metoprolol succinate (extended release) starting dose of 25 mg once daily titrated to achieve target DBP of <90 mmHg and SBP of <140 mmHg.

If after 2 weeks BP was normalized, amlodipine (5–10 mg daily) was added to treatment.

Duration: x 6 weeks.
466 weeksBaseline characteristics for patients who completed the study only.
Mean age: 40.7
Male: 20/39 (51%)
Ethnicity: NR
FairNo AE reported

From: Evidence Tables

Cover of Drug Class Review: Beta Adrenergic Blockers
Drug Class Review: Beta Adrenergic Blockers: Final Report Update 4 [Internet].
Helfand M, Peterson K, Christensen V, et al.
Portland (OR): Oregon Health & Science University; 2009 Jul.
Copyright © 2009, Oregon Health & Science University, Portland, Oregon.

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