Table. Studies on the Harms of Early Treatment of High Blood Pressurea
| Author, Year (Reference) |
Study Objective |
Sample Characteristics |
Inclusion Criteria |
Design | Study Groups |
| Fogari, et al., 20018 |
To evaluate the effects of valsartan and carvedilol on sexual function in men |
n=160
Age: 40-49 y
All married |
Newly diagnosed hypertension
Men never treated for hypertension
DBP >95 but <110 mm Hg
No sexual dysfunction |
RCT |
120 patients received carvedilol or valsartan for 16 wk, followed by 4 wk of placebo; they then "crossed over" to alternative regimen for another 16 wk.
40 patients received only placebo |
| Hollenberg, et al., 20039 |
To evaluate symptom distress associated with eplerenone compared with amlodipine |
n=269
Mean age:
67 y, eplerenone group;
69 y, amlodipine group
White: 89% |
Age >50 y
Men and women
Untreated SBP 140-190 mm Hg |
Randomized trial |
134 patients received eplerenone
135 patients received amlodipine
Patients were followed for 24 wk; QOL measures at 14 and 24 wk were SF-36 Health Survey (8 aspects of health-related QOLb), Symptom Distress Index (73 items), and Cantril's Ladder (0-10 ladder grade of QOL) |
| White, et al., 20045 |
To determine whether extended-release diltiazem at bedtime is superior to ramipril at bedtime for control of early-morning BP |
n=261
Mean age: 54 y
Men: 61%
White: 93% |
DBP 90-110 mm Hg during run-in placebo period
Patients with history of CAD, stroke, CHF, secondary hypertension, cardiac conduction abnormalities, poorly controlled DM, malabsorption, or CRF were excluded |
Multicenter randomized trial in the United States and Canada |
Extended-release diltiazem, 240, 360, or 540 mg at bedtime
Ramipril, 5, 10, or 20 mg at bedtime
2-wk prestudy washout of hypertension medications, 3- to 4-wk placebo run-in, then 10 wk of treatment |
| Julius, et al., 20066 |
To examine whether treatment of prehypertension with candesartan prevents or postpones stage 1 hypertension |
n=809
Mean age: 48 y
Men: 59%-60%
White: 80%-84%
Mean BMI: 30 kg/m2 |
Age 30-65 y
Not receiving treatment for hypertension
Average BP: SBP, 130-139 mm
Hg; DBP <89 mm Hg |
Multicenter double-blind RCT in the United States |
Placebo for 4 y
Candesartan, 16 mg, for 2 y,
then placebo for 2 y
3-wk run-in period
If hypertension developed, patients were given metoprolol or hydrochlorothiazide |
| Ebbs, 20017 |
To determine whether ambulatory BP monitoring can assess the effectiveness of selected antihypertensives in maintaining 24-hour BP control |
n=204
Mean age: 54-58 y
Men: 43%-48%
White: 99%
Mean BP:
SBP, 152-161 mm Hg;
DBP, 97-100 mm Hg |
DBP 95-110 mm Hg
Patients with treatment for hypertension, symptomatic CVD, end-organ damage, secondary or malignant hypertension, intolerance of study medications, hypercholesterolemia, type 1 DM, renal impairment, or pregnancy were excluded |
Multicenter randomized trial in the United Kingdom |
1) Doxazosin, 1, 2, or 4 mg
2) Amlodipine, 5 or 10 mg
3) Enalapril, 5, 10, or 20 mg
4) Bendrofluazide, 2.5 or 5 mg
8-wk placebo run-in period
Treatment for up to 14 wk and titrated to achieve BP control and then treatment for another 8 wk |
| Author, Year (Reference) |
Comparison of Groups and Withdrawals |
Main Results |
Adverse Events |
Summary |
| Fogari, et al., 20018 |
6 patients were lost to follow-up: 2 had hypotension, and 4 in placebo group had hypertension >110 mm Hg |
Mean number of intercourse episodes:
At 4 wk: reduced by 43% with carvedilol and by 20% with valsartan (P < 0.05)
At 16 wk: reduced by 50% with carvedilol but increased by 19% with valsartan |
Erectile dysfunction:
15 patients (13.5%) receiving carvedilol
1 patient receiving valsartan and 1 receiving placebo (P < 0.001) |
Carvedilol produced a decline in sexual function (decreased frequency of sexual activity and increased number of patients who had sexual dysfunction).
Valsartan produced a temporary, nonsignificant decline in sexual function and improved function with ongoing treatment.
The drugs did not differ in terms of BP control. |
| Hollenberg, et al., 20039 |
Groups did not differ in age, sex, ethnicity, employment, initial QOL, or baseline BP
Dropout rates did not differ by group but were higher for amlodipine (30 patients [25%]) than eplerenone (19 patients [16%]) |
Average decrease in Symptom Distress Index score with amlodipine and increase in score for eplerenone (P = 0.03); 36 of 73 symptoms favored eplerenone, and 1 favored amlodipine
No significant differences in SF-36 Health Survey results
Amlodipine was significantly associated with ankle swelling, headache, facial flushing, constipation, and pronounced heartbeat
Both drugs decreased SBP; amlodipine significantly decreased DBP |
No eplerenone side effects related to an action on steroid receptors
No cases of gynecomastia, tender breasts, or menstrual irregularities
Edema: 25% with amlodipine vs. 5% with eplerenone |
Amlodipine was associated with annoying but not life-threatening side effects. |
| White, et al., 20045 |
90% of diltiazem recipients and 92% of ramipril recipients completed the study
AEs were the most common reason for dropping out |
Diltiazem reduced early morning BP to a greater extent than ramipril (-18/-15 mm Hg vs. -13/-8 mm Hg; P < 0.001) |
>1 AE occurred in 50% of diltiazem recipients and 40% of ramipril recipients
No deaths
Withdrawals:
3 patients with serious AE: 1 during placebo run-in, 1 in diltiazem group (facial/peripheral edema), 1 in ramipril group (severe UTI)
Most common reason for withdrawal: leg edema with diltiazem (3%), cough with ramipril (2%)
Other AEs:
Ramipril:
cough (8%)
headache (12%)
lower-extremity edema (2%)
Diltiazem:
cough (0.8%)
headache (5%)
lower-extremity edema (13%) |
AEs were very common (40%-50% of patients)
with both drugs.
Serious AEs were uncommon (2%-3%), and 2 of the 3 reported were probably not related to the drug. |
| Julius, et al., 20066 |
- |
Candesartan significantly decreased risk for hypertension at the end of 4 y (relative risk, 0.84) |
Serious AEs: 3.5% of candesartan recipients, 5.9% of placebo recipients
Other AEs: 89% of candesartan recipients, 88.5% of placebo recipients
AEs with higher rate with candesartan vs. placebo:
Headache: 21.5%
URI: 14.4%
Nasopharyngitis: 10%
Dizziness: 10%
Fatigue: 8.1%
Pain in extremity: 7.6%
Insomnia: 5.6%
Anxiety: 5.6%
Hypotension: 1%
Syncope: 0.5% |
AEs were very common (about 89% of participants).
Serious AEs were uncommon (3.5% of candesartan recipients). |
| Ebbs, 20017 |
- |
24-h ambulatory SBP and DBP decreased in all groups; no significant differences among groups |
74% of participants reported an AE
Withdrawals: 11% overall owing to an AE
Most common AE: headache (20%) |
AEs were very common (74%); the most common AE was headache.
Serious AEs were uncommon (11%). |
a. AE = adverse effect; BMI = body mass index; BP = blood pressure; CAD = coronary artery disease; CHF = congestive heart failure; CRF = chronic renal failure;
CVD = cardiovascular disease; DBP = diastolic blood pressure; DM = diabetes mellitus; QOL = quality of life; RCT = randomized, controlled trial; SBP = systolic blood pressure; SF-36 = Short Form-36; URI = upper respiratory tract infection; UTI = urinary tract infection.
b. The 8 aspects of health-related QOL are physical function, role—physical, bodily pain, general health, vitality, social functioning, role—emotion, and mental health.
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