Review: Low dose thiazides are the most effective first line drugs for hypertension
Wright JM, Lee CH, Chambers GK. Systematic review of
antihypertensive therapies: does the evidence assist in choosing a
first-line drug? CMAJ
1999;161:25-32.
Question
In patients with hypertension, which first line drugs are
effective for reducing death and cardiovascular events?
Data sources
Studies were identified by searching Medline (1966-97), the
Cochrane Library (1998 issue 2), and references of
previous meta-analyses (1980-97).
Study selection
Studies were selected if patients had systolic blood pressure
>=160 mm Hg or diastolic blood pressure >=90 mm Hg; random allocation
was used; a first line antihypertensive drug was compared with another
first line drug or no treatment (including placebo); group baseline
characteristics were reported; end points were defined; >=1 year of
follow up was reported; and >70% of patients were receiving the study
drug after one year. Studies were excluded if antihypertensive drugs
were used for indications other than hypertension.
Data extraction
Two reviewers independently extracted data on patients,
study duration, treatment, outcomes (death, stroke, coronary artery
disease, and total cardiovascular events), and withdrawals because of
adverse effects.
Main results
Altogether 23 studies (50 853 patients) met the inclusion
criteria. Sample sizes ranged from 87-17 354 patients. In
meta-analyses of drug-drug comparisons, no differences existed in
death, stroke, coronary artery disease, or total cardiovascular events.
Fewer withdrawals because of adverse effects occurred with thiazides
than with ² blockers, and in one trial with a calcium-channel blocker
than with an angiotensin converting enzyme inhibitor (see table). In
comparisons of drugs with no treatment, low dose thiazides reduced
death, and thiazides (all doses) and a calcium channel blocker reduced
stroke and total cardiovascular events; only low dose thiazides reduced
coronary artery disease (see
table).
Conclusion
In patients with hypertension, low dose thiazides are effective
for reducing death, stroke, and coronary artery
disease. Funding: British Columbia Ministry of
Health and the University of British Columbia.
Correspondence to: Dr J M Wright, Department of Pharmacology and
Therapeutics, 2176 Health Sciences Mall, University of British
Columbia, Vancouver, British Columbia V6T 1Z3, Canada (Fax
604-822-0701)
EBM-Commentary
Several national guidelines, including the US joint National
Committee on the Prevention, Detection, and Evaluation and Treatment of
Hypertension, 1 have recommended thiazides as first line
antihypertensive therapy. Yet in practice, use of thiazides lags far
behind the newer antihypertensive drugs, even though the effectiveness
of these has been less well shown.
Unfortunately, few direct comparisons have been done among
different classes of antihypertensive drugs. Those comparisons that
have been done were limited to two classes of drugs in any one study,
usually between ² blockers and thiazides. A comparison of several
classes of drugs is now under way in the Antihypertensive and Lipid
Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
study. 2 It is designed to compare the mortality and
cardiovascular outcomes of a relatively high risk group of patients
with hypertension treated with either a thiazide, a calcium-channel
blocker, an ACE inhibitor, or an ± blocker. This large study with
42 451 patients is partially completed, and final results are expected
in two to three years.
As concluded in this and other systematic reviews, low-dose
thiazides should be the first line of treatment for hypertension. Such
treatment reduces not only risk for stroke but also other
cardiovascular morbidity and mortality.
Mohammad G Saklayen Wright State University, Centerville, Ohio, USA
- Arch Intern Med 1997;157:2413-46.
- Davis BR, Cutler JA, Gordon DJ, Furberg CD, Wright JT Jr, Cushman WC, et al. Am J Hypertens 1996;9:342-60.
 |
| Effectiveness of first line antihypertensive drugs for hypertension at up to 10 years |
|
| Comparison |
No of studies |
Outcomes |
Pooled relative risk reduction (%) (95% CI) |
|
| Thiazides v ² blockers |
5 |
Withdrawals because of adverse effects |
31 (24 to 37) |
| Low dose thiazides v no treatment |
5 |
Death |
11 (1 to 19) |
|
|
Stroke |
34 (21 to 44) |
|
|
Coronary artery disease |
29 (16 to 40) |
|
|
Cardiovascular events |
32 (25 to 38) |
| High dose thiazides v no treatment |
11 |
Stroke |
53 (39 to 63) |
|
|
Cardiovascular events |
28 (18 to 37) |
| Calcium channel blockers v no treatment |
1 |
Stroke |
39 (13 to 57)* |
|
|
Cardiovascular events |
39 (13 to 43)* |
|
|
|
Relative risk increase (%) (CI) |
| Angiotensin converting enzyme inhibitors v calcium channel blockers |
1 |
Withdrawals because of adverse effects |
231 (119 to 400)* |
|
| *Not pooled. |
Wright JM, Lee CH, Chambers GK
studentBMJ 2000;08:175-216 June ISSN 0966-6494
