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Initial antihypertensive drug therapy—A comparison of alpha-blocker (prazosin) and diuretic (hydrochlorothiazide)
Initial Antihypertensive Drug Therapy-A Comparison of Alpha-Blocker (Prazosin) and Diuretic (Hydrochlorothiazide) Brief Summary of a Randomized, Controlled Trial* M.A.,JEREMIAH STAMLER, M.D., FLORA C. GOSCH, M.D., DAVID M. BERKSON, M.D., R. DYER, Ph.D.,PATRICIA HERSHINOW, R.N. chmgo,lihno~s
ROSE STAMLER, ALAN
ffect on blood pressure and serum lipid levels was E compared for the alpha-blocker prazosin versus the diuretic hydrochlorothiazide as initial antihypertensive drug treatment for 102 men and women with less severe hypertension (average entry pressure 1481 97 mm Hg, with no major organ system damage) [l]. Patient characteristics are listed in Table I. A twocenter trial randomly assigned patients to treatment with either prazosin or hydrochlorothiazide; the alternate drug was added if adequate blood pressure control was not attained with the originally assigned drug, and treatment was discontinued in patients not able to tolerate a drug. Both drugs were similar in ability to control elevation of diastolic blood pressure (Table II). The mean daily dose of prazosin at the final visit of assigned drug was 8.8 mg per day; three quarters of the patients were receiving 10 mg per day or less. One quarter of those assigned to hydrochlorothiazide were receiving 25 mg per day at the final visit on that drug, whereas three quarters were receiving 50 mg per day. Fewer patients were able to tolerate prazosin than were able to tolerate hydrochlorothiazide (Table III). In this study, after an average of 40 weeks receiv-
TABLE II Blood Pressure at Entry and During Trial with Prazosin and Hydrochlorothiazide* Prazosin (n = 42) Mean basellne(mm Hg) systolic Diastolic Trial average with assigned drug (mm Hg) Systolic Dlastollc
Hydrochlorothiazide (n = 48)
146.0 i 14.3
151.4 _f 16.3
97.8 2 5.4
97.4 + 7.3
134.2 + 15.9 87.0 2 7.0
131.7 i 12.9 87.2 k 8.1
-11.7 t 10.5 -10.8 i 5.3
-19.7 t 14.7 10.2 + 7.9
8.8
438
Change(mm Hg) Systolic
Dlastollc Mean daily dose (mg) L
*Values are mean ? SD (mm Hg) t value for difference between the two groups in change in systolic blood pressure IS equal to 2.90 (p
TABLE Ill Side Effects on Assigned or Combined Medication
TABLE I Prazosin (n = 42)
Patient Characteristics at Baseline* Prazosin (n = 49) Age (years) Male (percent) Cigarette smokers (percent) Black (percent) Serum total cholesterol (mgidl) Serum trigiycerldes jmgidl) Entry diastolic blood pressure (mm Hg) Entry systolic blood pressure (mm Hg) Resting pulse (beatsimlnute) Relative welghtt
Hydrochlorothiazide (n = 53)
51.3 ? 9.7 83.7
51.0 i 11.7 79.2
28.6 32.7 229.6 -t 42.3 173.9i- 79.6 97.6 i 5.4
20.8 15.1 229.4 i 39.4 166.6 ? 120.8 97.4 i 7.5 151.4 + 16.6 74.8 i 12.8 127.5 I 18.6
145.4 ? 13.6
74.5 t 8.2 133.7 5 20.8
Number with complalnts of marked degree Number removed from drug
24
January 23, 1989
The American Journal of Medicme
Combined Therapy (n = 21)
30
7
8
17
3
8
TABLE IV Serum Total Cholesterol Levels at Entry and during Trial with Prazosin and Hydrochlorothiazide*
411values except percent male, percent cigarette smokers, and percent black are pre!nted as mean i- SD. Approximately one half of all patients completed one year or nger; average time on asslgned drug was 40 weeks. ?atto of observed to desrrable weight for height and sex (from 1959 actuarial data).
From the Department of Community Health and Preventive Medlclne, Northwestern Unlverslty Medical School and St. Joseph Hospital, Chlcago, lll~no~s *Material in this article was adapted with permIssion from the American Heart Assoclatlon. Inc. Requests for reprints should be addressed to Prof. Rose Stamler, Department of Communlty Health and Preventive Medicine, Northwestern Unlverslty Medical School, 303 East Chicago Avenue, Chicago, lll~no~s60611.
Hydrochlorothiazide (n = 48)
Prazosin (n = 42)
Hydrochlorothiazide (n = 48)
Baselineaverage (mgidl)
227.7 i 40.5
228.9 i 38.8
Trial average with assigned drug (mgidl)
218.3 ? 38.7
233.9 i 40.8
-9.3 t 18.8
15.0 + 20.3
Change(mgidl)
J
*Values are mean i_ SD (mg/dl). t value for difference between the two groups in change IS equal to 3.50; p
Volume 86 (suppl 16)
SYMPOSIUM
ON CHD AND HYPERTENSION
/ STAMLER ET AL
TABLE V
TABLE VII
Serum Triglyceride Levels at Entry and during Trial with Prazosin and Hydrochlorothiazide*
Effect of Combined Therapy on Serum Cholesterol Levels*
Prazosin (n = 42)
Prazosin (n = 8)
Hydrochlorothiazide (n=48)
BaselIneaverage (mgidl]
168 1 2 n.2
1594 ? 902
Trial average receung assIgned drug (mg/dl)
134.2 * 72.0
178.0 z 87.0
Change (mgidl)
-33.9 -’ 49 2
t18.6 I 398
Asslgned drug (monotherapy) Changefrom baselIne
*Values are mean + SD (mg/dl). t value for difference between the two groups in change IS equa! to 5 51. p
TABLE VI
Baselineaverage (mgidl)
235.1 i 35.5
227.1 2 42.5
Trial average with asslgned drug (mgidl) First SIXmonths Second SIXmonths More than one year
224.7 ? 39.4 218.2 t- 35.8 221.6 * 29.8
238.8 i 53.9 227.2 i 41.4 231.6 i 45.0
t97 t 186
Combined therapy1 Changefrom trial average on assigned drug (monotherapy)
~8.8 i 8.1
-14.4 i- 19.1
Net change from baselIne
-4.1 ? 12.4
-4.7 t 20 8
Sh%%nce in this change between the two groups IS slgnlficant at p c-0.01 (t = 3.72). difference in change from baselme while receiving combined therapy IS not significant’
Long-Term Effects of Treatment on Serum Total Cholesterol Levels* Hydrochlorothiazide (n = 14)
- 12.8 i 13.7
‘Values are mean i- SD (mgidl) tPatlents orlglnally assigned to prazosin therapy had hydrochlorothlazlde added, whereas those orIgInally treated with hydrochlorothiarlde had that drug plus prazosln as combined
T
Prazosin (n = 12)
Hydrochlorothiazide (n = 13)
Net Changet
t22.1 1-16.9 t 18.0
*Values are mean 2 SD (mg/dl). t value for difference between the two groups in change for first SIX months receiving assigned drug 1s equal to 2.58 (p <0.05), for second SIX months IS equal to 198 (p = 1s not slgnlflcant); and for more than one year IS equal to 2 54 (p
ing the assigned drug, a decline was observed in both serum total cholesterol (-9.3 -+ 18.3 mgidl; Table IV) and serum triglyceride (-33.9 2 49.2 mgidl; Table V) levels in prazosm-treated patients. In contrast, an increase in both of these lipids was seen in hydrochlorothiazide-treated patients (+5.0 + 20.3 mgidl for serum total cholesterol and +18.6 4 39.8 mgidl for
serum triglyceride levels). The net trial differences between the groups were 14.3 mgidl for total cholesterol and 52.5 mgidl for triglyceride levels, in favor of prazosin (p ~0.001 for both comparisons). These differences in lipid levels between the two groups persisted into the second year of the trial (p ~0.05; Table VI). There were no significant differences between the drug groups with respect to levels of high-density lipoprotein or its subfractions, or low-density lipoprotein cholesterol. The results of the lipid effects in patients who required a combination of the two drugs to achieve blood pressure control are reported in Table VII. For those able to continue with prazosin, either as the single initial treatment or in combination with hydrochlorothiazide, prazosin therapy appears to be an asset in that it produced no adverse lipid effects.
REFERENCE 1. Stamler R, Stamler J, Gosch FC, Berkson DM. Dyer AR, Hershlnow P: In~bal antlhypertensue drug therapy. FInal report of a randomued, controlled trial comparlng a-blocker and dluretlc Hypertension 1988, 12: 5746581
January 23, 1989
The American Journal of Medune
Volume 86 (suppl 1B)
25
ROSE STAMLER, ALAN
ffect on blood pressure and serum lipid levels was E compared for the alpha-blocker prazosin versus the diuretic hydrochlorothiazide as initial antihypertensive drug treatment for 102 men and women with less severe hypertension (average entry pressure 1481 97 mm Hg, with no major organ system damage) [l]. Patient characteristics are listed in Table I. A twocenter trial randomly assigned patients to treatment with either prazosin or hydrochlorothiazide; the alternate drug was added if adequate blood pressure control was not attained with the originally assigned drug, and treatment was discontinued in patients not able to tolerate a drug. Both drugs were similar in ability to control elevation of diastolic blood pressure (Table II). The mean daily dose of prazosin at the final visit of assigned drug was 8.8 mg per day; three quarters of the patients were receiving 10 mg per day or less. One quarter of those assigned to hydrochlorothiazide were receiving 25 mg per day at the final visit on that drug, whereas three quarters were receiving 50 mg per day. Fewer patients were able to tolerate prazosin than were able to tolerate hydrochlorothiazide (Table III). In this study, after an average of 40 weeks receiv-
TABLE II Blood Pressure at Entry and During Trial with Prazosin and Hydrochlorothiazide* Prazosin (n = 42) Mean basellne(mm Hg) systolic Diastolic Trial average with assigned drug (mm Hg) Systolic Dlastollc
Hydrochlorothiazide (n = 48)
146.0 i 14.3
151.4 _f 16.3
97.8 2 5.4
97.4 + 7.3
134.2 + 15.9 87.0 2 7.0
131.7 i 12.9 87.2 k 8.1
-11.7 t 10.5 -10.8 i 5.3
-19.7 t 14.7 10.2 + 7.9
8.8
438
Change(mm Hg) Systolic
Dlastollc Mean daily dose (mg) L
*Values are mean ? SD (mm Hg) t value for difference between the two groups in change in systolic blood pressure IS equal to 2.90 (p
TABLE Ill Side Effects on Assigned or Combined Medication
TABLE I Prazosin (n = 42)
Patient Characteristics at Baseline* Prazosin (n = 49) Age (years) Male (percent) Cigarette smokers (percent) Black (percent) Serum total cholesterol (mgidl) Serum trigiycerldes jmgidl) Entry diastolic blood pressure (mm Hg) Entry systolic blood pressure (mm Hg) Resting pulse (beatsimlnute) Relative welghtt
Hydrochlorothiazide (n = 53)
51.3 ? 9.7 83.7
51.0 i 11.7 79.2
28.6 32.7 229.6 -t 42.3 173.9i- 79.6 97.6 i 5.4
20.8 15.1 229.4 i 39.4 166.6 ? 120.8 97.4 i 7.5 151.4 + 16.6 74.8 i 12.8 127.5 I 18.6
145.4 ? 13.6
74.5 t 8.2 133.7 5 20.8
Number with complalnts of marked degree Number removed from drug
24
January 23, 1989
The American Journal of Medicme
Combined Therapy (n = 21)
30
7
8
17
3
8
TABLE IV Serum Total Cholesterol Levels at Entry and during Trial with Prazosin and Hydrochlorothiazide*
411values except percent male, percent cigarette smokers, and percent black are pre!nted as mean i- SD. Approximately one half of all patients completed one year or nger; average time on asslgned drug was 40 weeks. ?atto of observed to desrrable weight for height and sex (from 1959 actuarial data).
From the Department of Community Health and Preventive Medlclne, Northwestern Unlverslty Medical School and St. Joseph Hospital, Chlcago, lll~no~s *Material in this article was adapted with permIssion from the American Heart Assoclatlon. Inc. Requests for reprints should be addressed to Prof. Rose Stamler, Department of Communlty Health and Preventive Medicine, Northwestern Unlverslty Medical School, 303 East Chicago Avenue, Chicago, lll~no~s60611.
Hydrochlorothiazide (n = 48)
Prazosin (n = 42)
Hydrochlorothiazide (n = 48)
Baselineaverage (mgidl)
227.7 i 40.5
228.9 i 38.8
Trial average with assigned drug (mgidl)
218.3 ? 38.7
233.9 i 40.8
-9.3 t 18.8
15.0 + 20.3
Change(mgidl)
J
*Values are mean i_ SD (mg/dl). t value for difference between the two groups in change IS equal to 3.50; p
Volume 86 (suppl 16)
SYMPOSIUM
ON CHD AND HYPERTENSION
/ STAMLER ET AL
TABLE V
TABLE VII
Serum Triglyceride Levels at Entry and during Trial with Prazosin and Hydrochlorothiazide*
Effect of Combined Therapy on Serum Cholesterol Levels*
Prazosin (n = 42)
Prazosin (n = 8)
Hydrochlorothiazide (n=48)
BaselIneaverage (mgidl]
168 1 2 n.2
1594 ? 902
Trial average receung assIgned drug (mg/dl)
134.2 * 72.0
178.0 z 87.0
Change (mgidl)
-33.9 -’ 49 2
t18.6 I 398
Asslgned drug (monotherapy) Changefrom baselIne
*Values are mean + SD (mg/dl). t value for difference between the two groups in change IS equa! to 5 51. p
TABLE VI
Baselineaverage (mgidl)
235.1 i 35.5
227.1 2 42.5
Trial average with asslgned drug (mgidl) First SIXmonths Second SIXmonths More than one year
224.7 ? 39.4 218.2 t- 35.8 221.6 * 29.8
238.8 i 53.9 227.2 i 41.4 231.6 i 45.0
t97 t 186
Combined therapy1 Changefrom trial average on assigned drug (monotherapy)
~8.8 i 8.1
-14.4 i- 19.1
Net change from baselIne
-4.1 ? 12.4
-4.7 t 20 8
Sh%%nce in this change between the two groups IS slgnlficant at p c-0.01 (t = 3.72). difference in change from baselme while receiving combined therapy IS not significant’
Long-Term Effects of Treatment on Serum Total Cholesterol Levels* Hydrochlorothiazide (n = 14)
- 12.8 i 13.7
‘Values are mean i- SD (mgidl) tPatlents orlglnally assigned to prazosin therapy had hydrochlorothlazlde added, whereas those orIgInally treated with hydrochlorothiarlde had that drug plus prazosln as combined
T
Prazosin (n = 12)
Hydrochlorothiazide (n = 13)
Net Changet
t22.1 1-16.9 t 18.0
*Values are mean 2 SD (mg/dl). t value for difference between the two groups in change for first SIX months receiving assigned drug 1s equal to 2.58 (p <0.05), for second SIX months IS equal to 198 (p = 1s not slgnlflcant); and for more than one year IS equal to 2 54 (p
ing the assigned drug, a decline was observed in both serum total cholesterol (-9.3 -+ 18.3 mgidl; Table IV) and serum triglyceride (-33.9 2 49.2 mgidl; Table V) levels in prazosm-treated patients. In contrast, an increase in both of these lipids was seen in hydrochlorothiazide-treated patients (+5.0 + 20.3 mgidl for serum total cholesterol and +18.6 4 39.8 mgidl for
serum triglyceride levels). The net trial differences between the groups were 14.3 mgidl for total cholesterol and 52.5 mgidl for triglyceride levels, in favor of prazosin (p ~0.001 for both comparisons). These differences in lipid levels between the two groups persisted into the second year of the trial (p ~0.05; Table VI). There were no significant differences between the drug groups with respect to levels of high-density lipoprotein or its subfractions, or low-density lipoprotein cholesterol. The results of the lipid effects in patients who required a combination of the two drugs to achieve blood pressure control are reported in Table VII. For those able to continue with prazosin, either as the single initial treatment or in combination with hydrochlorothiazide, prazosin therapy appears to be an asset in that it produced no adverse lipid effects.
REFERENCE 1. Stamler R, Stamler J, Gosch FC, Berkson DM. Dyer AR, Hershlnow P: In~bal antlhypertensue drug therapy. FInal report of a randomued, controlled trial comparlng a-blocker and dluretlc Hypertension 1988, 12: 5746581
January 23, 1989
The American Journal of Medune
Volume 86 (suppl 1B)
25