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Spironolactone and altizide in systemic hypertension: Ambulatory multicenter study
Spironolactone and Altizide in Systemic Hypertension: Ambulatory Multicenter Study Jacques Sternon, MD
A multicenter study was performed in 919 hypertensive patients, 780 of whom could be evaluated. Patients in group I (n = 482) were treated with Aldactaziw alone (altizide + spironolactone, 2 tablets per day). The other 298 patlents (group II) were treated with 1 or 2 tablets per day of Aldactazhre plus a conventlonal antihypertenslve agent, e.g., a @bloclcer, cu-methyldopa or donidine. After 45 days of treatment with Aldactazine alone, mean systolii and dbstolk blood pressure (BP) decreased by 15 and 14%, respectively, VI baseline values. The addition of the other antihypertensive agent decreased BP further; however, the best results were obtained with the combination of Aldactazine and clonidine. With this combination, systolk and diastolic BP decreased by 16.6 and lS%, respectively, vs baseline. In terms of adverse effects, a few cases of gastrointestinal disturbances and orthosbtlc hypotension were reported. (Am J Cardid lSSO;65:24K-27K)
hiazide diuretics have long been used as tirstline pharmacologic therapy of essential hypertension.’ However, they have been associated with a number of metabolic adverse effects such as hyperglycemia, hyperuricemia, hypertriglyceridemia, decreased high-density lipoprotein cholesterol, hypokalemia and hypomagnesemia.2-4 This has resulted in increased interest in potassiumsparing diuretics, particularly when combined with a thiazide diuretic, because this type of combination appears to be more devoid of metabolic consequences than the thiazides alone.5,6 This study was conducted to assessthe efficacy of an aldosterone antagonist-altizide combination (Aldactazinc@) and to compare its sole use vs its use with other antihypertensive agents in patients with essential hypertension.
T
METHODS Patientrr: Patients considered for the study were male
and female ambulatory patients, 20 to 85 years old, with essential hypertension (systolic and diastolic blood presTABLE
I Therapeutic
Regimens Aldactazine
Add-On Antihypertensive @blocker a-Methyldopa Clonidine Other Total
(1 tab/day)
Total No. of Pts.
(2 tab/day)
42 13 21
83 42 31 55
125 53 44 76
a7
211
298
11
tab = tablet.
TABLE II Discontinuations,
Protocol
Violations,
Adverse
Effects* Adverse Effects
Group I
(n = 31)
(n = 16)
(n = 15)
GI disturbances
4 4 3 3
6 3 -
Syncope
From the ULB, Brussels, Belgium. Address for reprints: Jacques Sternon, MD, HBpital Universitaire Erasme, Service de Medicine Interne, Route de Lennik, 808, 1070 Bruxelles, Belgium.
24K
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
65
Pollakiuria Headaches Muscle cramps Pruritus Lumbar pain Constipation Diarrhea Dry mouth * Protocol violations/dropouts GI = gastrointestinal
Group II
1 1 1
1 1 1 1
-
-
1
(n = 107)
2
Cl TABLE
III Group
BP = blood
TABLE Values
I
I: Distribution
of Systolic
Blood
TABLE
Pressure
VI Group
I: Improvement
pressure:
IV Group
TABLE V Group After Monotherapy Approximation)*
80 90 100 110 120 130 140 150
Syst = systok
I: Distribution
BP (mm W
of Diastolic
Blood
Pressure
I
78.8 83.8 88.2 92.5 96.6 100.6 104.4 108.0
mm Hg
No. of %
PtS.
I: Improvement in Systolic Blood with Aldactazine (Statistical
I
Pressure
135 1 150
160
170
180 190 Day 0
Day 45 Day 0 Systolic BP (mm W
190 200 210 220
Blood Pressure
Day 0 (mm Hg)
Diast
150 160 170 180
in Diastolic
20-39
Years
40-59
Years
60-89
Years
(2 tab/day)
(2 tab/day)
(2 tab/day)
138.7 142.8 14-6.7 150.5 154.2 157.7 161.2 164.6
140.5 144.7 148.6 152.5
142.2 146.4 150.4 154.3 158.1 161.7 165.3 168.8
156.2 159.8 163.3 166.7
FIGURE
I
A 60-89
years
1 40-59
years
0 20-39
years
200
210
220
mmHg
1. Systolic blood pressure. mm Hg 150 140 130 1
1 i Day 45
sure [BP] 1150 and 195 mm Hg, respectively). All patients gave informed consent. Criteria: Patients with kidney failure, anuria, hyperkalemia, hypersensitivity to thiazide diuretics, and pregnant or nursing women were excluded from the study. Dosage and monitoring: The study comprised 2 groups: group I (Aldactazine as monotherapy)tablets of Aldactazine per day with breakfast. Group II (combination therapy)-1 or 2 tablets of Aldactazine per day plus either a fi blocker, a-methyldopa, clonidine, or other antihypertensive agent that the patient may have been using. Serial BP (seated) measurements were obtained by the same investigator after 15 and 45 days of treatment (control visits). Heart rate and adverse effects were similarly recorded. Patient distribution: Initially, 919 patients were enrolled in the study. They were divided into 2 groups: (1) Group I was a monotherapy group consisting of 590
120
80
90
100
110
120
130
140
150mmHg
Day 0
FIGURE
2. Diastolii
blood
pressure.
patients treated with 2 tablets of Aldactazine per day; of these, 482 came back for the 2 follow-up visits (Table I). (2) Group II was a combination therapy group consisting of 329 patients who received Aldactazine (1 or 2 tablets per day) plus either a P blocker, cY-methyldopa, clonidine or another antihypertensive. Within group II, 298 patients came to the 2 follow-up visits (Table I). THE AMERICAN
JOURNAL
OF CARDIOLOGY
JUNE 19. 1990
25K
ROLE OF ALDOSTERONE
A SYMPOSlUM:
ALDOSTERONE
AND
mm Hg
Diastolic BP (mm fig)
130 120
A 60-89 I 40-59 0 20-39
110
90
595 96-104 105-119 1120 Total %
mm Hg
RGURE
115
130
3. Double
145
160
175 Day 0
190
205
220
235
product.
20-39Years
3 11 4 2 20 15.4
195 96-104 105-119 2120 Total %
40-59
Years
Aldactazine
60-89
Years
Total
%
0 2 1 0 3 5.7
4 7 3 1 15 12
3 36 25 4 68 54.40
0 3 0 0 3 6
Total
%
Dose
3 19 13 7 42 32.3
14 47 42 27 130
10.8 36.1 32.3 20.8 100
(750
mg/day)
8 7 7 7 29 54.7
9 16 17 11 53
17.0 30.2 32.1 20.8 100
+ B Blocker 1 19 17 5 42 33.60
Aldactazine 5159 160-184 185-214 2215 Total %
60-89Years Middle-Sized
+ wMethyldopa 1 7 9 4 21 39.6
Aldactazine 5159 la-184 185-214 2215 Total %
40-59Years + /3 Blocker, 8 17 25 18 68 52.3
Aldactazine
TABLE VI! Group II: Age-Related Distribution of Systolic Blood Pressure Values in Each Therapeutic Subgroup Systolic BP (mm Hg)
20-39Years AJdactazine
years years years
100 100
MEDICINE
IN CARMOVASCULAR
TABLE VIII Group II: Age-Related Distribution of Diastolic Blood Pressure Values in Each Therapeutic Subgroup
160
$ $
ANTAGONISM
8 62 45 10 125
6.4 49.60 36.00 8.00 100
%
+ wMethyldopa
0 12 7 2 21 39.6
0 13 11 5 29 54.7
Aldactazine
595 96-104 105-119 2120 Total
0 0 1 1 2 4.5
+ Clonidine 2 0 7 5 14 31.8
(450
pg/day)
3 6 12 7 28 63.6
5 6 20 13 44
11.4 13.6 45.4 29.5 100
I 0 28 18 7 53
0 52.8 34.0 13.2 100
+ Clonidine
BP = blood pressure.
Statistical evaluation: Statistical analysis was performed on the variations in systolic and diastolic BP values on day 0 and day 45 for 780 patients divided into 2 groups (monotherapy and add-on therapy). RESULTS Group
Of the initial 919 patients, 3 1 withdrew from the study because of adverse effects ( 16 from group I and 15 from group II). In addition, 107 patients were withdrawn from the study for protocol violations (Table II). TABLE
IX Percent
Change
in Blood
Pressure
at Day 45 vs Day 0 Systolic
Group I Aldact Group II B blocker o-methyldopa Clonidine Other
alone
Diastolic
BP
THE AMERICAN
JOURNAL
BP
Mean (W
Range* (X0)
No. of
Mean w
Range* W)
No. of
PtS.
14.3
13.6-15.0
482
13.4
12.7-14.1
498
15.4 16.0 16.6 12.9
12xX17.0 13.9-18.2 13.5-19.6 11.0-14.7
125 53 44 75
15.5 14.5 18 14.8
13817.2 11.2-17.6 14.4-21.6 12.7-16.8
130 53 44 76
* 95% confidence interval. Aldact = Aldactazine; BP = blood pressure.
26K
I (monothwapy): Baseline systolic BP varied between 160 and 210 mm Hg in 83% of the cases (Table III). Baseline diastolic BP ranged between 95 and 116 mm Hg in 81% of the patients (Table IV). There was a marked reduction in systolic BP between day 0 and day 45. The variations in systolic BP between day 0 and day 45, broken down by age group, are listed in Table V. The systolic BP profiles between day 0 and day 45 were parallel for the various age groups, with the lower readings, as expected, in the younger age group (Fig. 1).
OF CARDIOLOGY
VOLUME
65
PtS.
Diastolic pressure decreased greatly between day 0 and day 45 (Table VI). The statistical analysis of diastolic BP variations confirmed this decrease (Fig. 2). Diastolic BP values were not broken down into the different age groups. Statistical analysis showed that age had an effect on double product (systolic BP X heart rate) as well (Fig. 3). The best results were obtained in hypertensive patients older than 60 years. Group II (combination therapy): Tables VII and VIII show the distribution of BP values as a function of age in the 3 therapeutic subgroups (Aldactazine + /3 blocker, Aldactazine + a-methyldopa, and Aldactazine + clonidine). Both systolic and diastolic BP decreased very markedly between day 0 and day 45. Statistical analysis shows the benefits of the combination of Aldactazine and the various antihypertensive agents (B blocker, methyldopa, or clonidine) vs monotherapy with Aldactazine alone (Table IX). Although significance could not be determined because of the lack of a suitable control group, the combination of Aldactazine and clonidine was especially effective, particularly since the patients in this subgroup ‘ABLE
X
5 and
Day
Percent
Change
in Double
Product
Between
Day
0
Group I Aldact Group II fl blocker a-methyldopa Clonidine Other
alone
Mean (%)
Range* W)
No. of Pk.
17.2
16.1-18.3
488
24.1 21 .o 20.0 17.4
21.3-26.8 17.9-23.9 15.1-24.6 14.2-20.5
114 45 36 69
* (I=.% r,,r%fd~nr~ in+o.n,;.,
TABLE
XI Adverse
Effects
with
Each
Therapeutic
were older and had relatively higher BP levels than those in the other subgroups (Table IX). The statistical analysis of the double product showed that combination therapy, especially Aldactazine plus p blocker, was particularly effective, presumably because of the bradycardiac effect of the /3 blocker (Table X). ADVERSE EFFECTS A number of minor adverse effects were recorded in each group, consisting mostly of gastrointestinal disturbances and orthostatic hypotension (Table XI). One patient with gout in group I had an attack during the treatment period. CONCLUSIONS
Although the absence of a control group precluded calculations of statistical significance, the results of this large multicenter study demonstrate that a combination product of aldosterone antagonist (spironolactone) is both safe and effective in the treatment of hypertension, whether used alone or when combined with other “addon” antihypertensive agents (B blockers, methyldopa, clonidine). REFERENCES 1. Joint National Committee. The 1988 report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure. ,&C/I lnrern Med 1988:148:1023-1038. 2. Dreslinski GR, Frohlich ED, Messerli FH, Batson HM. Diuretics. fracrical Cardiology I 980,6:132m14S. 3. Hollitield JW. Thiazide treatment of hypertension: effects of thiazide diuretics on serum potassium, magnesium, and ventricular ectopy. Am J Med /986;80: suppl4A:8-12. 4. Whang R. Magnesium deficiency: pathogenesis, prevalence, and clinical implications. Am J Med 1987:72:suppl 3A:24&29. 5. Dyckner T, Wester PO. Potassium/magnesium depletion in patients with cardiovascular disease. Am J Med 1987;82:.wppl 3A:ll-17. 6. Muller J. Spironolactone in the management of congestive cardiac failure: a review. Clin Ther 1986:9x53-76.
Regimen Group II Combination Add-On (293
Group I Monotherapy (482 Patients): Aldactazine
fl Blocker
a-Methyldopa
Clonidine
GI disturbances Orthostatic hypotension Weakness Muscle cramps Headache Pollakiuria
18 16 8 4 3 2
6 7 1 3 3 -
2 1 1 -
3 2 1 1
Gynecomastia. mild Thirst K+t K+i Dry mouth Diarrhea Constipation Sleep disturbances Skin rash Visual disturbances Gout
2 1 1 1
1 -
1 1 -
1
Adverse
Effects
GI = gastrointestinal:
K+tl = potassium
1 1 1 1 increased
Therapy Patients)
-
and decreased.
THE AMERICAN
JOURNAL
OF CARDIOLOGY
JUNE
19,
1990
27K
A multicenter study was performed in 919 hypertensive patients, 780 of whom could be evaluated. Patients in group I (n = 482) were treated with Aldactaziw alone (altizide + spironolactone, 2 tablets per day). The other 298 patlents (group II) were treated with 1 or 2 tablets per day of Aldactazhre plus a conventlonal antihypertenslve agent, e.g., a @bloclcer, cu-methyldopa or donidine. After 45 days of treatment with Aldactazine alone, mean systolii and dbstolk blood pressure (BP) decreased by 15 and 14%, respectively, VI baseline values. The addition of the other antihypertensive agent decreased BP further; however, the best results were obtained with the combination of Aldactazine and clonidine. With this combination, systolk and diastolic BP decreased by 16.6 and lS%, respectively, vs baseline. In terms of adverse effects, a few cases of gastrointestinal disturbances and orthosbtlc hypotension were reported. (Am J Cardid lSSO;65:24K-27K)
hiazide diuretics have long been used as tirstline pharmacologic therapy of essential hypertension.’ However, they have been associated with a number of metabolic adverse effects such as hyperglycemia, hyperuricemia, hypertriglyceridemia, decreased high-density lipoprotein cholesterol, hypokalemia and hypomagnesemia.2-4 This has resulted in increased interest in potassiumsparing diuretics, particularly when combined with a thiazide diuretic, because this type of combination appears to be more devoid of metabolic consequences than the thiazides alone.5,6 This study was conducted to assessthe efficacy of an aldosterone antagonist-altizide combination (Aldactazinc@) and to compare its sole use vs its use with other antihypertensive agents in patients with essential hypertension.
T
METHODS Patientrr: Patients considered for the study were male
and female ambulatory patients, 20 to 85 years old, with essential hypertension (systolic and diastolic blood presTABLE
I Therapeutic
Regimens Aldactazine
Add-On Antihypertensive @blocker a-Methyldopa Clonidine Other Total
(1 tab/day)
Total No. of Pts.
(2 tab/day)
42 13 21
83 42 31 55
125 53 44 76
a7
211
298
11
tab = tablet.
TABLE II Discontinuations,
Protocol
Violations,
Adverse
Effects* Adverse Effects
Group I
(n = 31)
(n = 16)
(n = 15)
GI disturbances
4 4 3 3
6 3 -
Syncope
From the ULB, Brussels, Belgium. Address for reprints: Jacques Sternon, MD, HBpital Universitaire Erasme, Service de Medicine Interne, Route de Lennik, 808, 1070 Bruxelles, Belgium.
24K
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
65
Pollakiuria Headaches Muscle cramps Pruritus Lumbar pain Constipation Diarrhea Dry mouth * Protocol violations/dropouts GI = gastrointestinal
Group II
1 1 1
1 1 1 1
-
-
1
(n = 107)
2
Cl TABLE
III Group
BP = blood
TABLE Values
I
I: Distribution
of Systolic
Blood
TABLE
Pressure
VI Group
I: Improvement
pressure:
IV Group
TABLE V Group After Monotherapy Approximation)*
80 90 100 110 120 130 140 150
Syst = systok
I: Distribution
BP (mm W
of Diastolic
Blood
Pressure
I
78.8 83.8 88.2 92.5 96.6 100.6 104.4 108.0
mm Hg
No. of %
PtS.
I: Improvement in Systolic Blood with Aldactazine (Statistical
I
Pressure
135 1 150
160
170
180 190 Day 0
Day 45 Day 0 Systolic BP (mm W
190 200 210 220
Blood Pressure
Day 0 (mm Hg)
Diast
150 160 170 180
in Diastolic
20-39
Years
40-59
Years
60-89
Years
(2 tab/day)
(2 tab/day)
(2 tab/day)
138.7 142.8 14-6.7 150.5 154.2 157.7 161.2 164.6
140.5 144.7 148.6 152.5
142.2 146.4 150.4 154.3 158.1 161.7 165.3 168.8
156.2 159.8 163.3 166.7
FIGURE
I
A 60-89
years
1 40-59
years
0 20-39
years
200
210
220
mmHg
1. Systolic blood pressure. mm Hg 150 140 130 1
1 i Day 45
sure [BP] 1150 and 195 mm Hg, respectively). All patients gave informed consent. Criteria: Patients with kidney failure, anuria, hyperkalemia, hypersensitivity to thiazide diuretics, and pregnant or nursing women were excluded from the study. Dosage and monitoring: The study comprised 2 groups: group I (Aldactazine as monotherapy)tablets of Aldactazine per day with breakfast. Group II (combination therapy)-1 or 2 tablets of Aldactazine per day plus either a fi blocker, a-methyldopa, clonidine, or other antihypertensive agent that the patient may have been using. Serial BP (seated) measurements were obtained by the same investigator after 15 and 45 days of treatment (control visits). Heart rate and adverse effects were similarly recorded. Patient distribution: Initially, 919 patients were enrolled in the study. They were divided into 2 groups: (1) Group I was a monotherapy group consisting of 590
120
80
90
100
110
120
130
140
150mmHg
Day 0
FIGURE
2. Diastolii
blood
pressure.
patients treated with 2 tablets of Aldactazine per day; of these, 482 came back for the 2 follow-up visits (Table I). (2) Group II was a combination therapy group consisting of 329 patients who received Aldactazine (1 or 2 tablets per day) plus either a P blocker, cY-methyldopa, clonidine or another antihypertensive. Within group II, 298 patients came to the 2 follow-up visits (Table I). THE AMERICAN
JOURNAL
OF CARDIOLOGY
JUNE 19. 1990
25K
ROLE OF ALDOSTERONE
A SYMPOSlUM:
ALDOSTERONE
AND
mm Hg
Diastolic BP (mm fig)
130 120
A 60-89 I 40-59 0 20-39
110
90
595 96-104 105-119 1120 Total %
mm Hg
RGURE
115
130
3. Double
145
160
175 Day 0
190
205
220
235
product.
20-39Years
3 11 4 2 20 15.4
195 96-104 105-119 2120 Total %
40-59
Years
Aldactazine
60-89
Years
Total
%
0 2 1 0 3 5.7
4 7 3 1 15 12
3 36 25 4 68 54.40
0 3 0 0 3 6
Total
%
Dose
3 19 13 7 42 32.3
14 47 42 27 130
10.8 36.1 32.3 20.8 100
(750
mg/day)
8 7 7 7 29 54.7
9 16 17 11 53
17.0 30.2 32.1 20.8 100
+ B Blocker 1 19 17 5 42 33.60
Aldactazine 5159 160-184 185-214 2215 Total %
60-89Years Middle-Sized
+ wMethyldopa 1 7 9 4 21 39.6
Aldactazine 5159 la-184 185-214 2215 Total %
40-59Years + /3 Blocker, 8 17 25 18 68 52.3
Aldactazine
TABLE VI! Group II: Age-Related Distribution of Systolic Blood Pressure Values in Each Therapeutic Subgroup Systolic BP (mm Hg)
20-39Years AJdactazine
years years years
100 100
MEDICINE
IN CARMOVASCULAR
TABLE VIII Group II: Age-Related Distribution of Diastolic Blood Pressure Values in Each Therapeutic Subgroup
160
$ $
ANTAGONISM
8 62 45 10 125
6.4 49.60 36.00 8.00 100
%
+ wMethyldopa
0 12 7 2 21 39.6
0 13 11 5 29 54.7
Aldactazine
595 96-104 105-119 2120 Total
0 0 1 1 2 4.5
+ Clonidine 2 0 7 5 14 31.8
(450
pg/day)
3 6 12 7 28 63.6
5 6 20 13 44
11.4 13.6 45.4 29.5 100
I 0 28 18 7 53
0 52.8 34.0 13.2 100
+ Clonidine
BP = blood pressure.
Statistical evaluation: Statistical analysis was performed on the variations in systolic and diastolic BP values on day 0 and day 45 for 780 patients divided into 2 groups (monotherapy and add-on therapy). RESULTS Group
Of the initial 919 patients, 3 1 withdrew from the study because of adverse effects ( 16 from group I and 15 from group II). In addition, 107 patients were withdrawn from the study for protocol violations (Table II). TABLE
IX Percent
Change
in Blood
Pressure
at Day 45 vs Day 0 Systolic
Group I Aldact Group II B blocker o-methyldopa Clonidine Other
alone
Diastolic
BP
THE AMERICAN
JOURNAL
BP
Mean (W
Range* (X0)
No. of
Mean w
Range* W)
No. of
PtS.
14.3
13.6-15.0
482
13.4
12.7-14.1
498
15.4 16.0 16.6 12.9
12xX17.0 13.9-18.2 13.5-19.6 11.0-14.7
125 53 44 75
15.5 14.5 18 14.8
13817.2 11.2-17.6 14.4-21.6 12.7-16.8
130 53 44 76
* 95% confidence interval. Aldact = Aldactazine; BP = blood pressure.
26K
I (monothwapy): Baseline systolic BP varied between 160 and 210 mm Hg in 83% of the cases (Table III). Baseline diastolic BP ranged between 95 and 116 mm Hg in 81% of the patients (Table IV). There was a marked reduction in systolic BP between day 0 and day 45. The variations in systolic BP between day 0 and day 45, broken down by age group, are listed in Table V. The systolic BP profiles between day 0 and day 45 were parallel for the various age groups, with the lower readings, as expected, in the younger age group (Fig. 1).
OF CARDIOLOGY
VOLUME
65
PtS.
Diastolic pressure decreased greatly between day 0 and day 45 (Table VI). The statistical analysis of diastolic BP variations confirmed this decrease (Fig. 2). Diastolic BP values were not broken down into the different age groups. Statistical analysis showed that age had an effect on double product (systolic BP X heart rate) as well (Fig. 3). The best results were obtained in hypertensive patients older than 60 years. Group II (combination therapy): Tables VII and VIII show the distribution of BP values as a function of age in the 3 therapeutic subgroups (Aldactazine + /3 blocker, Aldactazine + a-methyldopa, and Aldactazine + clonidine). Both systolic and diastolic BP decreased very markedly between day 0 and day 45. Statistical analysis shows the benefits of the combination of Aldactazine and the various antihypertensive agents (B blocker, methyldopa, or clonidine) vs monotherapy with Aldactazine alone (Table IX). Although significance could not be determined because of the lack of a suitable control group, the combination of Aldactazine and clonidine was especially effective, particularly since the patients in this subgroup ‘ABLE
X
5 and
Day
Percent
Change
in Double
Product
Between
Day
0
Group I Aldact Group II fl blocker a-methyldopa Clonidine Other
alone
Mean (%)
Range* W)
No. of Pk.
17.2
16.1-18.3
488
24.1 21 .o 20.0 17.4
21.3-26.8 17.9-23.9 15.1-24.6 14.2-20.5
114 45 36 69
* (I=.% r,,r%fd~nr~ in+o.n,;.,
TABLE
XI Adverse
Effects
with
Each
Therapeutic
were older and had relatively higher BP levels than those in the other subgroups (Table IX). The statistical analysis of the double product showed that combination therapy, especially Aldactazine plus p blocker, was particularly effective, presumably because of the bradycardiac effect of the /3 blocker (Table X). ADVERSE EFFECTS A number of minor adverse effects were recorded in each group, consisting mostly of gastrointestinal disturbances and orthostatic hypotension (Table XI). One patient with gout in group I had an attack during the treatment period. CONCLUSIONS
Although the absence of a control group precluded calculations of statistical significance, the results of this large multicenter study demonstrate that a combination product of aldosterone antagonist (spironolactone) is both safe and effective in the treatment of hypertension, whether used alone or when combined with other “addon” antihypertensive agents (B blockers, methyldopa, clonidine). REFERENCES 1. Joint National Committee. The 1988 report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure. ,&C/I lnrern Med 1988:148:1023-1038. 2. Dreslinski GR, Frohlich ED, Messerli FH, Batson HM. Diuretics. fracrical Cardiology I 980,6:132m14S. 3. Hollitield JW. Thiazide treatment of hypertension: effects of thiazide diuretics on serum potassium, magnesium, and ventricular ectopy. Am J Med /986;80: suppl4A:8-12. 4. Whang R. Magnesium deficiency: pathogenesis, prevalence, and clinical implications. Am J Med 1987:72:suppl 3A:24&29. 5. Dyckner T, Wester PO. Potassium/magnesium depletion in patients with cardiovascular disease. Am J Med 1987;82:.wppl 3A:ll-17. 6. Muller J. Spironolactone in the management of congestive cardiac failure: a review. Clin Ther 1986:9x53-76.
Regimen Group II Combination Add-On (293
Group I Monotherapy (482 Patients): Aldactazine
fl Blocker
a-Methyldopa
Clonidine
GI disturbances Orthostatic hypotension Weakness Muscle cramps Headache Pollakiuria
18 16 8 4 3 2
6 7 1 3 3 -
2 1 1 -
3 2 1 1
Gynecomastia. mild Thirst K+t K+i Dry mouth Diarrhea Constipation Sleep disturbances Skin rash Visual disturbances Gout
2 1 1 1
1 -
1 1 -
1
Adverse
Effects
GI = gastrointestinal:
K+tl = potassium
1 1 1 1 increased
Therapy Patients)
-
and decreased.
THE AMERICAN
JOURNAL
OF CARDIOLOGY
JUNE
19,
1990
27K