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Alpha blockade: An overview of efficacy data
Alpha Blockade An Overview of Efficacy Data
PRISCILLA S. KINCAID-SMITH, M.D., F.R.C.P., F.R.A.C.P., D.C.P.A. Parkvile,
Australia
From the Department of Medicine, University of Melbourne, Melbourne, Australia, and the Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia. Requests for reprints should be addressed to Dr. Priscilla S. KincaidSmith, Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
The antihypertenslve effects of the alpha-adrenergic blocking agent prazosin have been studied extensively. Prazosin exerts a vasodilatory effect via selective competitive blockade of post-junctional alpha, adrenoceptors. Results of various other clinical trials suggest that the selective alpha,-adrenoceptor antagonist prazosin has a significant impact on two of the three primary coronary heart disease risk factors. In the articles reviewed herein, prazosin is shown to be an effective agent when used alone or in combination with other agents. Stamler and co-workers showed that prazosin alone achieves successful control of blood pressure equal to that of hydrochlorothiazide. lnouye et al compared the effectiveness of prazosin with propranolol and hydrochlorothiazide and found all three drugs to be comparable. Okun reveals the efficacy of prazosin across the spectrum of hypertension-mild, moderate, and severe. Additionally, Okun’s prazosin versus captopril study revealed equal efficacy between these two drugs. The long-term comparative data of Lowenstein and Neusy show prazosin and atenolol to be equally effective as monotherapy after one year. Until recently, the effects of antihypertensive therapy on the physiologic and biochemical functions that lead to the development of additional disease processes during long-term therapy had received little attention. Although the reduction of blood pressure has resulted in a significant decrease in the incidence of cerebrovascular disease among patients with hypertension, it has not been shown to protect patients from the development of coronary heart disease. It has been amply documented that hypertension, hypercholesterolemia, and cigarette smoking are risk factors for coronary heart disease. The early Framingham Study data [I ,2] stressed the significance of hypercholesterolemia as a risk factor and, more recently, studies have demonstrated that high-density lipoprotein cholesterol is also important in the genesis of coronary heart disease [3,4]. Milder forms of hypertension are now being treated, and because the risks are less in this patient group, the side effects of treatment are more significant [5,6]. Prazosin, an alpha,-adrenoceptor antagonist, has been shown to be effective in the treatment of hypertension and generally has no adverse effect on lipid profiles of patients with hypertension. _
CLINICAL PHARMACOLOGY AND EFFICACY OF PRAZOSIN Although the exact mechanism of action is unknown, it is generally believed that prazosin reduces blood pressure by decreasing peripheral vascular resistance through the selective blockade of postsynaptic (vas-
January
5, 1987
The American
Journal
of Medicine
Volume
82 (suppl
1A)
21
SYMPOSIUM
TABLE
ON ALPHA BLOCKADE-KINCAID-SMITH
I
Effects of Hydrochlorothiazide, Patients with Hypertension
Propranolol,
and Prazosin
Sitting Systolic Blood Pressure (mm W Baseline (n = 13) Hydrochlorothiazide (n = 13) Propranolol (n = 12) Prazosin (n = 13)
on Systolic
Blood
Pressure
Standing Heart Rate (beats/minute)
Systolic Blood Pressure (mm H!f)
and Heart Rate in Supine
Heart Rate (beats/minute)
Systolic Blood Pressure (mm MU
Heart Rate (beats/minute)
153 f 16
76k
11
153 ‘- 15
80 f 12
153 2 14
68i
130 k 14’
74+
11
130 t 14t
80+
12
132 ? 12t
67211
135 2 15t
59 k 7’
137 i 17
62 ‘- Q*
135 k 157
56 k 5$
138 + 15f
75 ? 8
133 2 155
82 + 12
144 k 19
652
Adapted with permission from [8]. ‘p ~0.001 versus baseline. tp ~0.01 versus baseline. *p ~0.001 versus baseline, prazosin, §p ~0.05 versus baseline.
11
10
and hydrochlorothiazide.
receptors [7]. This selectivity allows prazosin to block the contractile response of vascular smooth muscle to norepinephrine without interfering with the activity of norepinephrine at presynaptic alpha2 sites. Prazosin. The blood pressure lowering effect of prazosin has been extensively studied. lnouye et al [8] conducted a randomized crossover study involving 14 volunteers with mild to moderate hypertension who received titrated doses of hydrochlorothiazide, propranolol, and prazosin. Patients were administered each drug for a two-month period, with a two-week washout between treatments. Heart rate was decreased significantly by propranolol, but was unaffected by hydrochlorothiazide and prazosin. The effects on blood pressure are illustrated in Table I, which shows that prazosin monotherapy produced antihypertensive effects that were comparable with those of both hydrochlorothiazide and propranolol monotherapy. Blood pressure was controlled in nine of the 13 patients treated with prazosin: sitting systolic blood pressure was reduced cular) alpha,-adrenergic
from 153 mm Hg to 138 mm Hg and sitting diastolic blood pressure was reduced from 102 mm Hg to 89 mm Hg; standing systolic and diastolic blood pressures were similarly reduced. These findings indicate that prazosin was well tolerated by all patients in doses of 1 to 10 mg twice daily. Scharf and colleagues [9] evaluated 10 patients with essential hypertension who had no end-organ damage. The dosage of prazosin was titrated from 1 mg per day up to a maximum of 20 mg per day or until diastolic blood pressure was reduced to 90 mm Hg or lower. Blood pressure was significantly reduced in all patients (Figure 1); ,sitting, standing, and supine systolic/diastolic pressures were reduced from baseline levels by 10/6 mm Hg, 12/6 mm Hg, and 14/8 mm Hg, respectively. Thus, there was little postural effect. There were no significant changes in peripheral plasma renin activity, serum aldosterone levels, or urinary sodium excretion (Table II). Cardiac ejection fraction also did not change significantly after prazo-
160 150 140 130 120 110 100
Systolic BP before treatment Systolic BP after prazosin DiasWc BP before treatment
Qo &I 70 60 50 40
D&etdii BP after or&n
Supine
22
January
5, 1987
The American
Sitting
Journal
Figure 1. Supine, sitting, and standing blood pressures during pretreatment period and after prazosin therapy. All changes from pretreatment are significant. Adapted with permission from 191.
Standing
of Medicine
Volume
82 (suppl
1 A)
SYMPOSIUM
TABLE
sin therapy. The mean dose of prazosin at eight weeks was 12.9 + 3.5 mg daily (range, 6 to 15 mg daily) and was well tolerated by all patients. No clinically detectable short-term abnormalities of cardiac function were observed. Stamler and co-workers [IO] designed a two-center, randomized trial to evaluate and compare the effects of initial antihypertensive therapy with prazosin and hydrochlorothiazide. An interim analysis presented data on 62 patients who had completed at least three months of treatment. Mean diastolic blood pressure (97 mm Hg at baseline) was reduced by 10.3 mm Hg in the prazosin group and 8.6 mm Hg in the hydrochlorothiazide group. Although prazosin and hydrochlorothiazide produced similar reductions in blood pressure, their effects on lipid levels were significantly different (Figure 2); serum total cholesterol and triglyceride levels declined in patients receiving prazosin (-4.2 ‘-’ 4.5 mg/dl and -24.0 i 10.2 mg/dl, respectively) and increased in the patients treated with hydrochlorothiazide (+8.2 ? 4.3 mg/dl and + 17.2 ? 7.8 mgidl, respectively). A study by Lowenstein and Neusy [ll] assessed the efficacy of prazosin and atenolol over the long term in patients with mild to moderate hypertension. During prazosin administration, both systolic and diastolic blood pressures were significantly lowered from baseline (156.8198.0 mm Hg) at three months (n = 21) by 13.6 mm Hg (p ~0.01) and 7.7 mm Hg (p <0.05), respectively. The antihypertensive effects of prazosin persisted after 12 months of monotherapy (n = 14) when systolic pressure was 20.4 mm Hg (p ~0.01) lower than baseline and diastolic pressure was reduced 11.9 mm Hg (p ~0.01). After three months, the 24 atenolol-treated patients showed reductions from baseline (141.8/97.7) of 9.1 mm Hg systolic (not significant) and 10.7 mm Hg diastolic (p CO.01). One year of
II
ON ALPHA BLOCKADE-KINCAID-SMITH
Effect of Prazosin on Plasma Renin Activity, Serum Aldosterone Levels, and Urinary Sodium Excretion after Eight Weeks of Continuous Therapy
Plasma renin concentration (ng/lOO ml/hour) Serum aldosterone (PgW Urinary sodium excretion (meq/24 hours) Adapted
with permission
Pretreatment (mean f SD)
After Treatment (mean k SD)
61.7 k 28.5
88.1 t 34.5
150.0
-t 34.8
151.3
152.0 2 29.0 from
+ 25.1
148.0 t 34.0
[9].
atenolol data (n = 16) showed reductions of 16.4 mm Hg systolic (p ~0.05) and 12.2 mm Hg diastolic (p ~0.01) from baseline (Figure 3). Okun [I 21 reviewed the clinical trials that initially investigated the antihypertensive effects of prazosin (Table Ill). Data from these studies supported the role of prazosin as an antihypertensive agent in the treatment of patients with mild, moderate, or severe hypertension. Prazosin was shown to be effective and to lack significant side effects in patients whose condition was complicated by other physiologic abnormalities, such as impaired renal function, hemodialysis, concomitant heart block, bronchospasm, diabetes mellitus, disturbed carbohydrate metabolism, hyperlipidemia, or hyperuricemia. In a recent study, Okun compared the antihypertensive effects of prazosin and captopril. Both drugs produced statistically significant and equal reductions in blood pressure in responding patients. The results of that study are detailed in this supplement. Lipid Metabolism. Some antihypertensive agents, including thiazide diuretics and some beta blockers, have
353025 2015
-
-20 -25 -30
-
+17.2 -c ::y: .:...: -::...j ::... . .. . . .
+8.2
-
Mean Change from Baseline OwW
Figure 2. Mean changes from baseline in total cholesterol and total triglyceride levels (mgldl) in hypertensive patients who received hydrochlorothiazide or prazosin for at least three months (prazosin n = 30; hydrochlorothiazide grow, group, n = 30). Adapted with permission from [lo].
Prazosin
Hydrochlorothiezide Total Chdesteml (mean *SE)
January
5, 1987
The
American
Journal
Prezosin
Hydrachlorothiszide Total Triglycerides (mean *SE)
of Medicine
Volume
82 (suppl
1A)
23
SYMPOSIUM
ON ALPHA BLOCKADE-KINCAID-SMITH
Prazosin
5::.;~
h
h
h
E::
3 Months (n=21)
12 Months (n= 14)
3 Months (n = 28)
12 Months (n= 17)
Atenolol
Baseline
(n = 25)
TABLE III
Studies
Figure 3. Changes in blood pressure in hypertensive patients who received either prazosin or atenolol for up to one year. Adapted with permission from [l 11.
the Efficacy of Prazosin as Monotherapy for Hypertension
Supporting
Supine Blood Pressure (mm Ho)
Study
hi)
Net Reduction in Blood Pressure fmm Baseline’
Ha&r and Delmez (1979)+ Kincaid-Smith (1977) O’Connor et al (1979) Letcher et al (1979) Mulvihill-Wilson et al (1979) Turner et al (1977) Smith et al (1975) New drug application data
16 15 5.0 10 NA
30125 52134 21123 20113 I 518
6.8
25118
Mean Daily Dose of Prazosin
NA = not available. Adapted with permission from [I 21. *All reductions in blood pressure from ‘Patients receiving dialysis
baseline
NA NA
are statistically
13 (diastolic) 15113
SIDE EFFECTS In general, the side effects of prazosin are mild, transient, and few in number. Those that are most often observeddizziness, vertigo, weakness, and headache-are consequences of the pharmacologic action of this agent on the cardiovascular postural reflexes and rarely require discontinuation of treatment. In more than 10 years of usage,
January
5, 1987
The American
Journal
of Medicine
154177 142164 I 35185
I 58194
142191 141189 121 I 53189
significant.
been shown to unfavorably affect the blood lipid profile in patients with hypertension, but this effect is generally not seen with postsynaptic alpha blocking agents. In light of increased awareness of the importance of hypercholesterolemia as a risk factor for coronary heart disease, changes in blood lipids induced by antihypettensive drugs cannot be ignored when conducting hypertension trials. The lipid changes induced by antihypertensive agents are discussed in Leren’s article (elsewhere in this supplement).
24
Blood Pressure after Prazosln Therapy
Volume
tolerance to prazosin ment of hypertension.
has not been reported
in the treat-
COMMENTS Prazosin has long been recognized as an effective antihypertensive agent. The studies highlighted in this article suggest that prazosin generally has no adverse effects on the lipid profile in terms of atherogenic lipids. Since prazosin produces blood pressure control equal to that of both beta blockers and thiazides, without their attendant lipid effects, it is an agent extremely well suited to monotherapy for the treatment of hypertension over the long term. If other drugs are needed, prazosin adds to their effectiveness. Improving total cardiovascular health, not just lowering blood pressure, should be a goal of antihypertensive therapy. The apparent ability of prazosin to tolerably impact on total coronary heart disease risk makes it an ideal therapy for treating hypertension.
82 (suppl
1A)
SYMPOSIUM
ON ALPHA BLOCKADE-KINCAID-SMITH
REFERENCES 1.
2.
3.
4.
5. 6.
7.
Kannel WB, McGee D, Gordon T: A general cardiovascular risk profile: The Framingham Study. Am J Cardiol 1976; 36: 4651. Gordon T, Castelli WP, Hjortland MC, et al: High-density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977; 62: 707-713. Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1964; 251: 351-364. Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984; 251: 365-374. Freis ED: Should mild hypertension be treated? N Engl J Med 1982; 307: 306-309. Results of the Hypertension Detection and Follow-up Program. The effect of treatment on mortality in “mild” hypertension. N Engl J Med 1982; 307: 976-980. Stanaszek WF, Kellerman D, Brogden RN, Romankiewicz JA:
January
5, 1987
6.
9.
10.
11.
12.
The
Prazosin update: a review of its pharmacological properties and therapeutic use in hypertension and congestive heart failure. Drugs 1963; 25: 339-364. lnouye I, Massie B, Benowitz N, Simpson P, Loge D, Topic N: Monotherapy in mild to moderate hypertension: comparison of hydrochlorothiazide, propranolol and prazosin. Am J Cardiol 1964; 53: 24A-26A. Scharf SC, Lee H-B, Wexler JP, Blaufox MD: Cardiovascular consequences of primary antihypertensive therapy with prazosin hydrochloride. Am J Cardiol 1984. 53: 32A-36A. Stamler R, Stamler J, Gosch FC, Berkson DM, Dyer A, Hershinow P: Initial antihypertensive drug therapy: alpha blocker or diuretic. Interim report of a randomized trial. Am J Med 1986; 80 (suppl 2A): 90-93. Neusy A-J, Lowenstein J: Effects of prazosin, atenolol, and thiazide diuretic on plasma lipids in patients with essential hypertension. Am J Med 1986; 80 (suppl 2A): 94-99. Okun R: Effectiveness of prazosin as initial antihypertensive therapy. Am J Cardiol 1983; 51: 644-650.
American
Journal
of Medicine
Volume
82 (suppl
1A)
25
PRISCILLA S. KINCAID-SMITH, M.D., F.R.C.P., F.R.A.C.P., D.C.P.A. Parkvile,
Australia
From the Department of Medicine, University of Melbourne, Melbourne, Australia, and the Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia. Requests for reprints should be addressed to Dr. Priscilla S. KincaidSmith, Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
The antihypertenslve effects of the alpha-adrenergic blocking agent prazosin have been studied extensively. Prazosin exerts a vasodilatory effect via selective competitive blockade of post-junctional alpha, adrenoceptors. Results of various other clinical trials suggest that the selective alpha,-adrenoceptor antagonist prazosin has a significant impact on two of the three primary coronary heart disease risk factors. In the articles reviewed herein, prazosin is shown to be an effective agent when used alone or in combination with other agents. Stamler and co-workers showed that prazosin alone achieves successful control of blood pressure equal to that of hydrochlorothiazide. lnouye et al compared the effectiveness of prazosin with propranolol and hydrochlorothiazide and found all three drugs to be comparable. Okun reveals the efficacy of prazosin across the spectrum of hypertension-mild, moderate, and severe. Additionally, Okun’s prazosin versus captopril study revealed equal efficacy between these two drugs. The long-term comparative data of Lowenstein and Neusy show prazosin and atenolol to be equally effective as monotherapy after one year. Until recently, the effects of antihypertensive therapy on the physiologic and biochemical functions that lead to the development of additional disease processes during long-term therapy had received little attention. Although the reduction of blood pressure has resulted in a significant decrease in the incidence of cerebrovascular disease among patients with hypertension, it has not been shown to protect patients from the development of coronary heart disease. It has been amply documented that hypertension, hypercholesterolemia, and cigarette smoking are risk factors for coronary heart disease. The early Framingham Study data [I ,2] stressed the significance of hypercholesterolemia as a risk factor and, more recently, studies have demonstrated that high-density lipoprotein cholesterol is also important in the genesis of coronary heart disease [3,4]. Milder forms of hypertension are now being treated, and because the risks are less in this patient group, the side effects of treatment are more significant [5,6]. Prazosin, an alpha,-adrenoceptor antagonist, has been shown to be effective in the treatment of hypertension and generally has no adverse effect on lipid profiles of patients with hypertension. _
CLINICAL PHARMACOLOGY AND EFFICACY OF PRAZOSIN Although the exact mechanism of action is unknown, it is generally believed that prazosin reduces blood pressure by decreasing peripheral vascular resistance through the selective blockade of postsynaptic (vas-
January
5, 1987
The American
Journal
of Medicine
Volume
82 (suppl
1A)
21
SYMPOSIUM
TABLE
ON ALPHA BLOCKADE-KINCAID-SMITH
I
Effects of Hydrochlorothiazide, Patients with Hypertension
Propranolol,
and Prazosin
Sitting Systolic Blood Pressure (mm W Baseline (n = 13) Hydrochlorothiazide (n = 13) Propranolol (n = 12) Prazosin (n = 13)
on Systolic
Blood
Pressure
Standing Heart Rate (beats/minute)
Systolic Blood Pressure (mm H!f)
and Heart Rate in Supine
Heart Rate (beats/minute)
Systolic Blood Pressure (mm MU
Heart Rate (beats/minute)
153 f 16
76k
11
153 ‘- 15
80 f 12
153 2 14
68i
130 k 14’
74+
11
130 t 14t
80+
12
132 ? 12t
67211
135 2 15t
59 k 7’
137 i 17
62 ‘- Q*
135 k 157
56 k 5$
138 + 15f
75 ? 8
133 2 155
82 + 12
144 k 19
652
Adapted with permission from [8]. ‘p ~0.001 versus baseline. tp ~0.01 versus baseline. *p ~0.001 versus baseline, prazosin, §p ~0.05 versus baseline.
11
10
and hydrochlorothiazide.
receptors [7]. This selectivity allows prazosin to block the contractile response of vascular smooth muscle to norepinephrine without interfering with the activity of norepinephrine at presynaptic alpha2 sites. Prazosin. The blood pressure lowering effect of prazosin has been extensively studied. lnouye et al [8] conducted a randomized crossover study involving 14 volunteers with mild to moderate hypertension who received titrated doses of hydrochlorothiazide, propranolol, and prazosin. Patients were administered each drug for a two-month period, with a two-week washout between treatments. Heart rate was decreased significantly by propranolol, but was unaffected by hydrochlorothiazide and prazosin. The effects on blood pressure are illustrated in Table I, which shows that prazosin monotherapy produced antihypertensive effects that were comparable with those of both hydrochlorothiazide and propranolol monotherapy. Blood pressure was controlled in nine of the 13 patients treated with prazosin: sitting systolic blood pressure was reduced cular) alpha,-adrenergic
from 153 mm Hg to 138 mm Hg and sitting diastolic blood pressure was reduced from 102 mm Hg to 89 mm Hg; standing systolic and diastolic blood pressures were similarly reduced. These findings indicate that prazosin was well tolerated by all patients in doses of 1 to 10 mg twice daily. Scharf and colleagues [9] evaluated 10 patients with essential hypertension who had no end-organ damage. The dosage of prazosin was titrated from 1 mg per day up to a maximum of 20 mg per day or until diastolic blood pressure was reduced to 90 mm Hg or lower. Blood pressure was significantly reduced in all patients (Figure 1); ,sitting, standing, and supine systolic/diastolic pressures were reduced from baseline levels by 10/6 mm Hg, 12/6 mm Hg, and 14/8 mm Hg, respectively. Thus, there was little postural effect. There were no significant changes in peripheral plasma renin activity, serum aldosterone levels, or urinary sodium excretion (Table II). Cardiac ejection fraction also did not change significantly after prazo-
160 150 140 130 120 110 100
Systolic BP before treatment Systolic BP after prazosin DiasWc BP before treatment
Qo &I 70 60 50 40
D&etdii BP after or&n
Supine
22
January
5, 1987
The American
Sitting
Journal
Figure 1. Supine, sitting, and standing blood pressures during pretreatment period and after prazosin therapy. All changes from pretreatment are significant. Adapted with permission from 191.
Standing
of Medicine
Volume
82 (suppl
1 A)
SYMPOSIUM
TABLE
sin therapy. The mean dose of prazosin at eight weeks was 12.9 + 3.5 mg daily (range, 6 to 15 mg daily) and was well tolerated by all patients. No clinically detectable short-term abnormalities of cardiac function were observed. Stamler and co-workers [IO] designed a two-center, randomized trial to evaluate and compare the effects of initial antihypertensive therapy with prazosin and hydrochlorothiazide. An interim analysis presented data on 62 patients who had completed at least three months of treatment. Mean diastolic blood pressure (97 mm Hg at baseline) was reduced by 10.3 mm Hg in the prazosin group and 8.6 mm Hg in the hydrochlorothiazide group. Although prazosin and hydrochlorothiazide produced similar reductions in blood pressure, their effects on lipid levels were significantly different (Figure 2); serum total cholesterol and triglyceride levels declined in patients receiving prazosin (-4.2 ‘-’ 4.5 mg/dl and -24.0 i 10.2 mg/dl, respectively) and increased in the patients treated with hydrochlorothiazide (+8.2 ? 4.3 mg/dl and + 17.2 ? 7.8 mgidl, respectively). A study by Lowenstein and Neusy [ll] assessed the efficacy of prazosin and atenolol over the long term in patients with mild to moderate hypertension. During prazosin administration, both systolic and diastolic blood pressures were significantly lowered from baseline (156.8198.0 mm Hg) at three months (n = 21) by 13.6 mm Hg (p ~0.01) and 7.7 mm Hg (p <0.05), respectively. The antihypertensive effects of prazosin persisted after 12 months of monotherapy (n = 14) when systolic pressure was 20.4 mm Hg (p ~0.01) lower than baseline and diastolic pressure was reduced 11.9 mm Hg (p ~0.01). After three months, the 24 atenolol-treated patients showed reductions from baseline (141.8/97.7) of 9.1 mm Hg systolic (not significant) and 10.7 mm Hg diastolic (p CO.01). One year of
II
ON ALPHA BLOCKADE-KINCAID-SMITH
Effect of Prazosin on Plasma Renin Activity, Serum Aldosterone Levels, and Urinary Sodium Excretion after Eight Weeks of Continuous Therapy
Plasma renin concentration (ng/lOO ml/hour) Serum aldosterone (PgW Urinary sodium excretion (meq/24 hours) Adapted
with permission
Pretreatment (mean f SD)
After Treatment (mean k SD)
61.7 k 28.5
88.1 t 34.5
150.0
-t 34.8
151.3
152.0 2 29.0 from
+ 25.1
148.0 t 34.0
[9].
atenolol data (n = 16) showed reductions of 16.4 mm Hg systolic (p ~0.05) and 12.2 mm Hg diastolic (p ~0.01) from baseline (Figure 3). Okun [I 21 reviewed the clinical trials that initially investigated the antihypertensive effects of prazosin (Table Ill). Data from these studies supported the role of prazosin as an antihypertensive agent in the treatment of patients with mild, moderate, or severe hypertension. Prazosin was shown to be effective and to lack significant side effects in patients whose condition was complicated by other physiologic abnormalities, such as impaired renal function, hemodialysis, concomitant heart block, bronchospasm, diabetes mellitus, disturbed carbohydrate metabolism, hyperlipidemia, or hyperuricemia. In a recent study, Okun compared the antihypertensive effects of prazosin and captopril. Both drugs produced statistically significant and equal reductions in blood pressure in responding patients. The results of that study are detailed in this supplement. Lipid Metabolism. Some antihypertensive agents, including thiazide diuretics and some beta blockers, have
353025 2015
-
-20 -25 -30
-
+17.2 -c ::y: .:...: -::...j ::... . .. . . .
+8.2
-
Mean Change from Baseline OwW
Figure 2. Mean changes from baseline in total cholesterol and total triglyceride levels (mgldl) in hypertensive patients who received hydrochlorothiazide or prazosin for at least three months (prazosin n = 30; hydrochlorothiazide grow, group, n = 30). Adapted with permission from [lo].
Prazosin
Hydrochlorothiezide Total Chdesteml (mean *SE)
January
5, 1987
The
American
Journal
Prezosin
Hydrachlorothiszide Total Triglycerides (mean *SE)
of Medicine
Volume
82 (suppl
1A)
23
SYMPOSIUM
ON ALPHA BLOCKADE-KINCAID-SMITH
Prazosin
5::.;~
h
h
h
E::
3 Months (n=21)
12 Months (n= 14)
3 Months (n = 28)
12 Months (n= 17)
Atenolol
Baseline
(n = 25)
TABLE III
Studies
Figure 3. Changes in blood pressure in hypertensive patients who received either prazosin or atenolol for up to one year. Adapted with permission from [l 11.
the Efficacy of Prazosin as Monotherapy for Hypertension
Supporting
Supine Blood Pressure (mm Ho)
Study
hi)
Net Reduction in Blood Pressure fmm Baseline’
Ha&r and Delmez (1979)+ Kincaid-Smith (1977) O’Connor et al (1979) Letcher et al (1979) Mulvihill-Wilson et al (1979) Turner et al (1977) Smith et al (1975) New drug application data
16 15 5.0 10 NA
30125 52134 21123 20113 I 518
6.8
25118
Mean Daily Dose of Prazosin
NA = not available. Adapted with permission from [I 21. *All reductions in blood pressure from ‘Patients receiving dialysis
baseline
NA NA
are statistically
13 (diastolic) 15113
SIDE EFFECTS In general, the side effects of prazosin are mild, transient, and few in number. Those that are most often observeddizziness, vertigo, weakness, and headache-are consequences of the pharmacologic action of this agent on the cardiovascular postural reflexes and rarely require discontinuation of treatment. In more than 10 years of usage,
January
5, 1987
The American
Journal
of Medicine
154177 142164 I 35185
I 58194
142191 141189 121 I 53189
significant.
been shown to unfavorably affect the blood lipid profile in patients with hypertension, but this effect is generally not seen with postsynaptic alpha blocking agents. In light of increased awareness of the importance of hypercholesterolemia as a risk factor for coronary heart disease, changes in blood lipids induced by antihypettensive drugs cannot be ignored when conducting hypertension trials. The lipid changes induced by antihypertensive agents are discussed in Leren’s article (elsewhere in this supplement).
24
Blood Pressure after Prazosln Therapy
Volume
tolerance to prazosin ment of hypertension.
has not been reported
in the treat-
COMMENTS Prazosin has long been recognized as an effective antihypertensive agent. The studies highlighted in this article suggest that prazosin generally has no adverse effects on the lipid profile in terms of atherogenic lipids. Since prazosin produces blood pressure control equal to that of both beta blockers and thiazides, without their attendant lipid effects, it is an agent extremely well suited to monotherapy for the treatment of hypertension over the long term. If other drugs are needed, prazosin adds to their effectiveness. Improving total cardiovascular health, not just lowering blood pressure, should be a goal of antihypertensive therapy. The apparent ability of prazosin to tolerably impact on total coronary heart disease risk makes it an ideal therapy for treating hypertension.
82 (suppl
1A)
SYMPOSIUM
ON ALPHA BLOCKADE-KINCAID-SMITH
REFERENCES 1.
2.
3.
4.
5. 6.
7.
Kannel WB, McGee D, Gordon T: A general cardiovascular risk profile: The Framingham Study. Am J Cardiol 1976; 36: 4651. Gordon T, Castelli WP, Hjortland MC, et al: High-density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977; 62: 707-713. Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1964; 251: 351-364. Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984; 251: 365-374. Freis ED: Should mild hypertension be treated? N Engl J Med 1982; 307: 306-309. Results of the Hypertension Detection and Follow-up Program. The effect of treatment on mortality in “mild” hypertension. N Engl J Med 1982; 307: 976-980. Stanaszek WF, Kellerman D, Brogden RN, Romankiewicz JA:
January
5, 1987
6.
9.
10.
11.
12.
The
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American
Journal
of Medicine
Volume
82 (suppl
1A)
25