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Summary of prazosin lipid studies
Summary of Prazosin Lipid Studies Albert0 Zanchetti. M.D.
In addition to reviewing current knowledge on hypertension as one of the risk factors for coronary heart disease, a primary objective of this symposium was to evaluate the effects that correction of one risk factor, hypertension, may exert on other risk factors, such as blood lipids. Eight original contributions were presented regarding the effect on blood lipids of antihypettensive treatment with prazosin alone, or in combination with other antihypertensive agents. The effects of prazosin have also been compared with those of beta blockers. These data are summarized in Table I. Prazosin was administered as the only antihypertensive agent for periods ranging from eight weeks to one year in four studies [l-4]. Total cholesterol was not affected or significantly decreased; high-density lipoprotein cholesterol did not change or was significantly increased; and the highdensity lipoprotein:total cholesterol ratio was consistently increased, significantly in three studies [1,2,4]. In two of these four studies, comparison was made between the effects of prazosin and those of beta blockers [ 1,2]. The beta blockers did not consistently influence total cholesterol, but in both studies administration of a beta blocker significantly lowered highdensity lipoprotein cholesterol and consequently significantly reduced the highdensity lipoprotein:total cholesterol ratio. In these two studies triglycerides were also significantly reduced by prazosin and significantly increased by beta blockers. The effects of either prazosin or a beta blocker added to preceding diuretic therapy were investigated in three studies [5-71. With patients receiving added prazosin, total cholesterol did not change or was significantly decreased. High-density lipoprotein cholesterol showed a consistent trend towards higher values in all studies, and in one study the increase was significant [6]. The
high-density lipoprotein:total cholesterol ratio was raised significantly in two studies [5,6]; triglycerides were reduced in all studies, significantly in two studies [5,6]. The beta blocker, propranolol, did not appear to influence total cholesterol, but slightly reduced highdensity lipoprotein cholesterol and the high-density lipoprotein:total cholesterol ratio (significantly in one study only) [7]; triglycerides were increased by propranolol in two of the three studies, significantly in one study [7]. The addition of prazosin to a beta blocker/diuretic combination was tested by Mauersberger [a]. Total cholesterol was unaffected, and high-density lipoprotein cholesterol and the high-density lipoprotein: total cholesterol ratio was significantly increased. Triglycerides and very low-density lipoprotein cholesterol were also unchanged. It appears, therefore, that prazosin, while effectively lowering blood pressure in hypertensive patients, consistently and favorably affects blood lipids when it is administered alone. When prazosin is combined with diuretic or beta blocking agents it is also capable of correcting some of the alterations induced by these drugs. Far-reaching conclusions are as yet unwarranted. Indeed, the changes in blood lipids induced by antihypertensive drugs are small, and have seldom been followed for more than one year. Their impact on development of cardiovascular disease can only be surmised. However, faced as we are with a substantial failure or a very limited success in preventing coronary heart disease by antihypertensive therapy, we must urgently test the hypothesis that more successful antihypertensive therapy might be obtained by a more rational use of antihypertensive agents.
from the Center for Clinical Physiology and Hypertension, University of Milan, Ospedale Maggiore, Milan, /ta/y. Reprint requests should be addressed to Professor A. Zancheiti, Centro di Fisiologia Clinica e Ipertensione, University of Milan, Ospedale Maggiore, Via F. Sforza 35, 20 122 Milan, Italy.
122
February 27, 1994
The American Journal of Medicine
+1 -1
+14***
-1
-
+1
-20”’
-6”
-
l
-1
22 8
+10*
-2,‘“”
-1
-4 (LDL and VLDL) -
+4
34 12
-3
+17
+1
-
+2
-2
26 12
+5
-6
+2
-12
+5
+4
20 12
-10’
+23’
+1
+31*
NC
-10’
20 12
+13*
-3
-2
-3
-5
+11*
15 8
+35”*
-,O’”
-8”’
-19”
-13’“’
+13***
24 12
-16”’
+,8”‘”
+3”
+20*
+6’
-10’
26 12
-13”‘”
23 8
+7”
-16”’
-9”“”
-15””
+24***
-1
-10”’ +2 (LDL and (LDL and VLDL) VLDL) -
-4
23 8
+5
+7
+3
-
-
+9*
15 12
+19*
-7
+2
-
l-17”
15 52
Takabatake Rouffyand Katberand Sauberlich[3]* $rtJAc Jaillard[ 114 Leren[2p Prazosin Atenelol PrazosinPropranolol Prarosin
l
l
’ Prazosin or propranolol added to diuretic (polythiazide). 2 Prazosin or propranolol added to trichloromethiazide or other diuretic. 3 Prazosin added to fixed combination of oxprenolol and chlorthalidone. 4 Prazosin or atenolol administered as single agent. 5 Prazosin or propranolol administered as single agent. 6 Prazosin administered as single agent. LDL = low-density lipoprotein cholesterol: VLDL = very low-density lipoprotein cholesterol Percentage changes are given to the nearest whole number. * p <0.05; * p
(Percent change) Triglycerides (Percent change) Cholesterol ratio (Percent change)
lipoprotein (Percent change) Total cholesterol
Very low-density
(weeks) High-density lipoprotein +8’ (Percent change) Low-density lipoprotein - 10’ (Percent change)
25 8
Lowenslein Johnsen and Neusy[5]’ Goto[6p et al [?]I Yauwsberger]6p Prazosin Propranolol Prazesin Propranolol Prazosin Propranolol Prazesin
Summary of Prazosin Lipid Studies
Number of patients Duration of study
TABLE I
REFERENCES 1.
2. 3.
4.
5.
124
Rouffy J. Jaillard J: Comparative effects of prazosin and atenofol on plasma lipids in hypertensive patients. Am J Med 1984; 76 (suppl 2A): 105-108. Leren P: Effect of alpha- and beta-blocker therapy on blood lipids. Am J Med 1984; 76 (suppl 2A): 67-7 1. Kather Ii, Sauberlich P: Comparison of in vitro and in vivo effects of prazosin on lipid metabolism. Am J Med 1984; 76 (suppl 2A): 89-93. Takabatake T, Ohta M, Maekawa M, et al: Effects of long-term prazosin therapy on lipoprotein metabolism in hypertensive patients. Am J Med 1984; 76 (suppl 2A): 113-l 16. Lowenstein J, Neusy A-J: Effects of prazosin and propranolol
February
27, 1984
The American
Journal of Medicine
6.
7.
8.
on serum lipids in patients with essential hypertension. Am J Med 1984; 76 (suppl2A): 79-84. Goto Y: Effects of alpha- and beta-blocker antihypertensive therapy on blood lipids: a multicenter trial. Am J Med 1984; 76 (suppl 2A): 72-78. Johnson BF. Romero L. Johnson J, Marwaha R: Comparative effects of propranolol and prazosin upon serum lipids in thiazide-treated hypertensive patients. Am J Med 1984; 76 (suppl2A): 109- 112. Mauersberger H: Effect of prazosin on blood pressure and plasma lipids in patients receiving a beta-blocker and diuretic regimen. Am J Med 1984; 76 (suppl2A): 101-104.
In addition to reviewing current knowledge on hypertension as one of the risk factors for coronary heart disease, a primary objective of this symposium was to evaluate the effects that correction of one risk factor, hypertension, may exert on other risk factors, such as blood lipids. Eight original contributions were presented regarding the effect on blood lipids of antihypettensive treatment with prazosin alone, or in combination with other antihypertensive agents. The effects of prazosin have also been compared with those of beta blockers. These data are summarized in Table I. Prazosin was administered as the only antihypertensive agent for periods ranging from eight weeks to one year in four studies [l-4]. Total cholesterol was not affected or significantly decreased; high-density lipoprotein cholesterol did not change or was significantly increased; and the highdensity lipoprotein:total cholesterol ratio was consistently increased, significantly in three studies [1,2,4]. In two of these four studies, comparison was made between the effects of prazosin and those of beta blockers [ 1,2]. The beta blockers did not consistently influence total cholesterol, but in both studies administration of a beta blocker significantly lowered highdensity lipoprotein cholesterol and consequently significantly reduced the highdensity lipoprotein:total cholesterol ratio. In these two studies triglycerides were also significantly reduced by prazosin and significantly increased by beta blockers. The effects of either prazosin or a beta blocker added to preceding diuretic therapy were investigated in three studies [5-71. With patients receiving added prazosin, total cholesterol did not change or was significantly decreased. High-density lipoprotein cholesterol showed a consistent trend towards higher values in all studies, and in one study the increase was significant [6]. The
high-density lipoprotein:total cholesterol ratio was raised significantly in two studies [5,6]; triglycerides were reduced in all studies, significantly in two studies [5,6]. The beta blocker, propranolol, did not appear to influence total cholesterol, but slightly reduced highdensity lipoprotein cholesterol and the high-density lipoprotein:total cholesterol ratio (significantly in one study only) [7]; triglycerides were increased by propranolol in two of the three studies, significantly in one study [7]. The addition of prazosin to a beta blocker/diuretic combination was tested by Mauersberger [a]. Total cholesterol was unaffected, and high-density lipoprotein cholesterol and the high-density lipoprotein: total cholesterol ratio was significantly increased. Triglycerides and very low-density lipoprotein cholesterol were also unchanged. It appears, therefore, that prazosin, while effectively lowering blood pressure in hypertensive patients, consistently and favorably affects blood lipids when it is administered alone. When prazosin is combined with diuretic or beta blocking agents it is also capable of correcting some of the alterations induced by these drugs. Far-reaching conclusions are as yet unwarranted. Indeed, the changes in blood lipids induced by antihypertensive drugs are small, and have seldom been followed for more than one year. Their impact on development of cardiovascular disease can only be surmised. However, faced as we are with a substantial failure or a very limited success in preventing coronary heart disease by antihypertensive therapy, we must urgently test the hypothesis that more successful antihypertensive therapy might be obtained by a more rational use of antihypertensive agents.
from the Center for Clinical Physiology and Hypertension, University of Milan, Ospedale Maggiore, Milan, /ta/y. Reprint requests should be addressed to Professor A. Zancheiti, Centro di Fisiologia Clinica e Ipertensione, University of Milan, Ospedale Maggiore, Via F. Sforza 35, 20 122 Milan, Italy.
122
February 27, 1994
The American Journal of Medicine
+1 -1
+14***
-1
-
+1
-20”’
-6”
-
l
-1
22 8
+10*
-2,‘“”
-1
-4 (LDL and VLDL) -
+4
34 12
-3
+17
+1
-
+2
-2
26 12
+5
-6
+2
-12
+5
+4
20 12
-10’
+23’
+1
+31*
NC
-10’
20 12
+13*
-3
-2
-3
-5
+11*
15 8
+35”*
-,O’”
-8”’
-19”
-13’“’
+13***
24 12
-16”’
+,8”‘”
+3”
+20*
+6’
-10’
26 12
-13”‘”
23 8
+7”
-16”’
-9”“”
-15””
+24***
-1
-10”’ +2 (LDL and (LDL and VLDL) VLDL) -
-4
23 8
+5
+7
+3
-
-
+9*
15 12
+19*
-7
+2
-
l-17”
15 52
Takabatake Rouffyand Katberand Sauberlich[3]* $rtJAc Jaillard[ 114 Leren[2p Prazosin Atenelol PrazosinPropranolol Prarosin
l
l
’ Prazosin or propranolol added to diuretic (polythiazide). 2 Prazosin or propranolol added to trichloromethiazide or other diuretic. 3 Prazosin added to fixed combination of oxprenolol and chlorthalidone. 4 Prazosin or atenolol administered as single agent. 5 Prazosin or propranolol administered as single agent. 6 Prazosin administered as single agent. LDL = low-density lipoprotein cholesterol: VLDL = very low-density lipoprotein cholesterol Percentage changes are given to the nearest whole number. * p <0.05; * p
(Percent change) Triglycerides (Percent change) Cholesterol ratio (Percent change)
lipoprotein (Percent change) Total cholesterol
Very low-density
(weeks) High-density lipoprotein +8’ (Percent change) Low-density lipoprotein - 10’ (Percent change)
25 8
Lowenslein Johnsen and Neusy[5]’ Goto[6p et al [?]I Yauwsberger]6p Prazosin Propranolol Prazesin Propranolol Prazosin Propranolol Prazesin
Summary of Prazosin Lipid Studies
Number of patients Duration of study
TABLE I
REFERENCES 1.
2. 3.
4.
5.
124
Rouffy J. Jaillard J: Comparative effects of prazosin and atenofol on plasma lipids in hypertensive patients. Am J Med 1984; 76 (suppl 2A): 105-108. Leren P: Effect of alpha- and beta-blocker therapy on blood lipids. Am J Med 1984; 76 (suppl 2A): 67-7 1. Kather Ii, Sauberlich P: Comparison of in vitro and in vivo effects of prazosin on lipid metabolism. Am J Med 1984; 76 (suppl 2A): 89-93. Takabatake T, Ohta M, Maekawa M, et al: Effects of long-term prazosin therapy on lipoprotein metabolism in hypertensive patients. Am J Med 1984; 76 (suppl 2A): 113-l 16. Lowenstein J, Neusy A-J: Effects of prazosin and propranolol
February
27, 1984
The American
Journal of Medicine
6.
7.
8.
on serum lipids in patients with essential hypertension. Am J Med 1984; 76 (suppl2A): 79-84. Goto Y: Effects of alpha- and beta-blocker antihypertensive therapy on blood lipids: a multicenter trial. Am J Med 1984; 76 (suppl 2A): 72-78. Johnson BF. Romero L. Johnson J, Marwaha R: Comparative effects of propranolol and prazosin upon serum lipids in thiazide-treated hypertensive patients. Am J Med 1984; 76 (suppl2A): 109- 112. Mauersberger H: Effect of prazosin on blood pressure and plasma lipids in patients receiving a beta-blocker and diuretic regimen. Am J Med 1984; 76 (suppl2A): 101-104.