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Effect of trimazosin on serum lipid profiles in hypertensive patients
Effect of trimazosin on serum lipid profiles hypertensive patients
in
Abnormalities in the serum lipid profile correlate strongly with the presence and severity of atherosclerosis. Increases in serum lipids and a reduction in high-density lipoprotein (HDL) cholesterol have been demonstrated following treatment with some beta blockers and diuretics, either alone or in combination. A new alpha-1-adrenoceptor antagonist, trimazosin, was studied to determine its effects on serum lipids. Ninety-six hypertensive patients were randomly assigned in double-blind fashion to trimarosin or placebo for 8 weeks. Trimazosin was associated with a significant reduction (p 5 0.01) in total cholesterol when compared with the placebo group. This effect was seen in all patients regardless of whether or not they were taking a diuretic concomitantly. In addition, a g-month, double-blind parallel comparison was made of trimazosin and propranolol. Trimarosin was found to be superior to propranolol in its effect on HDL cholesterol and the HDL/total cholesterol ratio. These studies have demonstrated that, in contrast to placebo and propranolol, trimarosin lowers total serum cholesterol without undesirable effects on other serum lipid fractions. When polythiaride is given concomitantly, it diminishes the favorable effects of trimazosin and accentuates the opposite, adverse effects of propranolol. (AM HEART J 106:1265, 1983.)
Walter
Singleton,
M.A., B.M., B.Ch., and Colin R. Taylor,
M.D.
Sandwich, England, and Groton, Conn.
According to the lipid hypothesis, several types of abnormalities of the lipoprotein profile predispose to the development of atheroma, leading to coronary heart disease, cerebrovascular disease, and other illnesses resulting from impairment of blood flow to tissues. High concentrations of total serum cholesterol, cholesterol-rich low-density lipoprotein (LDL), and triglyceride-rich very low density lipoprotein (VLDL), together with low concentrations of high-density lipoprotein (HDL), are closely correlated with the presence and severity of atherosclerosis. Although the causal relationship is not proved, the correlations are so strong that it is widely accepted that modification of abnormal serum lipid profiles is an important aim of drug treatment.‘e4 Increases in serum triglycerides and a fall in HDL cholesterol have been observed following treatment with some beta-adrenoceptor-blocking drugs,5-8 thiazide diuretics,g and combinations of these.‘O These changes were not observed after combined beta- and alpha-adrenoceptor blockade with labetalol.” Alpha-adrenoceptor blockade with prazosin results in
From
Pfizer
Central
Reprint requests: Kent CT13 9NJ,
Research. Walter England.
Singleton,
Pfizer
Central
Research,
Sandwich,
a fall in total serum cholesterol and serum triglyceride concentrations and an improvement in the HDL/LDL + VLDL cholesterol ratio.6 This report summarizes the effects of trimazosin, a new antihypertensive alpha-adrenoceptor antagonist, on serum lipid profiles in long-term open studies and in a double-blind comparison with placebo and propranolol in patients being treated for hypertension. METHODS Long-term comparison.
AND RESULTS open
studies
and
double-blind
placebo
After 1 year of open trimazosin therapy, 96 patients were randomly assigned in double-blind fashion either to continue taking trimazosin (mean dosage, 655 mg/day) for another 8 weeks or to receive placebo. Serum lipid parameters were measured in these patients. Of the 96 patients, 44 were taking polythiazide concomitantly (0.5 to 4 mg/day) during part or all of the 12-month
open-treatment period, and this wascontinued during the double-blind comparative phase. Not all patients had lipid values available at each of the three time points of interest for analysis (i.e., baseline,end of open trial, and end of double-blind trial). Thus patient numbers differ for each lipid parameter in the analysis of the open and double-blind parts of the study. There were no significant differences between the patient groups in terms of baseline values for all lipid parameters (Table I). For the open part of this study, comparisons were made 1265
1266
Singleton
Table
and Taylor
November, 1993 Heart Journal
1.Serum lipids at baselineand after long-term open trimazosin therapy Total Treatment groups
All patients Baseline End of open Patientsnot taking diuretics Baseline End of open Patients taking diuretics Baseline End of open
Table
American
serum cholesterol (m&W
HDL
-
cholesterol (mgldl)
Total
serum triglycerides (mgldl)
n
Mean
SEM
n
Mean
SEM
n
Mean
SEM
90 90
225.3
218.6
3.6 3.5
35 35
53.4 52.1
2.9 2.9
74 74
137.3 151.0
10.6 12.2
48 48
226.3 217.8
5.5 4.8
22 22
50.2 51.2
3.8 4.2
40 40
134.1 141.3
12.6 15.6
42 42
224.1 219.4
4.6 5.2
13 13
58.8 53.5
4.1 3.5
34 34
141.0 162.3
17.8 19.3
Total
serum triglycerides (mgldl)
II. Serum lipids before and after double-blind therapy Total
Treatment groups
Trimazosin BeforeDB End DB Placebo BeforeDB End DB No diuretics BeforeDB End DB Diuretics BeforeDB End DB DB = double-blind
serum cholesterol (mgldl)
HDL
cholesterol (mgldl)
n
Mean
SEM
n
Mean
SEM
n
Mean
SEM
44 44
220.2 210.7
5.3 4.4
17 17
47.2 46.1
3.8 3.3
44 44
130.3 126.4
10.1 10.7
42 42
220.8 232.3
5.1 5.5
18 18
57.0 50.3
4.2 3.4
42 42
157.4 177.3
16.6 21.1
43 43
220.8 220.4
4.9 5.7
19 19
53.0 48.3
4.7 3.3
43 43
128.3 121.6
11.1 10.8
43 43
220.2 222.0
5.5 4.8
16 16
51.3 48.3
5.3 3.6
43 43
158.7 180.8
15.7 20.4
therapy.
between pretreatment values (i.e., at baseline)and values at the end of open therapy for total cholesterol, HDL cholesterol, and triglycerides (Table I). Trimazosin therapy was associatedwith significant reduction (p < 0.05) in total cholesterol from baseline;this effect was seenin all patients whether or not they were taking diuretics. For the double-blind part of this study, comparisons were made between values before double-blind therapy (i.e., end of open therapy) and values at the end of double-blind therapy for total cholesterol, HDL cholesterol, and triglycerides. During the double-blind phase, trimazosin was associated with a significant reduction (p < 0.01) in total cholesterol when compared with the placebo group; there were no significant effects after diuretic useor becauseof interaction betweendiuretic and drug. During the g-week double-blind period, patients receiving trimazosin experienced a reduction of 9.5 mg/dl in total cholesterol, whereasthose taking placebo experienced an increaseof 11.5 mg/dl in total cholesterol (Table II).
There were no significant effects of trimazosin on HDL cholesterol or triglycerides during double-blind therapy. Long-term propranolol.
double-blind
comparison
of trimazosln
and
The indication of potentially beneficial effects of trimazosin therapy on serum lipids, asdescribed previously, prompted a further investigation of these laboratory parameters in a ‘I-month double-blind parallel comparison of trimazosin (100 to 400 mg/day) and propranolol (80 to 320 n&day) in hypertensive patients. Patients received trimazosin or propranolol alone for the initial 12 weeks of therapy, after which time diuretic therapy (polythiazide up to 1 mg/day) could be added for patients who required additional antihypertensive effect. Data analysis was performed both after 12 weeks of therapy (without concomitant administration of a thiazide diuretic) and after 7 months of therapy (with a thiazide diuretic in less-than-optimum responders). After 12 weeksof therapy (Table III), when the mean daily dosesof trimazosin and propranolol were 291 and 208 mg/day, respectively, and when no patients were
Volume Number
106 5, Part 2
Trimazosin’s
effects on serum lipids
1267
Ill. Lipid values after 12-week double-blind treatment with trimazosin or propranolol (mean at baseline, change +- SEM after treatment)
Table
Trimazosin
Parameter Total
HDL
Total
cholesterol
cholesterol
triglycerides
*t Test on difference
(mg/dl)
Baseline Change n Baseline Change n Baseline Change n
(mg/dl)
(mg/dl)
between treatment
Statistical significance
Propranolol
266 Z!I 4.1 65 50.0 1.4 -I- 1.1 65 135 -8.4 + 7.8 57
262 + 5.0 63 51.5 -4.4 * 1.2 62 138 -5.4 + 8.0 58
-12.8
-8.5
*
NS
p < 0.001
NS
of mean changes from baseline.
IV. Mean change from baseline (+SEM) after 7 months of double-blind trimazosin or propranolol therapy ( * polythiazide)*
Table
Trimatosin Alone
Lipids Total
cholesterol
(mg/dl)
HDL
cholesterol
(mg/dl)
Total
triglycerides
*Analysis
of variance:
(mg/dl)
p < 0.001, trimazosin
Mean SE n Mean SE n Mean SE n vs propranolol,
-5.7 5.4 35 +5.2 1.6 35 -17.1 14.2 33 for HDL
cholesterol;
receiving polythiazide, trimazosin wasfound to be superior to propranolol in its effects on HDL cholesterol (p < 0.001). Trimazosin also tended to be superior to propranolol in its effects on concentrations of total serum cholesterol and total serum triglycerides, although these differences were not statistically significant. Consequently, the HDL/total cholesterolratio of the trimazosin group significantly improved compared with that of the propranolol group (+8.3 % from baseline versus -2.6% ;
Propranolol +Diuretic -3.6 7.2 30 -0.1 2.0 30 +16.0 16.6 25
p < 0.05, diuretic
YS no diuretic,
Alone -2.0 4.8 45 -2.7 1.2 44 +14.7 9.1 41
+Diuretic +2.9 8.4 16 -6.1 2.8 16 +12.4 19.5 16
for HDL cholesterol.
ratio with trimazosin were +1.5% from baseline versus -12.1% from baselinewith propranolol. In summary, when comparedwith placebo, propranolol, and thiazide use,trimazosin therapy resulted in favorable changesin the plasmacholesterol fractions. The effect of polythiazide was, in part, to antagonize the favorable effects of trimazosin and to accentuate the adverseeffects of propranolol.
p < 0.05).
CONCLUSIONS
After 7 months of therapy, at a time when 46% of trimazosin patients and 26% of propranolol patients were receiving concomitant diuretic therapy, trimazosin (mean dose 308 mglday) was again found to be superior to propranolol (mean dose, 218 mg/day) in its effects on HDL cholesterol (p < 0.001; Table IV) and the HDL/total cholesterol ratio. Thiazide use had a significantly worse effect (p < 0.05) on HDL cholesterol and the HDL/total cholesterol ratio than did therapy without thiazides. The changesfor the HDL/total cholesterol ratio were +13.4% from baselinewith trimazosin versus -5.8% from baseline with propranolol in those patients not receiving concomitant diuretic therapy. In patients receiving concomitant diuretic therapy, the changes for HDL/total cholesterol
Trimazosin has been shown in many clinical studies to be an effective, well-tolerated antihyper-
tensive agent. 12-16The studies summarized here demonstrate that trimazosin does not share the adverse effect on serum cholesterol fractions associated with the use of some beta-adrenoceptor antagonists and diuretics commonly used in the management of hypertension. Indeed, those changes induced by trimazosin could be regarded as having a beneficial effect in terms of the risk of cardiovascular morbidity. Despite many extensive clinical trials, the most recent of which is the Multiple Risk Factor Inter-
November,
1266
Singleton
and Taylor
vention Trial,17 the expected life-saving benefits of aggressive risk factor reduction have not been conclusively demonstrated. Nevertheless, it is undesirable that drugs used for the treatment of coronary heart disease, hypertension, and other vascular disorders should predispose to either the development or exacerbation of any risk factor. Drugs whose use is associated with lowering of total cholesterol and triglyceride levels and with the maintenance of HDL cholesterol are to be preferred for these conditions, especially in the treatment of young patients who may require life-long therapy. REFERENCES
Carlson LA, B&tiger LE: Ischaemic heart disease in relation to fasting values of plasma triglycerides and cholesterol. Lancet 1:865-868, 1972. Frederickson DS, Levy RI, Lees RS: Fat transport and lipoproteins-an integrated approach to mechanisms and disorders. N Engl J Med 276:34-44,94-103, 148-156,215-225, 273-281, 1976. Kannel WB, Dawber TR, Friedman GD, Glennon WE, MacNamara PM: Risk factors in coronary heart disease: An evaluation of several serum lipids as predictors of coronary heart disease. Ann Intern Med 61:888-899, 1964. Keys A, Aravanis C, Blackburn H, Van Buchem FSP, Bunina R, Djordjevik BS, Fidanza F, Karvonen M, Menotti A, Puddu V. Taylor HL: Probability of middle-aged men developing heart disease in five years. Circulation 45:815-828, 1972.
American
5. Day
6.
7. 8. 9.
10.
11. 12. 13.
14.
15.
16.
17.
Heart
1993 Journal
JL, Simpson N, Metcalfe J, Page RL: Metabolic consequences of atenolol and propranolol in treatment of hypertension. Br Med J 1:77, 1979. Leren P, Foss PO, Helgeland A, Hjermann I, Holme I, Lund-Larsen PG: Effect of propranolol and prazosin on blood lipids. Lancet 2:4, 1980. Shaw J, England JDF, Hua ASP: Beta-blockers and plasma triglycerides. Br Med J 1:986, 1978. Lehtonen A, Viikan J: Long-term effects of sotalol on plasma lipids. Clin Sci 57:405, 1979. Ames RP, Hill P: Increase in serum lipids during treatment of hypertension with chlorthalidone. Lancet 1:721, 1976. Helgeland A, Hjermann I, Leren P, Enger S, Holme I: High-density lipoprotein cholesterol and antihypertensive drugs: The Oslo study. Br Med J 2:403, 1978. McGonigle RJS. Williams L, Murphy MJ, Parsans V: Labetalol and lipids. Lancet 1:163, 1981. De Guia D, Mendlowitz M, et al: The effect of trimazosin in essential hypertension. Curr Ther Res 15:339, 1973. Vlachakis ND, Mendlowitz M, De Guzman D: Treatment of essential hypertension with trimazosin, a new vasodilator agent. Curr Ther Res 17:564, 1975. Aronow WS, Tobias J, Hughes D, et al: Comparison of trimazosin and methyldopa in hypertension. Clin Pharmacol Ther 22:425, 1977. Aronow WS, Oberman A, Pool PE, et al: Effect of trimazosin, methyldopa and placebo on hypertension. Curr Ther Res Clin Exp 23:448, 1978. Chrysant SG, Miller RF, Brown JL, Danisa K: Long-term hemodynamic and metabolic effects of trimazosin in essential hypertension. Clin Pharmacol Ther 30:600, 1981. Multiple Risk Factor Intervention Trial: Risk factor changes and mortality results. JAMA 248:1465, 1982.
in
Abnormalities in the serum lipid profile correlate strongly with the presence and severity of atherosclerosis. Increases in serum lipids and a reduction in high-density lipoprotein (HDL) cholesterol have been demonstrated following treatment with some beta blockers and diuretics, either alone or in combination. A new alpha-1-adrenoceptor antagonist, trimazosin, was studied to determine its effects on serum lipids. Ninety-six hypertensive patients were randomly assigned in double-blind fashion to trimarosin or placebo for 8 weeks. Trimazosin was associated with a significant reduction (p 5 0.01) in total cholesterol when compared with the placebo group. This effect was seen in all patients regardless of whether or not they were taking a diuretic concomitantly. In addition, a g-month, double-blind parallel comparison was made of trimazosin and propranolol. Trimarosin was found to be superior to propranolol in its effect on HDL cholesterol and the HDL/total cholesterol ratio. These studies have demonstrated that, in contrast to placebo and propranolol, trimarosin lowers total serum cholesterol without undesirable effects on other serum lipid fractions. When polythiaride is given concomitantly, it diminishes the favorable effects of trimazosin and accentuates the opposite, adverse effects of propranolol. (AM HEART J 106:1265, 1983.)
Walter
Singleton,
M.A., B.M., B.Ch., and Colin R. Taylor,
M.D.
Sandwich, England, and Groton, Conn.
According to the lipid hypothesis, several types of abnormalities of the lipoprotein profile predispose to the development of atheroma, leading to coronary heart disease, cerebrovascular disease, and other illnesses resulting from impairment of blood flow to tissues. High concentrations of total serum cholesterol, cholesterol-rich low-density lipoprotein (LDL), and triglyceride-rich very low density lipoprotein (VLDL), together with low concentrations of high-density lipoprotein (HDL), are closely correlated with the presence and severity of atherosclerosis. Although the causal relationship is not proved, the correlations are so strong that it is widely accepted that modification of abnormal serum lipid profiles is an important aim of drug treatment.‘e4 Increases in serum triglycerides and a fall in HDL cholesterol have been observed following treatment with some beta-adrenoceptor-blocking drugs,5-8 thiazide diuretics,g and combinations of these.‘O These changes were not observed after combined beta- and alpha-adrenoceptor blockade with labetalol.” Alpha-adrenoceptor blockade with prazosin results in
From
Pfizer
Central
Reprint requests: Kent CT13 9NJ,
Research. Walter England.
Singleton,
Pfizer
Central
Research,
Sandwich,
a fall in total serum cholesterol and serum triglyceride concentrations and an improvement in the HDL/LDL + VLDL cholesterol ratio.6 This report summarizes the effects of trimazosin, a new antihypertensive alpha-adrenoceptor antagonist, on serum lipid profiles in long-term open studies and in a double-blind comparison with placebo and propranolol in patients being treated for hypertension. METHODS Long-term comparison.
AND RESULTS open
studies
and
double-blind
placebo
After 1 year of open trimazosin therapy, 96 patients were randomly assigned in double-blind fashion either to continue taking trimazosin (mean dosage, 655 mg/day) for another 8 weeks or to receive placebo. Serum lipid parameters were measured in these patients. Of the 96 patients, 44 were taking polythiazide concomitantly (0.5 to 4 mg/day) during part or all of the 12-month
open-treatment period, and this wascontinued during the double-blind comparative phase. Not all patients had lipid values available at each of the three time points of interest for analysis (i.e., baseline,end of open trial, and end of double-blind trial). Thus patient numbers differ for each lipid parameter in the analysis of the open and double-blind parts of the study. There were no significant differences between the patient groups in terms of baseline values for all lipid parameters (Table I). For the open part of this study, comparisons were made 1265
1266
Singleton
Table
and Taylor
November, 1993 Heart Journal
1.Serum lipids at baselineand after long-term open trimazosin therapy Total Treatment groups
All patients Baseline End of open Patientsnot taking diuretics Baseline End of open Patients taking diuretics Baseline End of open
Table
American
serum cholesterol (m&W
HDL
-
cholesterol (mgldl)
Total
serum triglycerides (mgldl)
n
Mean
SEM
n
Mean
SEM
n
Mean
SEM
90 90
225.3
218.6
3.6 3.5
35 35
53.4 52.1
2.9 2.9
74 74
137.3 151.0
10.6 12.2
48 48
226.3 217.8
5.5 4.8
22 22
50.2 51.2
3.8 4.2
40 40
134.1 141.3
12.6 15.6
42 42
224.1 219.4
4.6 5.2
13 13
58.8 53.5
4.1 3.5
34 34
141.0 162.3
17.8 19.3
Total
serum triglycerides (mgldl)
II. Serum lipids before and after double-blind therapy Total
Treatment groups
Trimazosin BeforeDB End DB Placebo BeforeDB End DB No diuretics BeforeDB End DB Diuretics BeforeDB End DB DB = double-blind
serum cholesterol (mgldl)
HDL
cholesterol (mgldl)
n
Mean
SEM
n
Mean
SEM
n
Mean
SEM
44 44
220.2 210.7
5.3 4.4
17 17
47.2 46.1
3.8 3.3
44 44
130.3 126.4
10.1 10.7
42 42
220.8 232.3
5.1 5.5
18 18
57.0 50.3
4.2 3.4
42 42
157.4 177.3
16.6 21.1
43 43
220.8 220.4
4.9 5.7
19 19
53.0 48.3
4.7 3.3
43 43
128.3 121.6
11.1 10.8
43 43
220.2 222.0
5.5 4.8
16 16
51.3 48.3
5.3 3.6
43 43
158.7 180.8
15.7 20.4
therapy.
between pretreatment values (i.e., at baseline)and values at the end of open therapy for total cholesterol, HDL cholesterol, and triglycerides (Table I). Trimazosin therapy was associatedwith significant reduction (p < 0.05) in total cholesterol from baseline;this effect was seenin all patients whether or not they were taking diuretics. For the double-blind part of this study, comparisons were made between values before double-blind therapy (i.e., end of open therapy) and values at the end of double-blind therapy for total cholesterol, HDL cholesterol, and triglycerides. During the double-blind phase, trimazosin was associated with a significant reduction (p < 0.01) in total cholesterol when compared with the placebo group; there were no significant effects after diuretic useor becauseof interaction betweendiuretic and drug. During the g-week double-blind period, patients receiving trimazosin experienced a reduction of 9.5 mg/dl in total cholesterol, whereasthose taking placebo experienced an increaseof 11.5 mg/dl in total cholesterol (Table II).
There were no significant effects of trimazosin on HDL cholesterol or triglycerides during double-blind therapy. Long-term propranolol.
double-blind
comparison
of trimazosln
and
The indication of potentially beneficial effects of trimazosin therapy on serum lipids, asdescribed previously, prompted a further investigation of these laboratory parameters in a ‘I-month double-blind parallel comparison of trimazosin (100 to 400 mg/day) and propranolol (80 to 320 n&day) in hypertensive patients. Patients received trimazosin or propranolol alone for the initial 12 weeks of therapy, after which time diuretic therapy (polythiazide up to 1 mg/day) could be added for patients who required additional antihypertensive effect. Data analysis was performed both after 12 weeks of therapy (without concomitant administration of a thiazide diuretic) and after 7 months of therapy (with a thiazide diuretic in less-than-optimum responders). After 12 weeksof therapy (Table III), when the mean daily dosesof trimazosin and propranolol were 291 and 208 mg/day, respectively, and when no patients were
Volume Number
106 5, Part 2
Trimazosin’s
effects on serum lipids
1267
Ill. Lipid values after 12-week double-blind treatment with trimazosin or propranolol (mean at baseline, change +- SEM after treatment)
Table
Trimazosin
Parameter Total
HDL
Total
cholesterol
cholesterol
triglycerides
*t Test on difference
(mg/dl)
Baseline Change n Baseline Change n Baseline Change n
(mg/dl)
(mg/dl)
between treatment
Statistical significance
Propranolol
266 Z!I 4.1 65 50.0 1.4 -I- 1.1 65 135 -8.4 + 7.8 57
262 + 5.0 63 51.5 -4.4 * 1.2 62 138 -5.4 + 8.0 58
-12.8
-8.5
*
NS
p < 0.001
NS
of mean changes from baseline.
IV. Mean change from baseline (+SEM) after 7 months of double-blind trimazosin or propranolol therapy ( * polythiazide)*
Table
Trimatosin Alone
Lipids Total
cholesterol
(mg/dl)
HDL
cholesterol
(mg/dl)
Total
triglycerides
*Analysis
of variance:
(mg/dl)
p < 0.001, trimazosin
Mean SE n Mean SE n Mean SE n vs propranolol,
-5.7 5.4 35 +5.2 1.6 35 -17.1 14.2 33 for HDL
cholesterol;
receiving polythiazide, trimazosin wasfound to be superior to propranolol in its effects on HDL cholesterol (p < 0.001). Trimazosin also tended to be superior to propranolol in its effects on concentrations of total serum cholesterol and total serum triglycerides, although these differences were not statistically significant. Consequently, the HDL/total cholesterolratio of the trimazosin group significantly improved compared with that of the propranolol group (+8.3 % from baseline versus -2.6% ;
Propranolol +Diuretic -3.6 7.2 30 -0.1 2.0 30 +16.0 16.6 25
p < 0.05, diuretic
YS no diuretic,
Alone -2.0 4.8 45 -2.7 1.2 44 +14.7 9.1 41
+Diuretic +2.9 8.4 16 -6.1 2.8 16 +12.4 19.5 16
for HDL cholesterol.
ratio with trimazosin were +1.5% from baseline versus -12.1% from baselinewith propranolol. In summary, when comparedwith placebo, propranolol, and thiazide use,trimazosin therapy resulted in favorable changesin the plasmacholesterol fractions. The effect of polythiazide was, in part, to antagonize the favorable effects of trimazosin and to accentuate the adverseeffects of propranolol.
p < 0.05).
CONCLUSIONS
After 7 months of therapy, at a time when 46% of trimazosin patients and 26% of propranolol patients were receiving concomitant diuretic therapy, trimazosin (mean dose 308 mglday) was again found to be superior to propranolol (mean dose, 218 mg/day) in its effects on HDL cholesterol (p < 0.001; Table IV) and the HDL/total cholesterol ratio. Thiazide use had a significantly worse effect (p < 0.05) on HDL cholesterol and the HDL/total cholesterol ratio than did therapy without thiazides. The changesfor the HDL/total cholesterol ratio were +13.4% from baselinewith trimazosin versus -5.8% from baseline with propranolol in those patients not receiving concomitant diuretic therapy. In patients receiving concomitant diuretic therapy, the changes for HDL/total cholesterol
Trimazosin has been shown in many clinical studies to be an effective, well-tolerated antihyper-
tensive agent. 12-16The studies summarized here demonstrate that trimazosin does not share the adverse effect on serum cholesterol fractions associated with the use of some beta-adrenoceptor antagonists and diuretics commonly used in the management of hypertension. Indeed, those changes induced by trimazosin could be regarded as having a beneficial effect in terms of the risk of cardiovascular morbidity. Despite many extensive clinical trials, the most recent of which is the Multiple Risk Factor Inter-
November,
1266
Singleton
and Taylor
vention Trial,17 the expected life-saving benefits of aggressive risk factor reduction have not been conclusively demonstrated. Nevertheless, it is undesirable that drugs used for the treatment of coronary heart disease, hypertension, and other vascular disorders should predispose to either the development or exacerbation of any risk factor. Drugs whose use is associated with lowering of total cholesterol and triglyceride levels and with the maintenance of HDL cholesterol are to be preferred for these conditions, especially in the treatment of young patients who may require life-long therapy. REFERENCES
Carlson LA, B&tiger LE: Ischaemic heart disease in relation to fasting values of plasma triglycerides and cholesterol. Lancet 1:865-868, 1972. Frederickson DS, Levy RI, Lees RS: Fat transport and lipoproteins-an integrated approach to mechanisms and disorders. N Engl J Med 276:34-44,94-103, 148-156,215-225, 273-281, 1976. Kannel WB, Dawber TR, Friedman GD, Glennon WE, MacNamara PM: Risk factors in coronary heart disease: An evaluation of several serum lipids as predictors of coronary heart disease. Ann Intern Med 61:888-899, 1964. Keys A, Aravanis C, Blackburn H, Van Buchem FSP, Bunina R, Djordjevik BS, Fidanza F, Karvonen M, Menotti A, Puddu V. Taylor HL: Probability of middle-aged men developing heart disease in five years. Circulation 45:815-828, 1972.
American
5. Day
6.
7. 8. 9.
10.
11. 12. 13.
14.
15.
16.
17.
Heart
1993 Journal
JL, Simpson N, Metcalfe J, Page RL: Metabolic consequences of atenolol and propranolol in treatment of hypertension. Br Med J 1:77, 1979. Leren P, Foss PO, Helgeland A, Hjermann I, Holme I, Lund-Larsen PG: Effect of propranolol and prazosin on blood lipids. Lancet 2:4, 1980. Shaw J, England JDF, Hua ASP: Beta-blockers and plasma triglycerides. Br Med J 1:986, 1978. Lehtonen A, Viikan J: Long-term effects of sotalol on plasma lipids. Clin Sci 57:405, 1979. Ames RP, Hill P: Increase in serum lipids during treatment of hypertension with chlorthalidone. Lancet 1:721, 1976. Helgeland A, Hjermann I, Leren P, Enger S, Holme I: High-density lipoprotein cholesterol and antihypertensive drugs: The Oslo study. Br Med J 2:403, 1978. McGonigle RJS. Williams L, Murphy MJ, Parsans V: Labetalol and lipids. Lancet 1:163, 1981. De Guia D, Mendlowitz M, et al: The effect of trimazosin in essential hypertension. Curr Ther Res 15:339, 1973. Vlachakis ND, Mendlowitz M, De Guzman D: Treatment of essential hypertension with trimazosin, a new vasodilator agent. Curr Ther Res 17:564, 1975. Aronow WS, Tobias J, Hughes D, et al: Comparison of trimazosin and methyldopa in hypertension. Clin Pharmacol Ther 22:425, 1977. Aronow WS, Oberman A, Pool PE, et al: Effect of trimazosin, methyldopa and placebo on hypertension. Curr Ther Res Clin Exp 23:448, 1978. Chrysant SG, Miller RF, Brown JL, Danisa K: Long-term hemodynamic and metabolic effects of trimazosin in essential hypertension. Clin Pharmacol Ther 30:600, 1981. Multiple Risk Factor Intervention Trial: Risk factor changes and mortality results. JAMA 248:1465, 1982.