Associating Metabolic Changes with Antihypertensive Therapy Antihypertensive drugs appear to aggravate abnormal lipid levels observed In patients ••.

In the Australian Risk Factor Prevalence Study. lipid levels were examined in 3454 normotensive subjects. 908 patients with untreated hypertension and 509 receiving antihypertensive drugs (age range 25 to 65 years).

At the time of the study. national statistics suggested that p-blockers. diuretics and methyldopa were frequently prescribed.

There was no significant difference in total cholesterol levels between treated and untreated hypertensive patients but levels were significantly lower in normotensive subjects. low density lipoprotein cholesterol levels were not significantly different in males from the 3 groups but untreated hypertensive women had significantly higher levels than normotensive women. Normotensive and untreated hypertenSive patients had similar high density lipoprotein cholesterol levels while levels were significantly lower in antihypertensive­treated patients. Triglyceride levels and the ratio of total cholesterol to high density lipoprotein cholesterol were significantly higher in untreated hypertensive males and females than in normotensive subjects. How· ever. antihypertensive-treated men also showed significantly higher levels than untreated men. Further. the percentage of antihypertensive-treated males with total cholesterol levels> 252 mg/dl. or with a ratio of total cholesterol to high density lipoprotein cholesterol of > 6. was significantly higher than in the untreated hypertensive group.

The authors concluded that ' ••• a large proportion of penon. with untrHted high blood ."...... are Ilkely to have substantially elevated levels of pia.,.,. lipid or lipoprotein choInteroI'. Further. antihypertensive therapy ' •• , Is likely to worsen the already poor plasma lipid and lipoprotein profiles of the average hyperten8ive patient', MacMahon SW. MacDonald GJ Ameflcan Journal 01 Medicine 80 (Suppl. 2A) 40-47. 14 Feb 1986

.• , while In open studies atenolol or prazosln •.• In an open multicentre study. 59 patients (aged 25-70 years) with BP of 160/95-200/120mm Hg received

titrated doses of atenolol 1()()-200mg once daily (n = 30) or prazosin 1-15 mg/day (n = 29). Treatment was for 6 months after a 1-month washout period.

There was a significant decrease in total cholesterol. low density lipoprotein cholesterol, triglycerides and apoprotein B levels in the prazosin-treated group and a corresponding significant increase in apoprotein A, and high density lipoprotein cholesterol levels with prazosin treatment. Atenolol-treated patients showed significant increases in total cholesterol. low density lipoprotein cholesterol. triglycerides. very low density lipoprotein triglycerides and apoprotein B levels and significant decreases in high density lipoprotein chol­esterol and apoprotein A1 levels. There was no change in high density lipoprotein2 cholesterol levels with either drug treatment between 0-6 months.

The consequences of the changes observed in blood lipid levels is not known but the '. , ,change. In the lipid profile may be responsible for atherogenic consequences similar to tho .. cauHd by a primary or secondary dysllpidemla'. Roulfy J. Jaillard J American Journal 01 Medicine 80 (Suppl 2A)' 1(J().103. 14 Feb 1986

•.. and metoprolol or prazosln alter lipid profile. In a randomised open trial. 30 patients (22 men and 8 women) of mean age 44 years, with mild to

moderate essential hypertenSion. received prazosin 0.5·1.0 mg/day (n = 15) or metoprolol 1()()'200 mg/day (n = 15) for 10 weeks.

Supine BP decreased significantly with prazosin from 153/102 to 146/92mm Hg and from 158/103 to 144j94mm Hg with metoprolol. Heart rate increased significantly from 73 to 77 beats/min with prazosin but decreased significantly from 74 to 56 beats/min with metoprolol treatment. Total serum cholesterol de­creased significantly and high density lipoprotein cholesterol and lipoprotein lipase activity increased sig· nificantly from baseline in prazosin-treated patients. High density lipoprotein cholesterol decreased signifi-

cantly and total triglycerides increased significantly from baseline in metoprolol-treated patients. The effects of P-blockers on lipid metabolism must be mediated via a mechanism other than lipoprotein

lipase while the absence of decreased serum triglyceride levels with prazosin therapy may be related to low normal levels in the patients treated. Ferrara LA. Marotta T. Rubba P, de Simone 8. Leccia G, et aI. American Journal of Medicine 80 (Suppl. 2A). 104-108. 14 Feb 1986

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Prazosin + atenolol displays metabolic advantages over propranolol + diuretic, , , In an open parallel trial. 20 well-controlled hypertensive patients (aged 58 to 62 years) treated with a fJ­

blocker + a diuretic and/or hydralazine received atenolol 50 mg/day instead of the fJ-blocker. or prazosin (mean dose 4.4 mg/day) instead of the diuretic or hydralazine. Five months later the alternative substitution was made.

With the substitution of prazosin for hydralazine or diuretics supine BP did not change significantly. Similarly. there was no change when atenolol replaced other fJ-blockers. Heart rate was not altered sig­nificantly.

Where prazosin replaced diuretics serum cholesterol and triglyceride concentrations decreased signifi­cantly (11 and 42%. respectively) but high density lipoprotein cholesterol. high density lipoprotein triglyc­eride and glucose metabolism did not show any significant changes. No significant changes occurred when prazosin replaced hydralazine or when atenolol replaced other fJ-blocker therapy except serum triglyceride levels decreased significantly when propranolol was replaced by atenolol. Thus. " , , a combination of 50mg of atenolol per day and prazosin has metabolic advantages over combination treatment with a diuretic and propranolol' ,

Lithetl H. Aberg H. Se/inus I. American Journal of Medicine 80 (Suppl.2A): 114-119. 14 Feb 1986

, .. and hydrochlorothiazide has a greater effect on glucose and potallium levels than prazosln In an open randomised trial. 62 hypertensive patients received titrated doses of prazosin 1-20 mg/day

(n = 32) or hydrochlorothiazide 25-50 mgjday (n = 30) for 1 year after a ~ 4-week placebo washout period. If, after 2 weeks, diastolic BP had not decreased to ~ 95mm Hg the alternative drug was added to the treatment regimen. 20 patients in the prazosin-treated group and 17 in the hydrochlorothiazide-treated group completed the study.

In patients who completed the study and were treated with prazosin alone (n = 10) BP decreased from 145j104mm Hg to 135j89mm Hg (NS/p < 0.(01). Patients who required hydrochlorothiazide in addition to prazosin (n = 10) showed an initial significant BP decrease from 156/108mm Hg to 143/96mm Hg with prazosin alone and then to 136/92mm Hg with the combined treatment (NS). Hydrochlorothiazide treatment alone (n = 9 excluding 3 atenolol recipients) resulted in a significant BP decrease from 146/102mm Hg to 128/86mm Hg.

In patients treated with hydrochlorothiazide + prazosin (n = 5) BP decreased significantly from 150/ 110mm Hg to 131/95mm Hg with hydrochlorothiazide. However, when prazosin was added to the regimen the subsequent decrease in BP did not reach significance (133f95mm Hg).

Fasting blood glucose and cholesterol levels decreased in patients receiving prazosin and potassium levels decreased in patients receiving either drug but no changes were significant compared with baseline. A significantly greater number of diuretic recipients did, however, have potassium levels ~ 4 mEq. Chol­esterol and fasting blood glucose levels increased in patients receiving hydrochlorothiazide, although again no changes were significant compared with baseline.

Four prazosin recipients withdrew from the study because of palpitations (n = 1) or dizziness (n = 3) and 2 combination recipients also discontinued treatment because of the latter effect. Other adverse events reported during the study included headache. lack of energy, leg cramps and gastrOintestinal complaints. However, the authors concluded that prazosin and hydrochlorothiazide appear to be " ,. equally acceptable and effective hypotensive agents',

Alderman MH. Davis TK. Carroll L American Journal of Medicine 80 (Suppl. 2A): 1~125. 14 Feb 1986

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