Minoxidil in severe hypertension with renal failure. Effect of its addition to conventional antihypertensive drugs

Minoxidil, a new vasodilator antihypertensive compound, was given to 9 uremic patients with severe hypertension uncontrollable with currently available drugs. Addition of minoxidil in doses of 5 to 10 mg twice daily to their prior therapy, resulted in satisfactory control of blood pressure in all patients. Supine blood pressure fell from a control value of 200 ± 6/124 ± 3 to 164 ± 5/91 ± 2 mm Hg (mean and standard error) after administration of minoxidil, and no patient experienced orthostatic hypotension. Tachyphylaxis has not been seen during a follow-up period averaging 26 weeks. Side effects resulting from minoxidil have been limited to mild hypertrichosis in 2 patients, nausea in another 2 and fluid retention, which was readily controlled by either hemodialysis or furosemide. Minoxidil appears, therefore, to provide a means for controlling blood pressure in patients with severe hypertension resistant to all other antihypertensive drugs.     

Effects of captopril and minoxidil on left ventricular hypertrophy in resistant hypertensive patients: a 6 month double-blind comparison

In a double-blind 6 month trial, the cardiac effects of captopril and minoxidil, administered as third step treatments, were compared in 34 men with essential hypertension and diastolic blood pressure greater than 95 mm Hg who were taking 200 mg/day of metoprolol and 80 mg/day of furosemide. Average daily doses of captopril and minoxidil were 269 mg (range 150 to 300) and 20 mg (range 7.5 to 30), respectively. At the end of the 6 months' treatment, blood pressure had dropped significantly in both groups, but echocardiographic criteria of hypertrophy improved only in the captopril group (intragroup comparison): blood pressure, thickness of the intraventricular septum and posterior wall, and the left ventricular mass index, respectively, decreased from 163/102 to 135/89 mm Hg (p less than 0.001), 17.4 to 15.9 mm (p less than 0.05), 14.5 to 13.4 mm (p less than 0.05) and 236 to 198 g/m2 (p less than 0.001). In the minoxidil group, blood pressure dropped from 160/99 to 137/87 mm Hg (p less than 0.001), but echocardiographic criteria were not significantly modified. Fractional shortening remained normal in both groups. These results show that in patients with severe left ventricular hypertrophy, captopril-based triple therapy reduces left ventricular mass without altering systolic performance, whereas minoxidil-based therapy does not.     

Antihypertensive efficacy of once daily MK-521, a new nonsulfhydryl angiotensin-converting enzyme inhibitor

The effects of the new nonsulfhydryl-containing oral converting-enzyme inhibitor MK-521 on blood pressure, heart rate, angiotensin-converting enzyme activity, plasma renin activity and plasma aldosterone concentration were assessed in 10 hypertensive patients. After a 2-week no-treatment period, patients received placebo and then 14 days each: MK-521 20 mg once daily, hydrochlorothiazide 50 mg once daily and the latter 2 in combination. During the last day of each treatment, the mean (+/- standard deviation) time-averaged (1- to 12-hour) standing diastolic blood pressure decreased from 106 +/- 8 (placebo) to 95 +/- 10 mm Hg with MK-521, 95 +/- 13 mm Hg with hydrochlorothiazide (p less than 0.05 vs placebo) and 88 +/- 11 mm Hg with the combination (p less than 0.05 vs all other treatments). The antihypertensive effect of MK-521 was maintained 24 hours after dosing. Heart rate did not change significantly after MK-521 treatment. MK-521 caused a marked suppression of converting enzyme activity for over 24 hours; plasma renin activity increased significantly after each active treatment and MK-521 significantly decreased the hydrochlorothiazide-induced elevation of plasma aldosterone concentration. In this short-term trial, MK-521 was well tolerated.     

Long-term treatment of severe hypertension with minoxidil, propranolol and furosemide.

Thirteen patients with severe hypertension were treated with combined minoxidil, propranolol, and furosemide (mean daily doses 33 mg, 475 mg, and 578 mg, respectively) for nine to twenty-five months (mean 13.8). Average mean blood pressure while on aggressive therapy with conventional medication was 144 +/- 14 mm Hg; on minoxidil and propranolol it was 108 "/- 10 mm Hg (P less thator to optimum blood pressure control and required large doses of furosemide to control. Propranolol blunted the reflex tachycardia associated with arteriolar dilator therapy but all patients continued with a clinically hyperdynamic circulation. Seven of seven had elevated ejection fractions on echocardiogram, and two of three had elevated cardiac indices. Three of three who had heart catheterization had pulmonary hypertension which was aggravated by exercise. An additional three patients on hydralazine, propranolol, and furosemide also had pulmonary hypertension suggesting this is not unique to minoxidil. Two of thirteen developed pericardial effusions. Renal function improved in three and worsened in three.     

Candesartan cilexetil and renal hemodynamics in hypertensive patients

This randomized, double-blind, placebo-controlled crossover study evaluated the effects of the angiotensin II type 1 (AT1)-receptor blocker candesartan cilexetil on renal blood perfusion and glomerular filtration in patients with primary hypertension with diastolic blood pressure of 100 to 114 mm Hg. After a 4-week placebo run-in period, patients were randomized to receive either 16 mg candesartan cilexetil or placebo once daily for 6 weeks, after which they were switched to the alternative treatment. At the end of each period, 24 h after the last dose, renal assessments were made and the plasma renin activity, plasma concentrations of angiotensin II, aldosterone, and catecholamines were measured. Compared with placebo, candesartan cilexetil significantly reduced mean arterial pressure, by 8 mm Hg (95% confidence interval [CI], 3;12). Renal vascular resistance was significantly reduced by 0.03 mm Hg/mL min(-1) (95% CI, 0.01; 0.06). There was a small nonsignificant increase in renal plasma flow. The filtration fraction fell slightly from 0.24 to 0.22 (95% CI, -0.00, 0.04). As expected, angiotensin II concentrations and plasma renin activity were increased and the aldosterone concentrations were reduced. Catecholamine concentrations were unaffected. In conclusion, 6 weeks' treatment with 16 mg candesartan cilexetil once daily induced a reduction of renal vascular resistance and a trend toward increased renal plasma flow despite a reduction in mean arterial pressure. Because the glomerular filtration rate was maintained the filtration fraction was reduced, indicating a decreased glomerular capillary pressure.     

Antihypertensive effect of a new dihydropyridine calcium antagonist, PN 200-110 (isradipine), combined with pindolol

Preliminary results of a randomized, double-blind, placebo-controlled trial of PN 200-110 (isradipine) are reported. The study involves 5 centers and 61 patients with essential hypertension. Either PN 200-110 or placebo was added to an ongoing daily regimen of 10 mg of pindolol to determine if this agent would enhance the effect of the beta-adrenoreceptor blocking agent. PN 200-110 was given twice daily, starting with a dose of 2.5 mg or 5 mg, which could be doubled after 4 weeks. The average final dose was 6.3 mg given twice daily. Supine blood pressure was significantly reduced from a mean of 162/103 mm Hg to 144/88 mm Hg (p less than 0.001) in the patients who received the combination therapy. Heart rate did not change significantly. In 3 patients therapy was withdrawn, 1 during placebo and 2 during active treatment, owing to definite or suspected side effects.     

Prazosin versus propranolol plus prazosin: a comparison in diuretic-treated hypertensive patients

The antihypertensive efficacy of prazosin was compared with that of a combination of prazosin and propranolol in 14 patients with essential hypertension. All patients had sitting diastolic blood pressures greater than or equal to 95 mm Hg despite daily therapy with 50 mg of hydrochlorothiazide and 240 mg of propranolol. After a 4-week monitoring period, patients were divided randomly into 2 groups in whom either (1) propranolol was reduced to 120 mg/day (to avoid potential hypotension) and prazosin was added, starting with an initial dose of 1 mg twice daily, or (2) propranolol was tapered and discontinued as prazosin was added. The average doses of prazosin were 7.4 and 7.6 mg/day, respectively. After 12 weeks of therapy, blood pressure was reduced in both groups, and there was no significant difference in the reduction of blood pressure or dose of prazosin in the 2 groups. Mean heart rate increased significantly in both groups (p less than 0.01), but more so in the group of patients who discontinued propranolol therapy. Thus, when a combination of 50 mg/day of hydrochlorothiazide and 240 mg/day of propranolol is insufficient to control hypertension, the addition of prazosin is shown to decrease blood pressure whether or not propranolol is continued.     

The vasodilator minoxidil in the treatment of hypertension

A new vasodilating agent, minoxidil, was used in 17 patients with essential hypertension that had not responded sufficiently to combined treatment with 3 or 4 conventional hypotensive agents. After minoxidil was added, mean arterial BP dropped by 50 +/- 2.4 mmHg, the effect persisting for 3-4 months. Discontinuation of minoxidil after a short-term administration of 20 +/- 3.8 mg daily was accompanied with a BP rise eventually reaching baseline values, while gradual replacement with nifedipine after daily doses of minoxidil had been reduced smoothly over 3 or 4 weeks allowed to maintain mean arterial BP about 34 +/- 1.8 mm Hg below the baseline. The use of minoxidil in combination with beta-blockers and diuretics for 6 weeks resulted in a significant increase of left-ventricular myocardial weight, while cardiac contractility and pump function remained intact, as evidenced by electrocardiography. After 3 weeks of treatment, peripheral vascular resistance diminished in the forearm owing to reduced arterial and arteriolar tone, yet no reverse development of the vascular-wall adaptive structural changes could be seen at venous occlusion plethysmography.     

Comparison of the effect of captopril and minoxidil on left ventricular mass. Results of a 6-month comparative double-blind test

A randomised double blind study was performed in order to compare the cardiac effects of captopril and minoxidil in a subset of patients with severe primitive hypertension, uncontrolled (diastolic BP greater than 100 mmHg) by Metroprolol 200 mg/d and Furosemide 80 mg/d. 25 male pts completed the six month study, 33 pts having been excluded before randomisation (22 inadequate echoes) and 20 after randomisation (7 ambiguities on wall measurement). Average captopril dosage was 265 mg/d (150-300 mg), average minoxidil dosage was 19.6 mg/d (7.5-30 mg), dosages of Furosemide, Spironolactone and Metroprolol were similar in the two groups. Blood pressure decreased dramatically with both regimens (208/130 to 148/96 with captopril, 194/115 to 154/100 with minoxidil). Sokolow index was at the upper range of normal and decreased with both drugs. Cardiothoracic ratio decreased only with captopril. Echocardiograms were performed and read blindly at the end of the study. LV mass was measured according to Devereux, method. All patients had severe LVH. After 6 months posterior wall thickness decreased from 14.8 to 13.8 mm with captopril, remained stable from 14.1 to 14.9 mm with minoxidil, septal thickness decreased from 17.2 to 15.7 mm with captopril and remained stable (14.8 to 15.2 mm) with minoxidil. LV mass and mass index respectively decreased from 456 g and 232 g/m2 to 372 g and 190 g/m2 with captopril, and remained unchanged from 413 g and 215 g/m2 to 420 g and 218 g/m2 with minoxidil. Fractional shortening remained normal in both groups. Intra patients reproducibility was suboptimal because of difficulties in precise delineation of the endocardium in the severely hypertrophied ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Twice-daily administration of oral verapamil in the treatment of essential hypertension

The antihypertensive effect of twice-daily administration of verapamil hydrochloride was evaluated in 21 adult patients with mild to moderate essential hypertension. Following four weeks of placebo therapy, verapamil was given for four weeks with a treatment goal of sitting diastolic blood pressure (BP) of less than 90 mm Hg, or to a maximum dose of 160 mg twice daily. Sitting and standing BPs, heart rate, and verapamil plasma levels were determined weekly, ten to 12 hours post dose. At the maximal dose (mean, 154 +/- 19.2 mg), heart rate was not affected, side effects were minimal, and sitting diastolic BP was significantly reduced from placebo baseline, with 12 of 21 patients having a fall in sitting diastolic BP of 10 mm Hg or more or less than 90 mm Hg. A trough verapamil plasma level of greater than 80 ng/mL was associated with a good hypotensive response. These data indicate the safety and utility of twice-daily verapamil administration for the treatment of essential hypertension and suggest the value of obtaining verapamil plasma levels as a guide to dosage determination.     

LONG TERM MINOXIDIL THERAPY and RENAL FUNCTION, CARDIAC FUNCTION, HYPERTRICHOSIS and BLOOD PRESSURE

Twenty-eight patients with severe, refractory hypertension were treated with minoxidil, in combination with a beta-blocker and a diuretic, for periods ranging from 1.5 to 39 months. In 16 patients treated for more than a year (14 to 39 months, average 24) mean supine blood pressure fell from 209/115 mmHg to 163/87 mmHg at one year and 157/87 mmHg when last seen; mean standing blood pressure fell from 186/109 mmHg to 148/86 mmHg at one year and 147/88 mmHg when last seen. Minoxidil did not cause postural dizziness. Six patients with renal artery stenosis were treated for 1.5 to 11 months in preparation for renovascular surgery. Only one of 28 patients developed resistance to minoxidil (up to 80 mg daily) after an initial response. Nine of the 16 patients treated for more than a year had plasma creatinine levels in excess of 0.20 mmol/l before commencing minoxidil. In three of them, levels increased further during treatment. In the remaining 13 patients, mean creatinine levels after one year and when last seen were not higher than pre-treatment levels. All patients experienced fluid retention and hypertrichosis after commencing minoxidil. These effects were always controllable but very large doses of frusemide and the use of depilatory creams were sometimes required. The average dose of frusemide was 240 mg daily. Treatment did not have to be ceased because of these side-effects. Serial echocardiography revealed no evidence of pericardial effusion, and a significant reduction in estimated mean left ventricular mass in ten patients followed for at least one year. It is concluded that minoxidil is an effective agent in the long-term treatment of severe, resistant hypertension not responding to more conventional therapy. Provided that fluid retention and hypertrichosis were anticipated and treated vigorously when they arose, its use was not associated with any other serious problems.     

Minoxidil in severe hypertension: value when conventional drugs have failed.

Twenty-six patients were selected for treatment with minoxidil on the basis of hypertension which could not be controlled either because of (1) drug failures and/or (2) side effects of drugs. Sixteen out of the 26 had had one or more previous episodes of malignant hypertension. Reduced renal function was present in the majority; eight patients were on dialysis. Average preminoxidil blood pressure was 202/127 mm. Hg supine and 162/106 upright which fell to 154/87 supine and 143/86 upright after minoxidil. Propranolol or methyldopa was given to control the reflex increase in heart rate. Edema and congestive heart failure refractory to large doses of potent diuretics necessitated discontinuation of the drug in two patients. Minoxidil proved highly efficacious regardless of initial level of blood pressure, etiology, or supine or upright posture.     

Hypertension, exercise, and beta-adrenergic blockade

STUDY OBJECTIVE: To determine whether beta-adrenergic blocking agents affect exercise tolerance, exercise conditioning response, and blood pressure response to conditioning in hypertensive patients. DESIGN: Randomized, double-blinded, placebo-controlled trial with a 10-week exercise period. SETTING: Outpatient, monitored exercise program at a community-based, university-sponsored cardiac rehabilitation facility. PATIENTS: Thirty adults with mean resting blood pressure of 145 mm Hg or greater (systolic), 95 mm Hg or greater (diastolic), or a combined systolic and diastolic pressure of 140/90 mm Hg or greater. Mean systolic pressure of 170 mm Hg or more or mean diastolic pressure of 105 mm Hg or more was exclusionary. Mean blood pressure was 145/95 mm Hg; mean age was 46.5 years. INTERVENTION: The beta-1-nonselective blocker was propranolol, 80 mg twice daily. The beta-1-selective blocker was metoprolol, 100 mg twice daily, compared with placebo. All patients did exercise conditioning consisting of 40 sessions of aerobic exercise with heart rate monitoring. MEASUREMENTS AND MAIN RESULTS: Resting systolic blood pressure measured without drug therapy was lowered markedly after exercise conditioning on placebo (146 to 135 mm Hg) and on metoprolol (144 to 133 mm Hg) (P less than 0.05), but not on propranolol (no change). Acutely, propranolol decreased both maximal oxygen consumption (VO2max) and exercise duration compared with metoprolol and placebo. Chronically, VO2max increased 24% (95% CI, 8 to 40) in response to training on placebo and 8% on metoprolol (95% CI, 3 to 14); it did not increase on propranolol (95% CI, -10 to 15). CONCLUSIONS: If an exercise program is to be recommended as an adjunct to pharmacologic beta-blockade for hypertension, blood-pressure-lowering effects are preserved and exercise capacity is less affected with a beta-1-selective agent than with a beta-1-nonselective agent. Antihypertensive medications may be avoided altogether for selected patients who sustain an aerobic exercise program.     

A randomized, placebo-controlled, double-blind comparison of amlodipine and atenolol in patients with essential hypertension.

The efficacy and safety of amlodipine (2.5 mg, 5 mg, or 10 mg) once daily was compared with atenolol (50 mg to 100 mg) once daily in patients with mild-to-moderate essential hypertension in a randomized, double-blind, parallel, placebo-controlled study. One hundred and twenty-five patients were randomly allocated at the end of a 4-week run-in placebo period to 8 weeks' double-blind treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The mean changes from baseline in blood pressure 24 h postdose for amlodipine (mean daily dose 8.8 mg) were -12.8/-10.1 mm Hg for supine and -11.5/-9.8 mm Hg for standing blood pressure (P < .001). For atenolol (mean daily dose 83.7 mg) the changes were -11.3/-11.7 mm Hg for supine and -13.3/-12.3 mm Hg for standing blood pressure (P < .001). There were no statistically significant differences between treatments. The responder rates for amlodipine, atenolol, and placebo were 61.1%, 64.9%, and 11.1%, respectively. Determinations taken over the 24-h period at the final visit revealed that amlodipine and atenolol maintained the group mean supine blood pressure at or below 140/90 mm Hg throughout the period of observation; the corresponding time-effect curve for the placebo group was clearly in the hypertensive range. Heart rate was significantly lowered by atenolol only. Both amlodipine and atenolol were well-tolerated. Only one patient was withdrawn because of the development of peripheral edema, arthralgia, and fatigue after treatment with amlodipine. This study demonstrates that once-daily administration of amlodipine or atenolol to mild-to-moderate hypertensive patients was well-tolerated and provided adequate blood pressure control throughout the 24-h dosing interval.     

A comparison of the safety of therapeutically equivalent doses of isradipine and diltiazem for treatment of essential hypertension.

We compared the safety of a new dihydropyridine calcium entry blocker, isradipine, with an equipotent dose of diltiazem in 174 mild hypertensives (diastolic blood pressure [DBP] 95 to 105 mm Hg). After appropriate washout and placebo periods, patients were randomly assigned to receive either 1.25 mg isradipine twice daily (Group I) or 40 mg diltiazem thrice daily (Group D). If DBP remained above 90 mm Hg, doses were increased to a maximum of 5 mg isradipine twice daily or 120 mg diltiazem thrice daily. Active therapy was given for a total of 12 weeks. Only 18 patients (nine from each group) did not complete the protocol. The patients were well-matched at baseline with a mean BP of 149/100 mm Hg for those who were randomized to isradipine and completed the protocol and 153/99 mm Hg for the diltiazem group. The responses to each drug were excellent with 72% of the isradipine patients and 73% of the diltiazem group having DBP less than 90 mm Hg at the completion of the study. Of the 156 patients who completed the protocol, only 18 patients (ten in Group I and eight in Group D) failed to respond. Both drugs were well-tolerated. No adverse reactions were reported by 68 percent of the patients in Group I and 65% of those in Group D. The most common side effect was headache (9.0% in Group I and 7.8% in Group D) followed by fatigue (5.2% in Group I and 3.9% in Group D). Age and race did not predict response to either agent but men responded slightly better to diltiazem than women. We conclude that isradipine and diltiazem are equally well tolerated and can be used successfully as a monotherapy to treat hypertension in a wide variety of patients.     

Rapid blood pressure control with minoxidil: acute and chronic effects on blood pressure, sodium excretion, and the renin-aldosterone system.

Changes in blood pressure, heart rate, electrolyte excretion, and the renin-angiotensin-aldosterone system were monitored before and after minoxidil was added to a regimen of a diuretic and propranolol hydrochloride in 12 severely hypertensive patients. None required more than 40 mg of minoxidil daily for control. On a constant intake, urinary sodium excretion decreased, while urinary potassium excretion remained stable. Heart rate, body weight, and plasma volume increased, while creatinine clearance did not change. Although plasma renin activity increased fourfold, the plasma aldosterone concentration did not increase. Six subjects were restudied after two months of minoxidil treatment. Although blood pressure control continued to be excellent in these subjects, plasma renin values and plasma volume had returned to pretreatment levels. These studies suggest that minoxidil rapidly and effectively lowers blood pressure. Although sodium retention accompanies minoxidil administration acutely, the effect is independent of aldosterone and may be transient.     

Antianginal efficiency of nifedipine with and without a beta-blocker, studied with exercise test. A double-blind, randomized subacute study.

Twenty-one patients, mean age 60.3 years, with stable angina pectoris earlier treated with beta-blockers, were investigated with standardized exercise tests to evaluate the action of nifedipine alone and in combination with a beta-blocker. The first exercise test was performed 3 weeks after treatment with the patient's usual beta-blocker. Following this, the patients were tested twice after a double-blind cross-over 3-week trial with nifedipine and placebo. The patients were subsequently treated for 3 weeks with nifedipine 10 mg 3 times daily or placebo and then performed an exercise test. During the 4th period of 3 weeks the patients took a combination of nifedipine, 10 mg 3 times daily, and their usual beta-blocker and then performed the final exercise test. Nifedipine alone raised the heart rate by 5 beats/min at rest and diminished the systolic blood pressure at rest by 17 mm Hg. During exercise at comparable load the heart rate did not change significantly, but the systolic blood pressure decreased with 22 mm Hg. The exercise tolerance expressed as total work increased on a average by 20%, range-14 - + 194%. Nifedipine in combination with a beta-blocker gave a further decrease in the systolic blood pressure, totally 37 mm Hg at comparable load. The exercise tolerance increased more, totally by an average of 41%. There was a significant correlation between basal values for systolic blood pressure registered during the placebo period at rest and the percentage change in total work. The atrioventricular conduction time did not change significantly compared to placebo during treatment with nifedipine or the combination nifedipine + beta-blocker. No serious side-effects were observed during the study.     

A randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of dual ACE/NEP inhibitor GW660511X in mild-to-moderate hypertensive patients

This multicentre, double-blind, placebo-controlled, parallel-group study determined the efficacy and safety of GW660511 200 mg, a dual inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in mild-to-moderate hypertensive patients (diastolic blood pressure (DBP), > or =90 and < or =109 mm Hg; systolic blood pressure (SBP), > or =150 and < or =180 mm Hg). After a single-blind 2- to 4-week placebo run-in period, 123 patients (aged 18-65 years) were randomized to either placebo (n=62) or to active treatment (n=61) consisting of two consecutive 3-day dose titration periods of GW660511X 50 mg once daily and 100 mg once daily followed by GW660511X 200 mg once daily for 14 days. GW660511X 200 mg significantly lowered (baseline and placebo-corrected) both trough mean cuff SBP (-8.00 mm Hg, P=0.002) and DBP (-5.38 mm Hg, P=0.003). GW660511X 200 mg significantly reduced placebo-corrected mean 24-h and daytime but not night-time ambulatory SBP and DBP. Over the 0-24 h time period following GW660511X 200 mg, there were significant (P<0.001) reductions in serum ACE activity and significant (P<0.001) increases in plasma ANP concentration compared with placebo in terms of both peak and trough effects. In addition, treatment with GW660511X 200 mg significantly (P=0.003) increased (placebo-corrected, 1.52-fold) urinary excretion of cGMP over the 0-24 h interval. Treatment-related adverse events were experienced by 43% of the patients administered GW660511X 200 mg and 44% of those dosed with placebo with headache the most commonly reported. In conclusion, GW660511X 200 mg is an effective antihypertensive in mild-to-moderate hypertensive patients with potent effects on biological markers of ACE and NEP inhibition.     

A double-blind parallel trial to assess the efficacy of doxazosin, atenolol and placebo in patients with mild to moderate systemic hypertension

The antihypertensive and lipid effects of doxazosin and atenolol were compared in a 10-week, double-blind, parallel, placebo-controlled study. The 129 adults enrolled had mild to moderate hypertension (average supine diastolic blood pressures for doxazosin, atenolol and placebo were 100.6, 101.0 and 99.7 mm Hg, respectively). Patients were randomly assigned to treatment with doxazosin, 1 to 16 mg daily, atenolol, 50 to 100 mg daily or placebo. Among 114 patients included in the efficacy analysis, standing blood pressure (systolic/diastolic) changed by -13/-11 mm Hg with doxazosin (n = 37), -12/-12 mm Hg with atenolol (n = 39) and +1/-1 mm Hg with placebo (n = 38). Mean reductions in blood pressure for doxazosin and atenolol were significantly greater than those for placebo (p less than 0.01), although no statistically significant differences between the active agents were noted. Serum lipid measurements were evaluable for 116 patients, and the 38 doxazosin-treated patients in this group experienced reductions in total cholesterol, total triglyceride and very low density lipoprotein cholesterol levels. Both doxazosin and atenolol demonstrated comparable acceptance profiles. Doxazosin is an effective hypotensive agent with beneficial effects on serum lipid levels.     

Effects of diltiazem on serum lipids, exercise performance and blood pressure: randomized, double-blind, placebo-controlled evaluation for systemic hypertension

Treatment of hypertension with diuretics, beta blockers and alpha blockers may be associated with adverse effects on exercise performance, serum lipids and blood chemistries, as well as with orthostatic effects and fluid retention. A randomized, double-blind, placebo-controlled trial of a sustained-release preparation of diltiazem as sole therapy for moderate essential hypertension was conducted. Diltiazem was administered 2 times a day (360 mg/day) to 16 patients and placebo to 14 patients in a 12-week study. Average supine blood pressure with diltiazem therapy fell from 161/100 to 144/87 mm Hg without fluid retention or orthostatic effects. In an open-label study, patients from the placebo and diltiazem groups continued with diltiazem therapy. At an average of over 8 months, supine blood pressure on diltiazem was 147/88 mm Hg, and after withdrawal to single-blind placebo, average supine blood pressure increased to 173/104 mm Hg. All changes were significant compared with baseline and placebo (p less than 0.01). On diltiazem therapy, maximal treadmill exercise was increased by an average of 55 seconds (p less than 0.01), whereas heart rate, blood pressure and double product (heart rate X blood pressure) were reduced at submaximal exercise, and heart rate and double product were reduced at maximal exercise. No changes in serum glucose, potassium or uric acid were found. No adverse effects on serum lipids occurred. Diltiazem treatment was associated with an increase in high-density lipoprotein cholesterol (52 to 60 mg/dl, p less than 0.006) and a decrease in total cholesterol:high-density lipoprotein cholesterol ratio (4.7 to 4.2, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)