Treatment of Severe Hypertension with Atenolol and Betaxolol with Once-Daily Regimens  Hemodynamic Aspects: ResultsThe baseline clinical characteristics of the two groups of patients are listed in Table 1. The patients were male, predominantly white, and there were no significant differences with respect to age, weight, arterial pressure, and heart rate, both supine and upright, between the two groups.
Antihypertensive Effects
The addition of atenolol or betaxolol to diuretic baseline therapy resulted in significant and similar decreases in arterial pressure (p<.001) by both clinic visits and ambulatory measurements (Tables 2 and 3, Fig 1 to 4), and this effect was further enhanced with the addition of the vasodilator. In addition to lowering the arterial pressure, both atenolol and betaxolol significantly decreased the heart rate (p<.001), and the addition of the vasodilator had no appreciable effect (Tables 2 and 3). read more

Hemodynamic and Spirometric Effects
Although the arterial pressure was well controlled in all patients, both drug regimens caused a significant increase in cardiac size observed by both radiographic and echocardiographic measurements (Table 4). The CT ratios, LVIDd, and RVIDd were significantly increased at the end of the study compared with their baseline values (p<.05, P<.01). In contrast, the IVS thickness was decreased (p<.05), and there were no changes in the LVPW thickness or in the left ventricular mass. More important, there was no compromise in the myocardial function, as both the myocardial fiber shortening and the ejection fraction of the left ventricle were not affected by the treatment. Also, no adverse respiratory effects were noted with the addition of p-blockers, as the FEVi, FVC, and FEV/FVC did not change from baseline (Table 4).

Clinical and Metabolic Effects
Besides the 40 patients who completed the study, eight additional patients dropped out of the study for various reasons: six for poor compliance and two for serious adverse effects. One patient in the atenolol group had impotence and severe, difficult to treat edema, and another patient in the betaxolol group had nervousness, insomnia, and weakness. The most common side effects were hypertrichosis, weight gain, and peripheral edema. There was no evidence of pericardial effusion either at baseline or at the end of treatment. The nonsignificant increase in weight at the end of the study is misleading, because edema and weight gain from sodium and water retention between visits was a major problem in the minoxidil-treated patients. This is reflected by the increase in the dose of furosemide from a mean of 40 mg/day at baseline to a mean of 82 ± 10 mg/day at the end of week 16 in the atenolol group and from a mean of 40 mg/day to a mean of 87 ± 10 mg/day in the betaxolol group. The mean daily dose for minoxidil was 12 ± 1 mg and 11 ± 1 mg in the atenolol and betaxolol groups, respectively. The mean daily doses for atenolol and betaxolol were 83 ± 8 mg and 23 ± 2 mg, respectively. With respect to the metabolic side effects, there were no serious adverse hematologic, hepatic, or renal effects noted with the use of these drugs. The most pertinent metabolic findings are listed in Table 5. The favorable changes in plasma lipids, reflected by decreases in total and low-density lipoprotein (LDL) cholesterol and no change in high-density lipoprotein (HDL) cholesterol and triglycerides, are most likely incidental and of no clinical significance.
Table 2—Arterial Pressure Changes with the Addition cf Atenolol and Minoxidil to the Diuretic (Mean±SEM)

Measurement Study Weeks
W4 W6 W8 W10 W12 W14 W16 W20 W24 W28 W32
SSAP, mm Hg 177 ±6 162 ±5* 157 ±5* 153 ±4* 148 ±4* 147 ±4* 143 ±4* 146 ±4* 143 ±3* 144 ±4* 142 ±3*
SDAP, mm Hg 115 ±2* 102 ±2* 98 ±2* 95 ±3* 90± 1* 91 ±2* 90 ±2* 87 ±2* 88 ±2* 87 ±2* 88 ±2*
USAP, mm Hg 170 ±6 160 ±5* 154 ±5* 150 ±5* 145 ±4* 148 ±4* 142 ±4* 143 ±5* 139 ±4* 136 ±3* 133 ±2*
UDAP, mm Hg 116±2 107 ±3* 102 ±2* 98 ±3* 93 ±2* 95 ±2* 93 ±2* 91 ±2* 90 ±2* 91 ±2* 91 ±2*
SHR, bpm 82 ±2 73 ±2* 73 ±2* 72 ±2* 74 ±2* 73 ±2* 70 ±2* 72 ±2* 74 ±2* 72 ±2* 71 ±2*
UHR, bpm 92±2 80 ±2* 81 ±3* 80 ±2* 80 ±2* 79 ±2* 77 ±2* 79 ±2* 81 ±3* 80 ±2* 79 ±2*

Table 3—Arterial Pressure Changes with the Addition qfBetaxolol and Minoxidil to the Diuretic (Mean±SEM)

Measurement Study Weeks
W4 W6 W8 W10 W12 W14 W16 W20 W24 W28 W32
SSAP, mm Hg 170 ±4 152 ±4* 147 ±3* 143 ±3* 138 ±3* 137 ±2* 140 ±3* 137 ±3* 137 ±2* 138 ±3* 136 ±2*
SDAP, mm Hg 114 ±2 100 ±2* 95 ±2* 93 ±2* 88 ±2* 87 ±1* 87 ±2* 87 ±1* 85±1* 86 ±2* 86± 1*
USAP, mm Hg 166 ±4 146 ±4* 141 ±3* 137 ±4* 135 ±3* 133 ±2* 135 ±3* 131 ±2* 130 ±2* 136 ±3* 133 ±2*
UDAP, mm Hg 114 ±2 102 ±2* 97 ±2* 93 ±2* 91 ±2* 90 ±2* 89 ±2* 88 ± 1* 87 ±2* 89 ± 1* 89 ±1*
SHR, bpm 80±2 66 ±2* 68 ±2* 67 ±2* 67 ±2* 68 ±2* 65 ±2* 65 ±2* 69 ±2* 67 ±2* 67 ±2*
UHR, bpm 90±3 73 ±3* 74 ±2* 73 ±2* 74 ±2* 74 ±2* 70 ±2* 72 ±2* 75 ±2* 73 ±2* 72 ±2*

Table 4—Hemodynamic and Spirometric Effects of Atenolol and Betaxolol in Triple Therapy of Severe Hypertension (Mean ± SEM)

Atenolol Betaxolol
Measurement Before After Before After
CT ratio, % 46.8 ± 1.7 49.3 ± 1.8t 47.8 ±1 50.7 ± It
LVIDd, mm 46 ± 1 51 ±2| 49 ±2 55±2t
RVIDd, mm 20.3± 1.1 22.8± 1.4* 19.3± 1.3 22.2 ± 1.3*
IVS, mm 13.4 ±.8 12.1 ±.9* 14.7 ± .6 12.9± .7*
LVPW, mm 12.3 ±.8 11.8± .8 11.3± .5 11.9± .5
LVM, g 262 ±18 270 ±41 282 ±21 295 ±31
EF, % 69 ±2 73 ±2 70 ±2 69 ±3
FEV„ 1 2.7 + 0.4 2.7±0.3 2.5±0.2 2.5±0.2
FVC, 1 3.5 ±0.4 3.4 ±0.4 3.5±0.2 3.4 ±0.2
FEV„ FVC 0.75 ±0.05 0.77 ±0.05 0.70 ±0.03 0.73 ±0.03

Table 5—Metabolic Effects of Atenolol and Betaxolol in Combination with Furosemide and Minoxidil

Atenolol Betaxolol
Measurement Before After Before After
Weight, lb 205 ±9 210 ±8 209 ±7 215 ±5
Creatinine, mg/dl 1.1 ± .1 1.2 ± .1 l.l±.l 1.2 ± .1
BUN, mg/dl 15 ± 1 18 ±2 15 ± 1 18 ±1*
Glucose, mg/dl 107 ±6 116 ±10 112 ±9 115 ±11
Cholesterol, mg/dl 241 ±7 215 ±9t 250 ±12 234 ± 10t
LDL, mg/dl 154 ±7 132 ±9t 152 ±9 146 ±9*
HDL, mg/dl 40±3 43±3 43±2 42±2
Triglycerides, mg/dl 223 ±31 225 ±28 242 ±30 236 ±31
K+, mEq/L 4.0±0.1 3.6±0.1t 4.1 ±0.1 3.9±0.1
Ca+ + , mg/dl 9.7± .1 9.7± .1 9.7± .1 9.6± .1
MG+ + , mEq/L 1.86±0.04 1.91 ±0.04 1.80 ±0.03 1.82 ±0.04

 

Figures 1 and 2. Mean changes from baseline in the supine and standing arterial pressure. The drug regimens were equipotent in reducing the arterial pressure. ATE = atenolol; BETA = betaxolol.

Figures 1 and 2. Mean changes from baseline in the supine and standing arterial pressure. The drug regimens were equipotent in reducing the arterial pressure. ATE = atenolol; BETA = betaxolol.

Figures 3 and 4. Ambulatory pressures (mean±SEM) of patients treated with furosemide alone and in combination with either atenolol or betaxolol. Comparisons were made between 8 am and 8 am of next day. DIU = diuretic; ATE = atenolol; BETA = betaxolol.

Figures 3 and 4. Ambulatory pressures (mean±SEM) of patients treated with furosemide alone and in combination with either atenolol or betaxolol. Comparisons were made between 8 am and 8 am of next day. DIU = diuretic; ATE = atenolol; BETA = betaxolol.