Recent clinical trials in hypertension suggest that thiazide diuretics may increase coronary heart deaths in selected patients, possibly through adverse effects on serum potassium, lipids, lipoproteins, and/or apolipoproteins. Administration of smaller doses of diuretics has been recommended to decrease this risk. We evaluated 12.5-mg and 112.5-mg daily doses of hydrochlorothiazide (HCTZ) administered for 1 month to nine postmenopausal black female hypertensives using a double-blind, randomized, crossover design. Both regimens produced significant reductions in sitting diastolic blood pressure, a mean of 11 mm Hg with the high dose and 8 mm Hg with the low dose. The high dose produced a mean 0.7 mEq/L reduction in serum potassium while the low dose caused no change. Both doses produced similar changes in serum lipoproteins. Statistically significant elevations were seen in total cholesterol (approximately 12%), LDL cholesterol (approximately 20%), cholesterol: HDL ratio (approximately 15%), and apolipoprotein B (approximately 20%). Apolipoprotein A1 was significantly reduced (approximately 6%). These results support the use of low doses of HCTZ in mild hypertension to avoid hypokalemia, but suggest that adverse changes in serum lipids will occur.
The nonsteroidal antiinflammatory drug (NSAID) indomethacin has been shown to increase blood pressure in normotensive individuals. The effect of other NSAID on blood pressure has not been as well studied. We evaluated the effects of ibuprofen, an NSAID currently available without a prescription, on 24-hour ambulatory blood pressure in ten young, healthy, normotensive women. Using a randomized, crossover, double-blind design, subjects received ibuprofen 800 mg and a placebo identical in appearance to ibuprofen three times a day for eight days with a washout period between regimens. Subjects were instructed to follow a no-added salt diet during the study. Twenty-four-hour blood pressure monitoring and 24-hour urine collection for prostaglandin E2, creatinine, and sodium were performed on days 1 and 8 of each study week. Tablet counts and a 40 percent reduction in urinary prostaglandin E2 documented compliance with ibuprofen. Ibuprofen had no significant effect on systolic or diastolic blood pressure at any hour during the 24-hour period. Mean blood pressure for the 24-hour period was 112/73 and 111/73 mm Hg on day 1 and 111/73 and 112/73 mm Hg on day 8 for placebo and ibuprofen, respectively. We conclude that ibuprofen at doses as high as 2400 mg/d for up to seven days has no effect on blood pressure in normotensive women. Further studies are needed in hypertensive subjects.
The purpose of this multicenter investigation was to determine the efficacy and safety of the alpha/beta-blocker labetalol versus the beta 1-selective beta-blocker atenolol in white and black patients with essential hypertension. Equal numbers of black and white patients were enlisted to form four treatment groups (white patients taking either labetalol or atenolol and black patients taking either labetalol or atenolol). Two hundred ninety-two patients (152 white and 140 black patients) with essential hypertension characterized by a standing diastolic blood pressure of 105 to 119 mm Hg (inclusive) were recruited for this trial. Patients were randomized to either labetalol (dosage titrated from 200 to 1600 mg/day) or atenolol (dosage titrated from 50 to 100 mg/day). The therapeutic goal was achievement of a standing diastolic blood pressure of 90 mm Hg or less or a fall of 15 mm Hg in diastolic pressure from baseline value at the end of the placebo run in period. At the end of the study there were no significant differences in blood pressure or heart rate changes in the supine position between the labetalol and atenolol groups. In contrast, labetalol produced greater reduction in both the standing systolic and diastolic blood pressure (-12/-13 mm Hg, respectively) compared with atenolol (-7/-9 mm Hg; p less than 0.05; p less than 0.005, respectively). The greatest decrease in blood pressure was observed in white patients receiving labetalol. In black patients the decrease in blood pressure was greater in those treated with labetalol compared with atenolol, particularly with respect to the systolic blood pressure. We conclude that the alpha 1-blocking property of labetalol provides an additional lowering of the blood pressure over that seen with beta 1-blockade alone, especially in the standing position, and this enhanced efficacy is not confined to one radical group.
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