Appropriate Blood Pressure Control in NIDDM (ABCD) Trial. The effect of how outcomes are framed on decisions about whether to take antihypertensive medication: a randomized trial. A randomized trial of special packaging of antihypertensive medications. Antihypertensive effectiveness of low-dose lisinopril-hydrochlorothiazide combination. A large multicenter study. Lisinopril-Hydrochlorothiazide Group. [Effect of moderate salt restriction on the antihypertensive action of nifedipine: a double blind study]. Prospective study on the treatment of mild hypertension in the aged. Antihypertensive efficacy of alpha-methyldopa, chlorothiazide and Supres-150 (alpha-methyldopa-chlorothiazide). Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring. Adjunctive effect of salt restriction on antihypertensive efficacy.
The ABCD (Appropriate Blood Pressure Control in Diabetes) Trial is a large, prospective, randomized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus (NIDDM) designed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in NIDDM. The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and an angiotensin-converting-enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations aged 40-74 years, 470 hypertensive patients (diastolic blood pressure of > or = 90.0 mmHg at time of randomization) and 480 normotensive patients (diastolic blood pressure of 80.0 mmHg at time of randomization). The study duration is 5 years and is scheduled to end in May of 1998. Patients are randomized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy. Patients are also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control is necessary. The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance. Secondary outcome measures are urinary albumin excretion, left ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity and mortality will also be evaluated. Given the data showing the impact of hypertension on complications in NIDDM, the ABCD Trial is designed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM. We conducted an Internet-based randomized trial comparing three valence framing presentations of the benefits of antihypertensive medication in preventing cardiovascular disease (CVD) for people with newly diagnosed hypertension to determine which framing presentation resulted in choices most consistent with participants' values.
                In this second in a series of televised trials in cooperation with the Norwegian Broadcasting Company, adult volunteers rated the relative importance of the consequences of taking antihypertensive medication using visual analogue scales (VAS). Participants viewed information (or no information) to which they were randomized and decided whether or not to take medication. We compared positive framing over 10 years (the number escaping CVD per 1000); negative framing over 10 years (the number that will have CVD) and negative framing per year over 10 years of the effects of antihypertensive medication on the 10-year risk for CVD for a 40 year-old man with newly diagnosed hypertension without other risk factors. Finally, all participants were shown all presentations and detailed patient information about hypertension and were asked to decide again. We calculated a relative importance score (RIS) by subtracting the VAS-scores for the undesirable consequences of antihypertensive medication from the VAS-score for the benefit of CVD risk reduction. We used logistic regression to determine the association between participants' RIS and their choice. 1,528 participants completed the study. The statistically significant differences between the groups in the likelihood of choosing to take antihypertensive medication in relation to different values (RIS) increased as the RIS increased. Positively framed information lead to decisions most consistent with those made by everyone for the second, more fully informed decision. There was a statistically significant decrease in deciding to take antihypertensives on the second decision, both within groups and overall.
                For decisions about taking antihypertensive medication for people with a relatively low baseline risk of CVD (70 per 1000 over 10 years), both positive and negative framing resulted in significantly more people deciding to take medication compared to what participants decided after being shown all three of the presentations.
                International Standard Randomised Controlled Trial Number Register ISRCTN 33771631. This article reports a randomized controlled trial designed to test the effects of special packaging of antihypertensive medication on compliance and blood pressure control. One hundred eighty subjects who had exhibited elevated blood pressure greater than 90 mmHg in the two years prior to the study were recruited from patients receiving care at a community hospital-based family medicine practice. After completing preenrollment interviews and blood pressure measurements, subjects were randomly assigned to receive their antihypertensive medications either in the usual vials or in special unit dose-reminder packaging. Follow-up interviews, pill counts, and blood pressure measurements were performed at three-month intervals. There were no statistically significant differences between the control and experimental groups with regard to age, sex, race, employment, education, marital status, insurance coverage, or blood pressure regimens. Prior to the intervention, the experimental group had slightly lower diastolic blood pressure and reported better compliance than the control group. Analyses performed on 165 subjects completing the first follow-up visit revealed no significant improvements in blood pressure control or compliance for patients receiving special medication packaging. While some patients found it easy to remember to take pills packaged using this format, they also found the packages somewhat more difficult and inconvenient to use. In contrast to previously reported work, this study did not demonstrate any significant improvement in compliance with special packaging of antihypertensive medications. To test the antihypertensive and metabolic effects of lisinopril, 10 mg/d (L); hydrochlorothiazide, 12.5 and 25 mg/d (H12.5 and H25); and its combination with lisinopril (L/H12.5 and L/H25) against placebo in patients with mild to moderate (stage I and stage II) hypertension.
                Multicenter, double-blind, placebo-controlled outpatient study of 12 weeks' duration.
                After 4 weeks of single-blind placebo treatment, 505 patients whose sitting diastolic blood pressure was 100 to 114 mm Hg were randomized into the study--467 patients completed it (placebo, 71; L, 80; H12.5, 79; H25, 77; L/H12.5, 79; and L/H25, 81). The patients were seen in the clinic every 2 weeks, where measurements of their sitting and upright blood pressure and heart rate were taken 24 +/- 2 hours after drug administration. Complete blood cell counts with differential cell counts, blood chemistry studies, urinalyses, and electrocardiograms were done at baseline and during the study. Roentgenograms were done once at baseline.
                Compared with placebo, all drug regimens decreased sitting and upright blood pressure (P < .001) and had no effect on sitting and upright heart rate. The greatest effect was obtained with the combinations of L/H12.5 and L/H25. There was no difference between L/H12.5 and L/H25 or between H12.5 and H25. There were no serious clinical side effects except cough, which was slightly higher with L, L/H12.5, and L/H25. The only metabolic side effects were in serum potassium level, which was lower with H25 (P < .01), and serum glucose level, which was higher with H25 and L/H25 (P < .01).
                The data suggest that (1) monotherapy of hypertension with L, H12.5, H25, L/H12.5, and L/H25 was effective and well tolerated; (2) the best results were achieved with L/H12.5 and L/H25; (3) lower doses of hydrochlorothiazide either alone or in combination with lisinopril were equipotent with higher doses and were free of metabolic side effects. Moderate salt restriction is of debatable efficacy in the treatment of mild or moderate hypertension; however, salt restriction enhances the activity of most antihypertensive drugs. Some observations suggest that the antihypertensive activity of calcium antagonists is not increased or could even decrease with dietary salt restriction. In the present work 15 patients suffering arterial hypertension and normal renal function are studied during four two week periods; a) unrestricted diet and medication, b) unrestricted diet and nifedipine (40 mg/day), c) low salt diet (5 g of salt/day) and nifedipine, and d) the same low salt diet, nifedipine and a salt supplement (6 g/day); salt or placebo were given in a double blind manner. At the end of each period arterial blood pressure was recorded, a urine sample for sodium determination was taken, and a blood sample was drawn for serum renine activity and biochemical parameters; at the end of each period patients' weight was recorded. Blood pressure significantly decreased (systolic: 9.83%, and dyastolic 11.17%) in patients treated with nifedipine, with no differences observed with salt modifications. Urinary sodium reflected correctly dietary salt modifications. Serum renine activity significantly increased during salt restriction. No significant changes were observed in weight or in the biochemical parameters studied. These results seem to suggest that the antihypertensive effect of nifedipine in patents suffering mild to moderate essential hypertension, with no change observed is not altered by the amount of salt in diet, at least within the limits studied (89.7 to 190 mEq/day of Sodium). The 4 year prospective trial on the effectiveness of the antihypertensive treatment was performed in 100 mild hypertensive patients of the aged, the average age being 76.1 years. Dropouts during the drug-off control period were 9 cases. The matched pair group was selected by the age, sex, and blood pressure. Forty-four drug treated cases and 47 placebo treated cases were comparable in blood pressure as well as in laboratory data. Cerebrovascular and cardiac complications were observed in 4 cases or 10.5% in the drug group, and in 9 cases or 22.0% in the placebo group. When 8 cases of blood pressure elevation over 200/110 mmHg in the placebo group were added to the cardiovascular complications, dropouts in placebo group reached 41.5%, and this showed the significant difference. Other complications were observed in 12 cases or 31.6% in the drug group and in 17 cases or 41.5% in the placebo group. Major complications were cancers, infections, and bone or joint diseases. Blood pressure was decreased from 171/87 to 151/80 in the drug group, and the average decrease was 20/7 mmHg in 4 year period. No significant changes in hematocrit, serum protein, urea nitrogen, uric acid, sodium, and potassium were observed during the trial period. The present study suggested that antihypertensive treatment was effective in the aged with mild hypertension, and that careful follow up was needed not only for cardiovascular complications but also for general health condition. Twenty-two white men and two white women with uncomplicated essential hypertension participated in a randomized double-blind trial comparing placebo with alpha-methyldopa (750 mg/d orally) and chlorothiazide (450 mg/d orally), alone or in combination. There were no significant differences in blood pressures as measured with the patients lying down; however, with the patients standing the systolic, diastolic and mean arterial blood pressures were significantly lower (P < 0.05) after treatment with alpha-methyldopa or the combination product. The higher the blood pressure before treatment, the greater the fall with treatment. Adverse effects were infrequent. To evaluate patterns of compliance with once versus twice daily administration of antihypertensive therapy (primary-outcome measure) and relevance of partial compliance for blood pressure control (secondary outcome measure).
                Multicentre, nonblinded, parallel group randomized design.
                Nonacademic primary care practices across Canada.
                Patients with mild essential hypertension (diastolic blood pressure 95 to 110 mmHg) of either sex (40% women), age 18 to 80 years (average 55 years). One hundred and ninety-eight patients were randomized to active treatment; 14 patients discontinued the study because of side effects.
                After a four-week placebo run-in period, patients were randomized to amlodipine 5 mg once-a-day or diltiazem slow release formulation (SR) 90 mg twice daily. Doses were increased to 10 mg and 180 mg to achieve sitting diastolic blood pressure of 90 mmHg or less.
                During 20 weeks on active treatment, compliance was assessed by pill counts and medication event monitoring system (MEMS), assessing percentage of prescribed doses taken, percentage days correct doses taken, percentage prescribed doses taken on time and blood pressure control as determined by office blood pressure measurement.
                The percentage prescribed doses taken (by either pill count of MEMS) showed a high degree of compliance, similar for the two treatments. However, other parameters of compliance were significantly better with once versus twice daily therapy. Partial compliance (less than 80% by pill count) led to less blood pressure control with the short acting diltiazem, but did not affect blood pressure control for the long acting amlodipine. Side effects profiles did not differ between the two treatments.
                Within the constraints of a clinical trial, hypertensive patients in primary care show a high degree of overall compliance with once or twice daily pill-taking, but patterns of pill-taking are more erratic with twice versus once daily medication, particularly in men. The results suggest that the negative consequences of partial compliance for blood pressure control can be offset by choosing agents with a duration of action well beyond the dosing interval. The effect of dietary salt restriction on blood pressure was measured in patients with moderate hypertension receiving antihypertensive medication. Patients were studied during a randomly allocated 6 week period of moderate dietary salt restriction and during a 6 week period of normal diet. Twenty-four of twenty-eight patients achieved a reduction of salt excretion exceeding 20%. In these patients mean urinary sodium excretion fell from 169 (s.e.m. = 13) mmol/24 h to 92 (s.e.m. = 7) mmol/24 h. Potassium excretion and body weight did not change, and with the exception of the erect systolic pressure, there was no overall change in blood pressure. When the data were grouped according to the patient medication, mean supine systolic pressure fell from 148.9 (s.e.m. = 4.4) to 140.3 (s.e.m. = 5.0) mmHg (n = 14, P greater than 0.05) and mean supine diastolic pressure fell from 100.8 (s.e.m. = 2.9) to 97.0 (s.e.m. = 2.8) mmHg (n = 14, P greater than 0.05) in patients taking diuretics. Blood pressure did not change in patients whose medication did not include diuretics. Moderate dietary salt restriction may be therapeutically useful in patients with moderate hypertension treated with diuretics but is of little value in those not receiving diuretics.
Until better evidence is available, the choice of antihypertensive should depend on the clinician's experience and familiarity with a particular drug, and on what is known about adverse effects. Exceptions are diazoxide, ketanserin, nimodipine and magnesium sulphate, which are probably best avoided.
[Note: The 37 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]