ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension.

The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure (SBP) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy. Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits. Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each. The study was a balanced, randomized crossover design with five periods: placebo; angiotensin converting enzyme inhibitors; beta-blocking drugs; calcium-blocking drugs; and thiazide diuretics. Blood pressure (BP) was measured 24 to 26 h after the previous dose. A questionnaire for side effects was administered at each visit. Seventy-four patients entered the study. beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods. There were 9 of 66 patients on P, 9 of 46 on beta-blockers, 4 of 65 on calcium-blocking drugs, 4 of 65 on diuretic, and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects. Decreases in SBP compared to randomized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg. Blood pressure decrease correlated with placebo BP (P < .0005, r = 0.53 to 0.70). When corrected for placebo, target SBP (<140 mm Hg) was reached in between 6% to 15% of patients on monotherapy. Sequential monotherapy achieved target in 29%. Angiotensin converting enzyme inhibitors, calcium-blocking drugs, and diuretics had no more side effects than placebo. Patients on beta-blockers had more side effects and the well-being score was reduced. Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure. beta-Blockers were relatively ineffective, were frequently contraindicated, and had more side effects. Monotherapy achieved control in only a small number of patients. In elderly people with essential hypertension, therapy should be instituted with diuretics or calcium-blocking drugs, but combination therapy will usually be required to achieve goal.

The prevalence of obstructive sleep apnea in hypertensives.

This study was designed to measure the prevalence of obstructive sleep apnea in untreated and treated hypertensive patients by comparing them with normotensive subjects, taking into account the possible confounding variables body mass index, age, sex, and alcohol consumption. Subjects with no known sleep disorders were recruited, had full polysomnography, and had their blood pressure assessed with a 24-h ambulatory monitor. Subjects with a mean 24-h blood pressure greater than 140/90, and receiving no treatment for, or with no history of, hypertension were classified as untreated hypertensives; those receiving antihypertension medication were classified as treated hypertensives; those with a mean 24-h blood pressure less than 140/90 and no history of hypertension were classified as normotensives. Thirty-eight percent of the 34 untreated and 38% of the 34 treated hypertensives, and 4% of the 25 normotensives had apnea-hypopnea indexes greater than 5. Logistic regression analysis showed that body mass index (p = 0.001), age (p = 0.07), sex (p = 0.07), treated hypertension (p = 0.05), and untreated hypertension (p = 0.06) were associated with the presence of sleep apnea, but that alcohol consumption (p = 0.82) was not. It is concluded that there is a relationship between sleep apnea and hypertension that, although partially explained by the confounding variables body mass index, age, and sex, persists when these are allowed for.

Antihypertensive efficacy and safety of perindopril in mild-to-moderate essential hypertension: results of a double-blind multicenter study versus atenolol.

A 3-month double-blind multicenter trial compared the efficacy and safety of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor, with atenolol in mild-to-moderate essential hypertension. A total of 190 patients, 49 of whom were diabetic, entered the perindopril-atenolol comparison. Of these, 163 had been previously treated and had a 4-week run-in period on placebo; 27 had previously been untreated and received placebo for 2 weeks. At entry, all patients who had a supine diastolic blood pressure (DBP) of 95-115 mm Hg were randomized to receive perindopril 2 mg or atenolol 25 mg, once daily. Patients were assessed at 2 weekly intervals for the first month and then monthly for 2 more months. If supine DBP was greater than 90 mm Hg, treatment was increased by stepwise doubling of dose up to 8 mg perindopril or 100 mg atenolol once daily, and later by the addition of hydrochlorothiazide 25 mg, (indapamide 2.5 mg in diabetic patients) once daily. The two groups were homogeneous prior to treatment except for supine and erect heart rate, which were higher in the perindopril group than in the atenolol group (p less than 0.05). Mean supine DBP was 101.1 +/- 0.6 mm Hg in the perindopril group (n = 94) and 99.9 +/- 0.6 mm Hg in the atenolol group (n = 96). After 3 months' active treatment, 74% of patients in the perindopril group achieved a supine DBP of less than or equal to 90 mm Hg and 73% of patients in the atenolol group achieved the same goal. Monotherapy controlled supine DBP in 67% of the perindopril group and 63% of the atenolol group. The decrease in supine DBP was not significantly different between the two groups (-12.9 +/- 0.9 versus -14.7 +/- 0.9 mm Hg) but the decrease in erect DBP was lower in the perindopril group (-10.3 +/- 0.9 versus - 13.4 +/- 1.0 mm Hg, p less than 0.02). Heart rate was reduced in the atenolol group (p less than 0.001). Sixteen patients withdrew from the study; nine were attributed to adverse events, two in the perindopril group and seven, including one death, in the atenolol group. Cough was spontaneously reported by 13% patients of the perindopril group and 1% patients of the atenolol group. In 5% of the perindopril cases this was mild and associated with upper respiratory tract infection. The nature and incidence of other symptoms were similar with both drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Coordinated delivery of clinical care: the "re-integration" of the medical group practice.

This paper suggests that for medical knowledge to be effective, it must be reliably translated into a series of synchronized activities, both clinical and operational. The goal of medical information science must be not only to identify the best course of care, but also through the use of systems for the ordering, scheduling, and deployment of staff and resources to assure that the planned course of care is reliably and efficiently delivered in actual practice settings. We present a brief history of several innovations in patient care coordination and logistics at Mayo Clinic to provide background for the main concepts presented. The principle of patient care coordination underlying this history of innovation is shown to have evolved into a new need for information systems capable of proactively effecting the delivery of care through patient, staff and resource deployment and monitoring.

Pharmacokinetics and concentration--effect relationships of bevantolol (CI-775) in normal volunteers.

The pharmacokinetic handling of the beta 1 selective adrenoceptor blocking drug, bevantolol, was studied in 12 healthy volunteers. After intravenous (i.v.) administration of 50 mg of the drug, there was a biexponential decline in plasma levels with a terminal elimination half life (t1/2) of 1.9 h (range 1.4-2.3 h) and a total apparent volume of distribution at equilibrium of 62 L. After oral administration of the same dose, the bioavailability averaged 57% (range 26-98%) and peak plasma levels varied over a threefold range. On average, less than 1% of the dose was eliminated unchanged in the urine, indicating that the clearance of the drug was accounted for almost entirely by metabolism. Plasma levels after oral dosing with food showed an average 75-min delay in achievement of peak plasma levels and an average 14% increase in the extent of bioavailability of the drug. A positive correlation (r = 0.79) existed between the logarithm of the plasma bevantolol level and the percentage of reduction in postexercise heart rate. A plasma drug level of approximately 200 ng/ml produced a 10% reduction in postexercise heart rate. Pharmacological studies using guinea pig atrial and tracheal tissue demonstrated that the beta-blocking potency and beta-selectivity of bevantolol were intermediate between those of metoprolol and atenolol.

Pharmacokinetic properties of captopril after acute and chronic administration to hypertensive subjects.

The pharmacokinetic properties of captopril were studied in two groups of hypertensive patients; (1) those who had never taken captopril (acute group), and (2) those who had been taking captopril for at least 6 months (chronic group). It was found that after 100 mg of captopril orally, the mean peak plasma level in the chronic group was three times higher than that in the acute group while the area under the curve was twice as high in the chronic group. These data suggest that bioavailability increases with chronic administration, and thus it may be possible to reduce the dosage of captopril and still maintain blood pressure control while reducing side effects.

The lymph nodes of the porta hepatis.

The area under the liver was dissected in 27 human autopsy specimens to search for lymph nodes in the fissures. Nodes were present in all instances. They were in the transverse fissure, posterior to the portal vein, posterior to pars transversus of the left portal vein and associated with the left hepatic artery. The size varied from 2 millimeters to 2 centimeters. Each node was histologically confirmed. Nodes were infrequent and small on the right. Nodes were not found between the portal vein, hepatic artery and bile ducts in the fissures. Nodes were found outside the fissures in the fascia between the bile duct and hepatic artery. Occlusion of the portal vein and hepatic artery could be expected before occlusion of the bile duct. Node enlargement in the transverse fissure is anticipated as a rare cause of jaundice.