Patient selection and the assessment of blood pressure in clinical trials

A new method for selecting patients with mild-to-moderate hypertension who are appropriate for entry into clinical trials and a technique for assessing small but statistically significant decreases in diastolic blood pressure resulting from drug therapy are described. In this method, mild-to-moderate hypertension is defined to exclude subjects whose diastolic blood pressure decreases while they are taking placebo and to exclude subjects with highly variable diastolic blood pressure. A subject receives placebo for four weeks, during which time diastolic blood pressure while supine is measured three times on a single day of each week, the time between measurements not being less than 30 minutes. With the 12 measurements obtained during the four-week placebo period, the following calculations are made: an average of the 12 measurements; and average of the three measurements obtained on a given day, yielding the average diastolic blood pressure per week; and the range of the 12 measurements. Subjects are selected for study if their average diastolic blood pressure per week for the four-week placebo period is neither below 95 nor above 115 mmHg, if their average diastolic blood pressure per week does not decrease successively from week 1 to week 4, and if the range of the 12 measurements of diastolic blood pressure recorded over the four-week placebo period does not exceed 28 mmHg (equivalent to a standard deviation of 8.5). Use of the method is demonstrated in the selection of 63 patients for a double-blind study of two antihypertensive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ambulatory blood pressure monitoring: an argument for wider clinical use

Ambulatory blood pressure monitoring predicts cardiovascular risk better than office readings do. It can detect white-coat hypertension, masked hypertension, and normal and aberrant patterns of circadian variation in blood pressure. Though the clinical role of ambulatory blood pressure monitoring is currently limited, its use can be considered in many common clinical situations, eg, resistant hypertension, transplantation, pregnancy, chronic kidney disease, and dialysis. It may help in therapeutic decision-making and save money in the long term.     

Evidence from large clinical trials for Japanese hypertensive patients

Large-scale clinical trials for the hypertensive patients have been carried out in Japan. Double-blind, placebo-controlled large clinical trials in Europe and USA showed that antihypertensive drugs prevented cardiovascular disease. Recently large clinical trials carried out in Japan. These clinical trials have shown that the onset rate of the heart vascular disease in Japanese hypertensive patients, the factor which influenced the onset of the cardiovascular disease, and the suppressant effect of cardiovascular disease of different antihypertensive drug class.     

Ambulatory blood pressure monitoring in daily clinical practice – the Spanish ABPM Registry experience

Many patients are hypertensive at the medical settings but show normal blood pressure out of the doctor's office, and are classified as white‐coat hypertensives. On the other hand, many patients with controlled hypertension at the clinic show ambulatory blood pressure levels above the thresholds considered for an adequate blood pressure control, known as having masked hypertension. Using data from the Spanish Ambulatory Blood Pressure Monitoring Registry (Spanish ABPM Registry), a national program developed to promote the use of the ambulatory technique for hypertension management in daily practice, we have reviewed the main strengths of this approach, that is the ability to detect discrepancies of blood pressure status with respect to office blood pressure measurement, and to better assess accurate rates of hypertension control. White‐coat hypertension within patients with elevated office blood pressure, and masked hypertension within office‐controlled patients affected one of three patients in each office status. On the other hand, rates of ambulatory blood pressure control (50%) doubled those of office blood pressure control (25%), still remaining half the patients uncontrolled. We think that a systematic use of ambulatory blood pressure monitoring, and strategies to improve blood pressure control constitute key priorities in hypertension management.     

Monitoring versus interim analysis of clinical trials: a perspective from the pharmaceutical industry

The definitions of "interim analysis" and "monitoring" of clinical trials are often ambiguous in the current literature. The resulting confusion can lead to erroneous conclusions and misguided decisions, especially when activities that are operational or observational are evaluated in a probabilistic sense as inferential. The authors seek to define "interim analysis" and "monitoring" in a mutually exclusive fashion. These definitions will then provide the opportunity to review and categorize existing clinical trial practices and procedures. This will clarify such issues as "when to look" and "when to pay a price" (e.g., test size and power) and characterize such issues in the context of pharmaceutical industry drug development.     

The impact of automated blood pressure devices on the efficiency of clinical trials.

By reducing measurement error, automated blood pressure (BP) devices should enhance the precision of BP estimation and thereby decrease sample size requirements in clinical trials of BP-lowering therapy. Enhanced precision would be particularly relevant to clinical trials assessing the efficacy of nonpharmacological therapies. In the present investigation, resting (clinic) BPs by the Dinamap 8100 (a stationary device) and the Accutracker II (an ambulatory device) were as precise as manual BPs given an equal number of observations by each method. However, both the Dinamap and Accutracker devices underestimated resting diastolic BP in comparison to the manual observers. Estimates of average daytime and 24-hour ambulatory BP, based on large numbers of observations over an extended period of time, were extremely precise. These findings suggest that the use of automated devices to measure resting BP may not reduce samples sizes, whereas use of ambulatory BP devices should reduce samples sizes considerably.     

Ambulatory blood pressure monitoring and prognosis in the management of essential hypertension

Over the past decade, several prospective outcome studies have demonstrated that ambulatory blood pressure measurements provide a better prediction of major cardiovascular events compared with clinic blood pressure measurements. This review summarizes the advantages of ambulatory blood pressure over clinic blood pressure to predict outcome in untreated and treated hypertensive subjects. Based on available evidence, an operational flow-chart in order to interpret results of ambulatory blood pressure for a better management of these subjects is suggested.     

Ambulatory blood pressure monitoring and prognosis in the management of essential hypertension

Over the past decade, several prospective outcome studies have demonstrated that ambulatory blood pressure measurements provide a better prediction of major cardiovascular events compared with clinic blood pressure measurements. This review summarizes the advantages of ambulatory blood pressure over clinic blood pressure to predict outcome in untreated and treated hypertensive subjects. Based on available evidence, an operational flow-chart in order to interpret results of ambulatory blood pressure for a better management of these subjects is suggested.     

Ambulatory blood pressure monitoring. Values in normotensive patients and suggestions for interpretation

We performed 24 hours ambulatory blood pressure monitoring with non invasive devices in 233 normotensive patients during a workday. Their age ranged from 21 to 74 years (mean +/- standard deviation = 39 +/- 11, 37% females). These patients were mainly recruited on their workplace. Blood pressure monitoring was proposed to all volunteers without any history of hypertension, independently of the casual blood pressure measured by a doctor after 10 minutes sitting, just before monitoring. Patients were asked to note precisely their bedtime and the moment of getting up and to start a blood pressure measurement as getting up. This measure was used as the starting point of the 24 hours blood pressure curve for each patient. Pooling all patients in that way shows an important rise of blood pressure as standing up but no significant variation before. So we calculated the average blood pressure during the true time of activity and of bedrest for each block of 10 years from 20 to 60 years, separately for men and women. These values may be used as a guide when interpreting 24 hours blood pressure recordings.     

Guidelines for the management of hypertensive crises and simple blood pressure rise. Literature review and clinical experience

Hypertension is a common clinical problem in the Emergency Department. Beside homologated therapeutical approaches it is necessary in primis to consider the problem in a clinical context and in an appropriate nosographic scheme in order to provide a rational approach to the treatment. In this paper the authors review the nosographic and therapeutical approaches previously reported in literature and then state their proposals derived by their daily experience at the Emergency Department. In authors' opinion it is of primary importance to distinguish between hypertensive crises and simple blood pressure rise. For this end it seems useful to define four syndromic classes: A. Real Hypertensive Crises: 1-Hypertensive Emergencies, 2-Hypertensive Urgencies. B. Simple Blood Pressure Rise: 1-Stable Uncomplicated Hypertension, 2-Transient Hypertension. According to this classification the majority of patients referring to Emergencies Departments for elevated blood pressure can be included in the last two classes. The authors suggest a step-by-step approach to the treatment beginning with benzodiazepines, loop diuretics, beta-blockers or clonidine or ACE inhibitors or calcium channel blockers; In an elevated percentage of cases benzodiazepines alone are effective in appropriately lowering blood pressure.     

Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials

Data from seven randomized, placebo-controlled, double-blind phase III clinical trials were analysed to further evaluate the efficacy of rizatriptan 10 mg (n = 2068) in comparison with placebo (n = 1260) and rizatriptan 5 mg (n = 1486) for the acute treatment of a migraine attack. Migraine was diagnosed according to International Headache Society criteria. Headache severity, associated migraine symptoms and functional disability were measured immediately before dosing and at 0.5, 1, 1.5 and 2 h. Headache recurrence (return of moderate or severe headache after an initial response) was also recorded. In addition to conventional pain relief (reduction of moderate or severe headache to mild or none) and pain free measures, the analysis looked at the elimination of associated migraine symptoms and disability in patients who had symptoms or disability at baseline. Maintenance of pain relief or pain-free status over 24 h was also analysed. At 2 h, rizatriptan 10 mg was significantly more effective than placebo for pain relief (71% vs. 38%, P < 0.001), and for elimination of pain, nausea, photophobia, phonophobia and functional disability. The benefit was maintained over 24 h; 37% of patients on rizatriptan 10 mg had sustained pain relief vs. 18% for placebo (P < 0.001). Rizatriptan 10 mg was also more effective than rizatriptan 5 mg, with a significant superiority at 2 h on all measures except for elimination of nausea. The benefit was maintained over 24 h; 38% of patients on rizatriptan 10 mg had sustained pain relief vs. 32% for rizatriptan 5 mg (P = 0.001).