Risk assessment and treatment benefit in intensively treated hypertensive patients of the Hypertension Optimal Treatment (HOT) study

BACKGROUND: The Hypertension Optimal Treatment (HOT) Study provided information about cardiovascular events in 18,790 hypertensives, subjected to pronounced blood pressure lowering for a mean of 3.8 years. METHODS AND RESULTS: The HOT Study data have been further analysed after risk stratification of the patients (1999 World Health Organization and International Society of Hypertension guidelines criteria): (i) no patients of the HOT Study were classified as low risk, 50% were classified as medium risk, 20.2% as high risk and 29.8% as very high risk; (ii) incidence of cardiovascular events in these patients with excellent blood pressure control [92% had diastolic blood pressure (DBP) < or = 90 mmHg] remained proportional to pretreatment risk. The relative risk of very high- versus medium-risk strata was between two and three both when HOT Study patients were considered independently of, or within the DBP target group they had been randomized to; and (iii) event rates in all risk strata were calculated to be much lower (possibly 60% lower) than rates expected from baseline risk calculated approximately by the Framingham equation. CONCLUSIONS: The low event rate in HOT Study patients is likely to result from pronounced blood pressure lowering, and is not explained by a lower risk profile than in previous controlled trials of antihypertensive treatment. The persistence of a risk gradient despite intensive blood pressure lowering suggests a combination of blood pressure control with other strategies of risk correction and the need to initiate antihypertensive therapy before complications develop

Klinische Pharmakologie als kooperative Aufgabe Schlussbericht

Knowledge of clinical pharmacology gained from pertinent research provides an important basis for appropriate drug therapy 1990, the German Research Council in their review of academic institutions stated a deficit in this subject area. As a consequence, the German Federal Department of Eudcation and Science initiated a programme designed to support intensified research in the field of clinical pharmacology. Within the framework of the grant-supported research project 'Co-operative Clinical Pharmacology' at Westfaelische Wilhelms-Universitaet, the Department of Internal Medicine, the Department of Paediatric Haematology/Oncology, and the Institute of Pharmacology and Toxicology joined forces to form a Research Cooperative on Clinical Pharmacology. From the research activities grew involvement in some areas of patient care and the establishment of Clinical Pharmacology as an integral part of advanced studies. Research efforts at the Department of Internal Medicine focused on an improvement of treatment options in essential hypertensions, while at the Department of Paediatric Haematology/Oncology the focus was on developing analytical methods for cytotoxic drug monitoring from minimal sample volumes and optimising cytotoxic drug treatment in children based on methods of clinical pharmacology. The Research Co-operative on Clinical Pharmacology as a whole was structurally linked into the areas of research, teaching and patient care. (orig.)SIGLEAvailable from TIB Hannover: F00B390+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial

BACKGROUND: Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension. METHODS: 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo. FINDINGS: Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001). INTERPRETATION: Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common

ESH-ESC guidelines for the management of hypertension.

The following is a brief statement of the 2003 European Society of Hypertension (ESH)-European Society of Cardiology (ESC) guidelines for the management of arterial hypertension.The continuous relationship between the level of blood pressure and cardiovascular risk makes the definition of hypertension arbitrary. Since risk factors cluster in hypertensive individuals, risk stratification should be made and decision about the management should not be based on blood pressure alone, but also according to the presence or absence of other risk factors, target organ damage, diabetes, and cardiovascular or renal damage, as well as on other aspects of the patient's personal, medical and social situation. Blood pressure values measured in the doctor's office or the clinic should commonly be used as reference. Ambulatory blood pressure monitoring may have clinical value, when considerable variability of office blood pressure is found over the same or different visits, high office blood pressure is measured in subjects otherwise at low global cardiovascular risk, there is marked discrepancy between blood pressure values measured in the office and at home, resistance to drug treatment is suspected, or research is involved. Secondary hypertension should always be investigated.The primary goal of treatment of patient with high blood pressure is to achieve the maximum reduction in long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible factors identified, including smoking, dislipidemia, or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics.Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present.In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect or in special groups of patients. The choice of drugs will be influenced by many factors, including previous experience of the patient with antihypertensive agents, cost of drugs, risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes, patient's preference

Demonstrationsprojekt fuer ein Informationssystem zur oekolgischen Planung Teilprojekt Informationssystem ueber die Nutzungseignung des Bodens/Untergrundes

TIB Hannover: FR 2156+MF / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman