A 26-week, prospective, open-label, uncontrolled, multicenter study to evaluate the effect of an escalating-dose regimen of trandolapril on change in blood pressure in treatment-naive and concurrently treated adult hypertensive subjects (TRAIL).
This study evaluated the effectiveness of an escalating-dose regimen of trandolapril in subjects with stage 1 or stage 2 hypertension.
This was a 26-week, prospective, open-label,multicenter study in Canadian primary care centers. Subjects with hypertension who were treatment naive or whose disease was uncontrolled on current first-line antihypertensive monotherapy were treated with trandolapril for 26 weeks alone or in addition to their current treatment. Uncontrolled hypertension was defined as systolic/diastolic blood pressure (SBP/DBP) >or=140/90 mm Hg in subjects with no other risk factors or >or=130/80 mm Hg in subjects with diabetes or kidney disease. Trandolapril therapy was initiated at 1 mg/d and was titrated as required to 2 or 4 mg at 4 and 9 weeks after initiation of treatment, respectively, in those not achieving BP targets. At 14 weeks after treatment initiation, subjects not achieving BP targets could receive a combination of trandolapril 4 mg plus a calcium channel blocker (verapamil 240 mg) with or without a diuretic. Primary outcome was the percentage of patients reaching target BP after 14 weeks.
A total of 1683 subjects from 192 general practice clinics across Canada completed the 14-week trandolapril dose-optimization phase, and 1650 completed the full 26-week follow-up. Mean (SD) age was 56.6 (12.6) years, and 49.2% of the subjects were men. At baseline, 82.4% (1359/1650) of subjects were antihypertensive-treatment naive. At the trial end, 73.4% (95% CI, 70.9-75.9) of subjects achieved a target level of SBP/DBP
To provide updated, evidence-based recommendations for the therapy of hypertension in adults.
For patients with hypertension, a number of antihypertensive agents may control blood pressure. Randomized trials evaluating first-line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed.
The health outcomes that were considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence.
MEDLINE was searched for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension. Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other published studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts.
A high value was placed on the avoidance of cardiovascular morbidity and mortality.
Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood-pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality.
The present document contains detailed recommendations pertaining to treatment thresholds, target blood pressures, and choice of agents in various settings in patients with hypertension. The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus, the amalgamation of the previous sections on treatment of hypertension in the young and old into one section, increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke. Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk, the presence and/or absence of target organ damage, and comorbidities.
All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving high levels of consensus are reported here. These guidelines will continue to be updated annually.
To provide updated, evidence-based recommendations for the management of hypertension in adults.
For patients who require pharmacological therapy for hypertension, a number of antihypertensive agents may be used. Randomized trials evaluating first-line therapy with diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), alpha-blockers, centrally acting agents or angiotensin receptor antagonists were reviewed. Also, randomized trials evaluating other agents, such as statins or acetylsalicylic acid, in patients with hypertension were reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. In addition, other relevant outcomes such as development of end-stage renal disease or changes in blood pressure were examined where appropriate.
MEDLINE searches were conducted from November 2001 to October 2003 to update the 2001 Recommendations for the management of hypertension. Reference lists were scanned, experts were contacted, and the personal files of the subgroup members and authors were used to identify additional published studies. All relevant articles were reviewed and appraised independently, using prespecified levels of evidence by content and methodology experts.
This document contains detailed recommendations and supporting evidence on treatment thresholds, target blood pressures and choice of agents for hypertensive patients with or without comorbidities. Lifestyle modifications are a key component of any antiatherosclerotic management strategy and detailed recommendations are contained in a separate document. Key recommendations for pharmacotherapy include the following: treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and comorbidities, with particular attention to systolic blood pressure; blood pressure should be lowered to 140/90 mmHg or less in all patients, and 130/80 mmHg or less in those with diabetes mellitus or renal disease (125/75 mmHg or less in those with nondiabetic renal disease and more than 1 g of proteinuria per day); most adults with hypertension require more than one agent to achieve target blood pressures; for adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), ACE inhibitors (in non-Blacks), long-acting dihydropyridine CCBs or angiotensin receptor antagonists; other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine CCBs or angiotensin receptor antagonists; certain comorbidities provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or thiazides in patients with diabetes mellitus without albuminuria) are appropriate first-line therapies; and in patients with mild to moderate nondiabetic renal disease, ACE inhibitors are recommended; all hypertensive patients should have their fasting lipids screened and those with dyslipidemia should be treated using the thresholds, targets and agents as per the Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease; and selected patients with hypertension should also receive statin and/or acetylsalicylic acid therapy.
All recommendations were graded according to the strength of the evidence and voted on by the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. Individuals with irreconcilable competing interests (declared by all members, compiled and circulated before the meeting) relative to any specific recommendation were excluded from voting on that recommendation. Only recommendations achieving at least 70% consensus are reported here. These guidelines will continue to be updated annually.
The present article is a summary of the theme, the key recommendations for management of hypertension and the supporting clinical evidence of the 2010 Canadian Hypertension Education Program (CHEP). In 2010, CHEP emphasizes the need for health care professionals to stay informed about hypertension through automated updates at www.htnupdate.ca. A new interactive Internet-based lecture series will be available in 2010 and a program to train community hypertension leaders will be expanded. Patients can also sign up to receive regular updates in a pilot program at www.myBPsite.ca. In 2010, the new recommendations include consideration for using automated office blood pressure monitors, new targets for dietary sodium for the prevention and treatment of hypertension that are aligned with the national adequate intake values, and recommendations for considering treatment of selected hypertensive patients at high risk with calcium channel blocker/angiotensin-converting enzyme inhibitor combinations and the use of angiotensin receptor blockers.
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Cites: Lancet. 2007 Dec 15;370(9604):2044-5318063027
Acute administration of a single dose of valsartan improves left ventricular functions: a pilot study to assess the role of tissue velocity echocardiography in patients with systemic arterial hypertension in the TVE-valsartan study I.
BACKGROUND: The advent of colour-coded tissue velocity echocardiography (TVE) has now made it possible to quantify left ventricular (LV) functions in patients with systemic arterial hypertension (HTN). Hypothesis In this project, we have studied the cardiac effects of a single dose of orally administered valsartan in patients with known HTN. METHODS: Fifty-five patients with HTN with a mean age of 56 +/- 10 years were given an early morning dose of 80 mg valsartan withholding regular antihypertensive medications on the day of investigation. TVE images, acquired on VIVID systems were digitized for postprocessing of longitudinal and radial peak systolic velocities, strain rate, and systolic and diastolic time intervals before (pre) and 5 h after (post) administration of the drug. RESULTS: Blood pressure (mmHg) pre and post, respectively, were 147 +/- 15 versus 137 +/- 14 systolic and 90 +/- 7 versus 86 +/- 7 diastolic (all P
To assess the utilization of antihypertensive drugs among uncomplicated hypertensive patients in Finland between 2000 and 2006 and to calculate the achievable reduction in cardiovascular morbidity, with intensified antihypertensive treatment.
From the databases of the Social Insurance Institution of Finland, 428,986 treated hypertensives without diabetes or cardiac disease (further named uncomplicated hypertensives) in 2000 and 591,206 in 2006, respectively, were identified. In addition, from the Health 2000 survey representing the whole Finnish adult population, 729 uncomplicated hypertensives were determined to assess their characteristics and control of hypertension. Applying Law's meta-analyses we calculated the reduction of blood pressure (BP) by intensifying the treatment with low-dose antihypertensive regimens for those with a BP =140/90?mmHg.
The nationwide data suggests a relative overuse of beta-blockers. Combination antihypertensive treatment increased relatively 8%, while at least three drug combinations increased from 19.8% to 21.6% between 2000 and 2006. However, calculated prevalence of controlled BP (
Regulation of sympathoadrenal activity has been a long-time target in the management of hypertension. Regulation of ß-adrenoceptor (ßAR) function has been the most therapeutically important of these targets. The development of effective antihypertensive treatments based on ßAR antagonism paralleled the elucidation of the molecular basis of ß-adrenergic effects by the family of ßARs, which are members of the G-protein-coupled receptor (GPCR) superfamily. ßARs serve as the extracellular face of the transmembrane signalling pathway that results in the consequent activation of heterotrimeric G-proteins and the activation of several other newly appreciated signalling molecules that include ß-arrestins and GPCR kinases (GRKs). The aggregate effect of the activation of these signalling pathways mediates the response to ßAR activation. Paradoxically, the hypertensive state is characterized by impaired ßAR responsiveness. This defect is common to many other receptor systems linked to the stimulator G protein (Gs) and adenylyl cyclase activation. This impairment is principally mediated by receptor-G-protein uncoupling, which has been linked to increased expression and activity of GRK2.
There are two independent head injury outcome studies using the "Lund concept", and both showed a mortality rate of about 10%, and a favourable outcome (Glasgow outcome scale, GOS 4 and 5) of about 70%. The Lund concept aims at controlling intracranial pressure, and improving microcirculation around contusions. Intracranial pressure is controlled by maintaining a normal colloid osmotic pressure and reducing the hydrostatic capillary pressure. Microcirculation is improved by ensuring strict normovolaemia and reducing sympathetic discharge. The endogenous substance prostacyclin with its antiaggregatory/antiadhesive effects may further improve microcirculation, which finds support from a microdialysis-based clinical study and an experimental brain trauma study. The present clinical outcome study aims at evaluating whether the previously obtained good outcome with the Lund therapy can be reproduced, and whether the addition of prostacyclin has any adverse side-effects.
All 31 consecutive patients with severe head injury, Glasgow coma scale (GCS) 10 months after the injury.
One patient died, another suffered vegetative state and 7 severe disability. Of the 22 patients with favourable outcome, 19 showed good recovery and 3 moderate disability. No adverse side-effects of prostacyclin were observed.
The outcome results from previous studies using the Lund therapy were reproduced, and no adverse side-effects of low-dose prostacyclin were observed.
BACKGROUND: In an elderly, community based population we aimed at investigating antihypertensive and lipid lowering medication use in relation to own and familiar cardiovascular morbidity and diabetes mellitus, as well as to lifestyle factors and general health. We also examined levels of blood pressure in untreated and treated residents, to investigate factors correlating with blood pressure control. METHODS: A health survey carried out in 1997-9 in the county of Hordaland, Norway included a self-administered questionnaire mailed to 4,338 persons born in 1925-7. Drug use the day prior to filling in the questionnaire was reported. A health check-up was carried out, where their systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI), and serum-cholesterol level were recorded. RESULTS: One third of respondents used one or more antihypertensive drugs, while 13% of men and women were treated with a statin. Diabetes mellitus, own or relatives'cardiovascular disease, having quit smoking, physical inactivity, and overweight correlated with antihypertensive treatment. Mean blood pressure was lower in respondents not on treatment. Among those on treatment, 38% of men and 29% of women had reached a target BP-level of lower than 140/90 mm Hg. Own cardiovascular disease and a low BMI correlated with good BP-control. CONCLUSION: One third of 70-74 year old individuals living in the community used one or more antihypertensive drugs. Only around one third of those treated had reached a target BP-level of less than 140/90 mm Hg. Own cardiovascular disease and a low BMI correlated with good BP-control.
Antihypertensive (anti-HT) drugs targeting renin-angiotensin-aldosterone (RAA)- system have been associated with improved prostate cancer (PCa)-specific survival. Challenge is that often multiple drugs are used simultaneously. We evaluated the association between use of anti-HT drugs and PCa survival among 14,422 surgically treated Finnish PCa patients. Information on drug purchases was obtained from a national prescription database. We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of PCa death and initiation of androgen deprivation therapy (ADT) with adjustment for age, tumor extent, use of statins and for Charlson Comorbidity Index. Angiotensin-converting enzyme (ACE)- inhibitors, angiotensin- receptor (ATR)-blockers, diuretics, calcium-channel blockers, beta-blockers and other anti-HT drugs were analyzed as separate time-dependent variables to model simultaneous use. Overall anti-HT drugs were associated with an increased risk of PCa death. Conversely use of ATR-blockers was associated with decreased risk of PCa death (HR: 0.43, 95% CI: 0.26-0.72 and HR: 0.60, 95% CI 0.37-0.97 for pre- and post-diagnostic use). Similar risk decrease was not observed in other drug groups. Anti-HT drugs were also associated with an increased risk of starting ADT, with the exception of ATR-blockers (HR: 0.81 CI:0.71-0.92). ATR- blockers differ from other anti-HT drugs as the survival is better in users of this drug group. The result partly supports the role of RAA system in PCa progression. Nevertheless, the risk decrease was not observed in ACE-inhibitor users. Further research is needed to elucidate the molecular mechanism for the potential anticancer effect of ATR- blockers.