Beta-blockers with alpha receptor activity also produce vasodilatation, Vary by drug from once to several times daily. Based on the physiologic characteristics of the older hypertensive (. Study drug withdrawal was significantly lower with ARB compared with ACEi. The GDG considered all of them to be underpowered to detect a significant blood pressure difference between diuretic treatments. This calculation includes age (over 50 in men and 60 in women), smoking (in the current or last three years), diabetes (treated or not), stroke (before age 45), and some form of dyslipidemia. Only two studies reported ethnicity and in these 86% of participants were Caucasian. The trial was designed similarly to trials of secondary cardiovascular prevention rather than treatment of hypertension; the trial population were not hypertensive and the study is not included in this review. Lifestyle interventions and pharmacological treatment form the cornerstone of therapy; lifestyle modification has been shown to reduce BP by as much as 10mmHg (NICE, 2011). In the absence of a published cost effectiveness analysis, current UK drugs costs were presented to the GDG to inform decision making. 2 months placebo run-in, 12 weeks TD drug, 2 months placebo washout, 12 weeks alternate TD drug. Low quality trials were defined as those which had no blinding or allocation concealment. [2006], If blood pressure is not controlled by Step 1 treatment, offer step 2 treatment with a CCB in combination with either an ACE inhibitor or an ARBj. The SYST-EUR trial enrolled patients with isolated systolic hypertension, one third of whom were male; ethnicity was not reported. Study withdrawal was also significantly lower in patients randomised to treatment with the combination of ACEi+CCB. These were not included because they did not answer this part of the question (TDs vs. TDs) and were not included in the first part of the question (TDs vs. placebo/other a-HT classes) because they did not meet inclusion criteria (ie. Studies were excluded if they had sample sizes of N<200, follow-up of <1 year or populations which were exclusively diabetic or had chronic kidney disease. Most people with primary hypertension are a low-to intermediate risk of heart failure and have an increased risk of developing diabetes, this suggests that CCBs would be the most cost-effective step 1 therapy for most people aged over 55 years. Apart from any fair dealing for the purposes of research or private study, criticism or review, as permitted under the Copyright, Designs and Patents Act, 1988, no part of this publication may be reproduced, stored or transmitted in any form or by any means, without the prior written permission of the publisher or, in the case of reprographic reproduction, in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK. CCBs and ARBs) due to generics becoming available. Hypertension is defined as a systolic blood pressure greater than 140 mmHg and a diastolic pressure of more than 90 mmHg. The recommendation for step 1 treatment for younger people was an “A” drug. … One study 511 found that 4th line therapy with spironolactone was better than doxazosin for reduction in SBP and DBP [low quality]. Patients receiving placebo withdrew from treatment at an average rate of 10.7% per year. Withdrawal per year from active therapy was similar (Incident Risk Difference per year 0.6%, 95%CI: −0.2% to 1.3%). This review of pharmacological treatment strategies was supported by an updated cost-effectiveness analysis comparing different treatments with updated costings. It was reassuring that the other studies in the analysis, albeit much smaller but studying a more typical hypertensive population, were consistent with the findings of ONTARGET. Informed consent should be obtained and documented. When the blood in the arteries puts increased force on the artery wall, many problems can arise including stroke, heart attack and heart failure. The dihydropyridine class (e.g., nifedipine) has more potent direct vasodilator effects and may be more likely to produce peripheral edema and reflex tachycardia. The GDG considered the effect of this uncertainty about important outcomes in reaching their conclusions. The patient has been recently started on a treatment regimen that includes sodium nitroprusside. If this trial is removed from the MA then heterogeneity is reduced to more acceptable levels of 0% and the effect becomes NS. The analysis also showed that beta-blockers were the least effective and may actually increase blood pressure variability. Another important conclusion is that for most people, CCBs were found to be the most cost-effective treatment option for initial treatment of primary hypertension. Three studies163,347 NOTE: ALL (except one) OF THESE TRIALS STATED THAT THE PREPARATION WAS SR. ALL JUST STATED INDAPMIDE AND THE DOSE. Summary of effect sizes for each comparison included in the meta-analysis. The relative risks for ARBs were also updated based on new ACEi vs ARB data. The trials on which the cost-effectiveness calculations are based did not, in general, show large differences in clinical outcomes between drug classes. Beta-blockers are not a preferred initial therapy for hypertension. The model considered patients with essential hypertension seen in primary care, excluding those with pre-existing cardiovascular disease (CVD), heart failure (HF) or diabetes. 95% confidence interval crosses both 1) no effect and 2) appreciable benefit or harm and non-appreciable benefit or harm. It was designed to be run separately for different cohorts, defined by age (55, 65, 75 and 85) and sex. Another important consideration is that spironolactone is a potassium sparing diuretic and may cause hyperkalaemia, especially when combined with an ACE-inhibitor or ARB, as will be the case for most people with resistant hypertension treated according to the algorithm recommended by this guideline. The patient has completed a health history form. For simplicity only first-line drugs were considered. Addition of ACEi at 6 weeks if target BP not met. No relevant cost effectiveness analyses comparing ACEi versus ARBs were identified. The GDG concluded that it follows from the evidence reviews cited above that the recommended step 3 treatment should be; A (ACEi or ARB) + CCB + D (thiazide-like diuretic, i.e. There was no data on other clinical outcomes. Meet a former Red Sox pitcher who picked security over an uncertain future, Atrial Septal Defect and patent foramen ovale. Consequently, this arm of the ALLHAT study was closed. Inhibition of angiotensin coverting enzyme and reduced angiotensin II production. Vasodilation and moderate diuresis (increased excretion of sodium, potassium and water). There is consistent evidence, from a systematic review of 5,479 patients who stopped taking anti-hypertensive medication and who were followed up for at least a year434, and from a subsequent study of 503 patients who were also followed up for a year435, that patients are more likely to remain normotensive if they are younger, have lower blood pressure and have been treated with only one drug. SYST-EUR featured stepped care, with additional drugs added if necessary. ), when safe to use and when tolerated, can be an effective means of further lowering blood pressure. Evidence profile comparing ACEi versus other antihypertensive classes (TD, CCB or alpha) in black people and non-black people (data from Piller et al., 2006). The TONE study enrolled patients who had been taking only one antihypertensive drug or a combination of a diuretic and a non-diuretic for a mean duration of 11.7 years. The major limitations to the use of ACE inhibitors in older hypertensive patients are the development of hyperkalemia (especially in those with renal insufficiency) and the potential for development of renal failure in the setting of bilateral renal artery stenosis. [2004], Offer people aged 80 years and over the same antihypertensive drug treatment as people aged 55–80 years, taking into account any comorbidities. The analysis examined data for the four most commonly used thiazide-type diuretics; i) classical thiazide diuretics (e.g. If the target blood pressure goal is not obtained at a maximal dose of the initial agent following several months of treatment, therapy may either be switched to an alternate class or a second drug from another class may be added. To address concerns that calcium antagonist therapy may be deleterious in those with diabetes, a subgroup analysis of the Syst-Eur population found similar beneficial effects in the diabetic population as had been noted in nondiabetics. chlortalidone or inadapamide) are considered a suitable alternative for those who cannot tolerate a CCB or who have developed, or are at high risk of developing heart failure. The GDG discussed the potential use of other drug classes for resistant hypertension and noted that treatments such as higher doses of thiazide type diuretics, alpha blockers and beta blockers have been used as add-on therapy in clinical trials at step 2 and 3 but not necessarily at step 4. However, the studies included in the previous guidelines did not give data for the ACEi vs. CCB arms in black people and did not give the incidences of angioedema, which these newer subgroup analyses have looked at. 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