Blood pressure lowering efficacy of angiotensin receptor blockers for primary hypertension.
ABSTRACT Angiotensin receptor blockers (ARBs) are widely prescribed for hypertension so it is essential to determine and compare their effects on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAE).
To quantify the dose-related systolic and/or diastolic BP lowering efficacy of ARBs versus placebo in the treatment of primary hypertension.
We searched CENTRAL (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to February 2007), EMBASE (1988 to February 2007) and reference lists of articles.
Double-blind, randomized, controlled trials evaluating the BP lowering efficacy of fixed-dose monotherapy with an ARB compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension.
Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. WDAE information was collected from the trials.
Forty six RCTs evaluated the dose-related trough BP lowering efficacy of 9 ARBs in 13 451 participants with a baseline BP of 156/101 mm Hg. The data do not suggest that any one ARB is better or worse at lowering BP. A dose of 1/8 or 1/4 of the manufacturers' maximum recommended daily dose (Max) achieved a BP lowering effect that was 60 to 70% of the BP lowering effect of Max. A dose of 1/2 Max achieved a BP lowering effect that was 80% of Max. ARB doses above Max did not significantly lower BP more than Max. Due to evidence of publication bias, the largest trials provide the best estimate of the trough BP lowering efficacy for ARBs as a class of drugs: -8 mm Hg for SBP and -5 mm Hg for DBP. ARBs reduced BP measured 1 to 12 hours after the dose by about 12/7 mm Hg.
The evidence from this review suggests that there are no clinically meaningful BP lowering differences between available ARBs. The BP lowering effect of ARBs is modest and similar to ACE inhibitors as a class; the magnitude of average trough BP lowering for ARBs at maximum recommended doses and above is -8/-5 mmHg. Furthermore, 60 to 70% of this trough BP lowering effect occurs with recommended starting doses. The review did not provide a good estimate of the incidence of harms associated with ARBs because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
Article: Differential clinical profile of candesartan compared to other angiotensin receptor blockers.[show abstract] [hide abstract]
ABSTRACT: The advantages of blood pressure (BP) control on the risks of heart failure and stroke are well established. The renin-angiotensin system plays an important role in volume homeostasis and BP regulation and is a target for several groups of antihypertensive drugs. Angiotensin II receptor blockers represent a major class of antihypertensive compounds. Candesartan cilexetil is an angiotensin II type 1 (AT) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Oral candesartan 8-32 mg once daily is recommended for the treatment of adult patients with hypertension. Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy, and migraine in different populations of adult patients including patients with coexisting type 2 diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in BP treatment, is a highly selective compound with high potency, a long duration of action, and a tolerability profile similar to placebo. The most important and recent data from clinical trials regarding candesartan cilexetil will be reviewed in this article.Vascular Health and Risk Management 01/2011; 7:749-59.
Article: Does outcome reporting bias "cause" cancer? Risks associated with hidden data on Angiotensin receptor blockers.[show abstract] [hide abstract]
ABSTRACT: Conflicting reports have been published regarding the influence of angiotensin receptor blockers (ARBs) on the incidence of cancer. One meta-analysis reported a 1% absolute increase in the incidence of cancer associated with ARBs over 4 years. Contrasting findings were reported in an industry-sponsored meta-analysis and in another meta-analysis, both of which showed no difference in the incidence of cancer in ARB treatment groups relative to control groups. The US Food and Drug Administration has recently asserted that evidence does not support an association between ARBs and the development of cancer. The current review compares the 3 published meta-analyses assessing the association between ARBs and cancer and shows that outcome reporting bias contributed to the conflicting results. Given the prevalence of this form of bias in the scientific literature, the processes for systematic reviews and meta-analyses are under siege, and there is an important role for health care regulators to play. If all outcome data from clinical trials were to be reported in the public domain, independent analyses could be performed and the results of industry-sponsored trials verified. Furthermore, if regulators were to mandate the publication, in the public domain, of all clinical outcomes collected in clinical trials, outcome reporting bias could be eliminated.The Canadian journal of hospital pharmacy 09/2012; 65(5):387-93.
Article: Antihypertensive efficacy of hydrochlorothiazide as evaluated by ambulatory blood pressure monitoring: a meta-analysis of randomized trials.[show abstract] [hide abstract]
ABSTRACT: The purpose of this study was to evaluate the antihypertensive efficacy of hydrochlorothiazide (HCTZ) by ambulatory blood pressure (BP) monitoring. HCTZ is the most commonly prescribed antihypertensive drug worldwide. More than 97% of all HCTZ prescriptions are for 12.5 to 25 mg per day. The antihypertensive efficacy of HCTZ by ambulatory BP monitoring is less well defined. A systematic review was made using Medline, Cochrane, and Embase for all the randomized trials that assessed 24-h BP with HCTZ in comparison with other antihypertensive drugs. Fourteen studies of HCTZ dose 12.5 to 25 mg with 1,234 patients and 5 studies of HCTZ dose 50 mg with 229 patients fulfilled the inclusion criteria. The decrease in 24-h BP with HCTZ dose 12.5 to 25 mg was systolic 6.5 mm Hg (95% confidence interval: 5.3 to 7.7 mm Hg) and diastolic 4.5 mm Hg (95% confidence interval: 3.1 to 6.0 mm Hg) and was inferior compared with the 24-h BP reduction of angiotensin-converting enzyme inhibitors (mean BP reduction 12.9/7.7 mm Hg; p < 0.003), angiotensin-receptor blockers (mean BP reduction 13.3/7.8 mm Hg; p < 0.001), beta-blockers (mean BP reduction 11.2/8.5 mm Hg; p < 0.00001), and calcium antagonists (mean BP reduction 11.0/8.1 mm Hg; p < 0.05). There was no significant difference in both systolic (p = 0.30) and diastolic (p = 0.15) 24-h BP reduction between HCTZ 12.5 mg (5.7/3.3 mm Hg) and HCTZ 25 mg (7.6/5.4 mm Hg). However, with HCTZ 50 mg, the reduction in 24-h BP was significantly higher (12.0/5.4 mm Hg) and was comparable to that of other agents. The antihypertensive efficacy of HCTZ in its daily dose of 12.5 to 25 mg as measured in head-to-head studies by ambulatory BP measurement is consistently inferior to that of all other drug classes. Because outcome data at this dose are lacking, HCTZ is an inappropriate first-line drug for the treatment of hypertension.Journal of the American College of Cardiology 02/2011; 57(5):590-600. · 14.16 Impact Factor