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Metformin Use in Patients with Historical Contraindications or Precautions [Internet]

Metformin is a biguanide oral hypoglycemic used primarily for treating type 2 diabetes mellitus (T2D). Evidence suggests that, in addition to improving glycemic control, metformin is associated with improved all-cause and cardiovascular mortality and decreased risk of some cancers. However, clinicians have been advised by the U.S. Food and Drug Administration (FDA) to exercise caution in prescribing metformin to individuals with chronic kidney disease (CKD), unstable congestive heart failure (CHF), chronic liver disease (CLD), and older age due to perceived risk of side effects, including lactic acidosis (LA).

Evidence-based Synthesis Program - Department of Veterans Affairs (US).

Version: September 2016
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Screening for Dementia [Internet]

To produce an evidence-based review to support recommendations from the US Preventive Services Task Force (USPSTF) concerning dementia syndrome screening in primary care settings.

Systematic Evidence Reviews - Agency for Healthcare Research and Quality (US).

Version: June 2003
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Interventions for adult Eustachian tube dysfunction: a systematic review

This systematic review found insufficient evidence to draw conclusions about the effectiveness of any intervention for adults with Eustachian tube dysfunction (ETD). The quality of the evidence was generally poor. Evidence was insufficient to allow recommendation of a trial of any particular intervention. Further research is needed to establish a definition of ETD, its relation to broader middle ear ventilation problems and clear diagnostic criteria.

Health Technology Assessment - NIHR Journals Library.

Version: July 2014
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Clinical Practice Guidelines We Can Trust

Advances in medical, biomedical and health services research have reduced the level of uncertainty in clinical practice. Clinical practice guidelines (CPGs) complement this progress by establishing standards of care backed by strong scientific evidence. CPGs are statements that include recommendations intended to optimize patient care. These statements are informed by a systematic review of evidence and an assessment of the benefits and costs of alternative care options. Clinical Practice Guidelines We Can Trust examines the current state of clinical practice guidelines and how they can be improved to enhance healthcare quality and patient outcomes.

National Academies Press (US).

Version: 2011
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Chronic Heart Failure: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care: Partial Update [Internet]

This guideline is a partial update of NICE Guideline No 5: Chronic Heart Failure - national clinical guideline for diagnosis and management in primary and secondary care (2003). The aim of the 2003 guideline was to offer best practice advice on the care of adult patients (aged 18 years or older) who have symptoms or a diagnosis of chronic heart failure. It defined the most effective combination of symptoms, signs and investigations required to establish a diagnosis of heart failure, and those which would influence therapy or provide important prognostic information. It also gave guidance on the treatment, monitoring and support of patients with heart failure.

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: August 2010
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Efficacy of azilsartan medoxomil with chlorthalidone in hypertension

Azilsartan medoxomil (AZL) is the most recently approved angiotensin receptor blocker (ARB) for treating patients with hypertension. A fixed-dose combination product with AZL and the thiazide-like diuretic chlorthalidone (CLD) is now available to treat individuals who require additional blood pressure lowering. For this review, a literature search was conducted using MEDLINE and the keywords and MeSH terms azilsartan, azilsartan medoxomil, chlorthalidone, thiazide, blood pressure and hypertension. References for retrieved articles were also scanned for relevant citations. No language restrictions were used. AZL is structurally related to candesartan and has been shown to provide more potent angiotensin receptor antagonism versus other ARBs. CLD is a thiazide-like diuretic with a longer half-life and greater blood pressure lowering efficacy than hydrochlorothiazide. The combination of AZL plus CLD has superior efficacy to other ARBs alone or in combination with hydrochlorothiazide based on extensive evaluation in clinical trials. This superior efficacy is not offset by a large imbalance in clinically important adverse events.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Aliskiren vs. other antihypertensive drugs in the treatment of hypertension: a meta-analysis

To investigate the antihypertensive effects and tolerability of aliskiren in comparison with other antihypertensive drugs and placebo in patients with hypertension, a meta-analysis was performed of studies published between 1950 and 2012. A systematic literature search of MEDLINE and the Cochrane Library was conducted for randomized controlled trials. Weighted mean differences and relative risk with 95% confidence intervals were calculated for continuous and dichotomous data, respectively. In all, 14 studies with 6741 participants were included in the present meta-analysis. Nine studies included trial arms with placebo, four included angiotensin (Ang) AT1 receptor blockers (ARBs), three included Ang-converting enzyme inhibitors (ACEIs), two included calcium channel blockers (CCBs), one included a β-blocker, and one included hydrochlorothiazide (HCTZ). We found that aliskiren, which lowered blood pressure (BP) effectively in patients with mild-to-moderate hypertension, was similar to HCTZ but inferior to CCBs in BP reduction, response rates and control rates. Furthermore, aliskiren was superior to ACEIs in lowering diastolic BP (DBP), while it had similar effects to ACEIs on systolic BP (SBP) reduction, response rates and control rates. Additionally, the present meta-analysis showed the superiority of atenolol over aliskiren in DBP reduction and BP response but showed that atenolol was inferior in SBP reduction and BP control. No difference was found in the rates of therapeutic response between aliskiren and ARBs, while more patients achieved BP control with aliskiren. Further studies will be needed to determine the antihypertensive effects and tolerability of aliskiren in comparison with other antihypertensive drugs.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

The efficacy and safety of triple vs dual combination of angiotensin ii receptor blocker and calcium channel blocker and diuretic: a systematic review and meta-analysis

Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple combination of angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Medical literature between January 1990 and April 2012 was reviewed systematically and data from eligible studies were abstracted. Data were analyzed using random-effects models. Of the 224 studies screened, 7563 eligible patients from 11 studies were included. Triple combinations of ARBs (olmesartan or valsartan), CCBs (amlodipine), and diuretics (hydrochlorothiazide) at any dose provided more blood pressure reduction in office and 24-hour ambulatory measurements than any dual combination of these molecules (P<.0001 for both). Significantly more patients achieved blood pressure targets with triple combinations (odds ratio, 2.16; P<.0001). Triple combinations did not increase adverse event risk (odds ratio, 0.96; P=.426). Triple combinations at any dose seem to decrease blood pressure more effectively than dual combination of the same molecules without any remarkable risk elevation for adverse events. Further prospective studies evaluating the efficacy and safety of triple combinations, especially in the form of single pills, are required.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

A meta-analysis of randomized trials of telmisartan vs. valsartan therapy for blood pressure reduction

A previous meta-analysis of six randomized head-to-head trials suggests that the blood pressure (BP)-lowering capabilities of telmisartan may be comparable to those of valsartan. We performed an updated meta-analysis of telmisartan vs. valsartan therapy for the reduction of BP in hypertensive patients. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through August 2012 using web-based search engines (PubMed, OVID). Eligible studies were prospective randomized controlled trials examining telmisartan vs. valsartan therapy and reporting clinic BP as an outcome. For each study, the data regarding changes from baseline to final clinic systolic BP (SBP) and diastolic BP (DBP) in both the telmisartan and valsartan groups were used to generate mean differences (MDs) and 95% confidence intervals (CIs). Of the 62 potentially relevant articles initially screened, 17 reports about prospective randomized controlled clinical trials of telmisartan vs. valsartan therapy, including a total of 5422 patients with hypertension, were identified and included. Pooled analysis suggested significant differences in BP reductions among the patients randomized to telmisartan vs. valsartan therapy (MD for SBP, -2.04 mm Hg; 95% CI, -2.80 to -1.28 mm Hg; P<0.00001; MD for DBP, -1.08 mm Hg; 95% CI, -1.55 to -0.62 mm Hg; P<0.00001). When data from the monotherapy and combination therapy (with hydrochlorothiazide) trials were pooled separately, telmisartan therapy was associated with a statistically significant difference in BP reductions relative to valsartan therapy in both the monotherapy and combination therapy groups. In conclusion, telmisartan therapy appears to reduce BP more than valsartan therapy in patients with hypertension.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

AIMS: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Comparison of the efficacy of candesartan and losartan: a meta-analysis of trials in the treatment of hypertension

This review found that candesartan was associated with significantly greater reductions in blood pressure in patients with hypertension compared with losartan. The results of this review should be interpreted with some caution, and the reliability of the authors' conclusions is uncertain due to the absence of a formal quality assessment and possible biases in the review process.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

The development of new-onset type 2 diabetes associated with choosing a calcium channel blocker compared to a diuretic or beta-blocker

This review concluded that calcium-channel blockers for the treatment of hypertension appear to reduce the risk of developing new-onset type two diabetes mellitus compared with treatment with β-blockers and/or diuretics. However, given the differences between the studies and several potential limitations of the review methodology, the reliability of the authors' conclusions is unclear.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2007

Race and ethnicity in trials of antihypertensive therapy to prevent cardiovascular outcomes: a systematic review

The authors' conclusion appears to be that in cardiovascular disease prevention trials of antihypertensive therapies, treatment efficacy was similar for white and ethnic minorities for the primary outcomes. However, owing to the methodology used in the review, these results should be considered as exploratory rather than conclusive.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2007

Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis

This review concluded that fixed-dose combinations of antihypertensive agents were associated with a significant improvement in compliance and with non significant beneficial trends in blood pressure and adverse effects. These conclusions were supported by the data presented, but their reliability is unclear due to limitations in the quality assessment.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

Cardiovascular outcomes in high-risk patients without heart failure treated with ARBs: a systematic review and meta-analysis

This review found no evidence that angiotensin II type I receptor antagonists (ARBs) confered cardiovascular protection akin to angiotensin-converting enzyme inhibitors. ARBs may have had a small benefit related to stroke risk, but this was difficult to quantify. The authors' conclusions reflected the evidence presented, but due to some methodological biases the reliability of the results are unclear.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2009

Relation of beta-blocker-induced heart rate lowering and cardioprotection in hypertension

This review found that in people with hypertension a reduction in heart rate achieved through use of beta-blockers increased the risk of cardiovascular events and death. There were some methodological problems with the review. It was possible that confounding factors may have influenced the results and this was not investigated. The conclusions may be unreliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2008

The association of antihypertensive medication use with risk of cognitive decline and dementia: a meta-analysis of longitudinal studies

This review found that antihypertensive medication use could decrease the risk of the development of vascular dementia and any dementia, but not the risk of new onset Alzheimer's disease, cognitive impairment or decline. Methodological flaws and the potential for bias mean that the results should be interpreted with caution and the reliability of the authors' conclusions is unclear.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

A systematic review and meta-analysis of aliskiren and angiotension receptor blockers in the management of essential hypertension

This review concluded that aliskiren provided similar reductions in blood pressure to angiotensin receptor blockers (ARBs) in people with hypertension and no difference in adverse effects. Aliskiren combined with ARBs proved more effective in reducing blood pressure than either therapy alone. Data came from short-term studies that did not assess clinical outcomes, but the authors' conclusions appear reasonable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Fixed-dose combinations improve medication compliance: a meta-analysis

This review found that fixed-dose combination medications increase medication compliance, compared with free-drug regimens, in patients with chronic conditions. Although the data appear to support these conclusions, they should be interpreted with some degree of caution because of limitations in the search and a failure to assess study quality.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2007

Atenolol in hypertension: is it a wise choice?

This review assessed the effect of atenolol on cardiovascular morbidity and mortality in patients with hypertension. The authors concluded that atenolol may not be a suitable treatment option for patients with hypertension, and queried its use as a reference drug in trials. Limitations in the reporting of the review process and the lack of a validity assessment weaken this conclusion.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2004

Systematic Reviews in PubMed

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