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The Cochrane Database of Systematic... Feb 2023Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. A number of pharmacological interventions have... (Review)
Review
BACKGROUND
Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. A number of pharmacological interventions have been used in the management of this condition, including betahistine, diuretics, antiviral medications and corticosteroids. The underlying cause of Ménière's disease is unknown, as is the way in which these treatments may work. The efficacy of these different interventions at preventing vertigo attacks, and their associated symptoms, is currently unclear.
OBJECTIVES
To evaluate the benefits and harms of systemic pharmacological interventions versus placebo or no treatment in people with Ménière's disease.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 September 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable Ménière's disease comparing betahistine, diuretics, antihistamines, antivirals or systemic corticosteroids with either placebo or no treatment. We excluded studies with follow-up of less than three months, or with a cross-over design (unless data from the first phase of the study could be identified). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) change in hearing, 6) change in tinnitus and 7) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 10 studies with a total of 848 participants. The studies evaluated the following interventions: betahistine, diuretics, antivirals and corticosteroids. We did not identify any evidence on antihistamines. Betahistine Seven RCTs (548 participants) addressed this comparison. However, we were unable to conduct any meta-analyses for our primary outcomes as not all outcomes were considered by every study, and studies that did report the same outcome used different time points for follow-up, or assessed the outcome using different methods. Therefore, we were unable to draw meaningful conclusions from the numerical results. Some data were available for each of our primary outcomes, but the evidence was low- or very low-certainty throughout. One study reported on the outcome 'improvement in vertigo' at 6 to ≤ 12 months, and another study reported this outcome at > 12 months. Four studies reported on the change in vertigo, but again all used different methods of assessment (vertigo frequency, or a global score of vertigo severity) or different time points. A single study reported on serious adverse events. Diuretics Two RCTs addressed this comparison. One considered the use of isosorbide (220 participants), and the other used a combination of amiloride hydrochloride and hydrochlorothiazide (80 participants). Again, we were unable to conduct any meta-analyses for our primary outcomes, as only one study reported on the outcome 'improvement in vertigo' (at 6 to ≤ 12 months), one study reported on change in vertigo (at 3 to < 6 months) and neither study assessed serious adverse events. Therefore, we were unable to draw meaningful conclusions from the numerical results. The evidence was all very low-certainty. Other pharmacological interventions We also identified one study that assessed antivirals (24 participants), and one study that assessed corticosteroids (16 participants). The evidence for these interventions was all very low-certainty. Again, serious adverse events were not considered by either study.
AUTHORS' CONCLUSIONS
The evidence for systemic pharmacological interventions for Ménière's disease is very uncertain. There are few RCTs that compare these interventions to placebo or no treatment, and the evidence that is currently available from these studies is of low or very low certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analyses of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits.
Topics: Adult; Humans; Meniere Disease; Tinnitus; Betahistine; Adrenal Cortex Hormones; Vertigo; Diuretics; Histamine Antagonists
PubMed: 36827524
DOI: 10.1002/14651858.CD015171.pub2 -
Clinical Cardiology Aug 2023This study aimed to evaluate the efficacy of single-pill combination (SPC) antihypertensive drugs in patients with uncontrolled essential hypertension. Through Searching... (Meta-Analysis)
Meta-Analysis Review
This study aimed to evaluate the efficacy of single-pill combination (SPC) antihypertensive drugs in patients with uncontrolled essential hypertension. Through Searching Pubmed, EMBASE, the Cochrane Library, and Web of Science collected only randomized controlled trials on the efficacy of single-pill combination antihypertensive drugs in people with uncontrolled essential hypertension. The search period is from the establishment of the database to July 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias Assessment, and statistical analyses were performed using Review Manage 5.3 and Stata 15.1 software. This review ultimately included 32 references involving 16 273 patients with uncontrolled essential hypertension. The results of the network meta-analysis showed that a total of 11 single-pill combination antihypertensive drugs were included, namely: Amlodipine/valsartan, Telmisartan/amlodipine, Losartan/HCTZ, Candesartan/HCTZ, Amlodipine/benazepril, Telmisartan/HCTZ, Valsartan/HCTZ, Irbesartan/amlodipine, Amlodipine/losartan, Irbesartan/HCTZ, and Perindopril/amlodipine. According to SUCRA, Irbesartan/amlodipine may rank first in reducing systolic blood pressure (SUCRA: 92.2%); Amlodipine/losartan may rank first in reducing diastolic blood pressure (SUCRA: 95.1%); Telmisartan/amlodipine may rank first in blood pressure control rates (SUCRA: 83.5%); Amlodipine/losartan probably ranks first in diastolic response rate (SUCRA: 84.5%). Based on Ranking Plot of the Network, we can conclude that single-pill combination antihypertensive drugs are superior to monotherapy, and ARB/CCB combination has better advantages than other SPC in terms of systolic blood pressure, diastolic blood pressure, blood pressure control rate, and diastolic response rate. However, due to the small number of some drug studies, the lack of relevant studies has led to not being included in this study, which may impact the results, and readers should interpret the results with caution.
Topics: Humans; Antihypertensive Agents; Losartan; Hypertension; Telmisartan; Irbesartan; Angiotensin Receptor Antagonists; Network Meta-Analysis; Hydrochlorothiazide; Valine; Drug Therapy, Combination; Angiotensin-Converting Enzyme Inhibitors; Amlodipine; Valsartan; Tetrazoles; Blood Pressure; Essential Hypertension
PubMed: 37432701
DOI: 10.1002/clc.24082 -
European Journal of Medical Research Nov 2022Traumatic brain injury (TBI) causes mortality and long-term disability among young adults and imposes a notable cost on the healthcare system. In addition to the first... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Traumatic brain injury (TBI) causes mortality and long-term disability among young adults and imposes a notable cost on the healthcare system. In addition to the first physical hit, secondary injury, which is associated with increased intracranial pressure (ICP), is defined as biochemical, cellular, and physiological changes after the physical injury. Mannitol and Hypertonic saline (HTS) are the treatment bases for elevated ICP in TBI. This systematic review and meta-analysis evaluates the effectiveness of HTS in the management of patients with TBI.
METHODS
This study was conducted following the Joanna Briggs Institute (JBI) methods and PRISMA statement. A systematic search was performed through six databases in February 2022, to find studies that evaluated the effects of HTS, on increased ICP. Meta-analysis was performed using comprehensive meta-analysis (CMA).
RESULTS
Out of 1321 results, 8 studies were included in the systematic review, and 3 of them were included in the quantitative synthesis. The results of the meta-analysis reached a 35.9% (95% CI 15.0-56.9) reduction in ICP in TBI patients receiving HTS, with no significant risk of publication bias (t-value = 0.38, df = 2, p-value = 0.73). The most common source of bias in our included studies was the transparency of blinding methods for both patients and outcome assessors.
CONCLUSION
HTS can significantly reduce the ICP, which may prevent secondary injury. Also, based on the available evidence, HTS has relatively similar efficacy to Mannitol, which is considered the gold standard therapy for TBI, in boosting patients' neurological condition and reducing mortality rates.
Topics: Humans; Young Adult; Intracranial Pressure; Brain Injuries; Saline Solution, Hypertonic; Intracranial Hypertension; Brain Injuries, Traumatic; Mannitol
PubMed: 36404350
DOI: 10.1186/s40001-022-00897-4 -
BMC Nephrology Jul 2020Due to the high incidence and mortality of sepsis-associated acute kidney injury, a significant number of studies have explored the causes of sepsis-associated acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Due to the high incidence and mortality of sepsis-associated acute kidney injury, a significant number of studies have explored the causes of sepsis-associated acute kidney injury (AKI). However, the opinions on relevant predictive risk factors remain inconclusive. This study aimed to provide a systematic review and meta-analysis to determine the predisposing factors for sepsis-associated AKI.
METHOD
A systematic literature search was performed in the Medline, Embase, Cochrane Library, PubMed, and Web of Science, databases, with an end-date of 25th May 2019. Valid data were retrieved in compliance with specific inclusion and exclusion criteria.
RESULT
Forty-seven observational studies were included for analysis, achieving a cumulative patient number of 55,911. The highest incidence of AKI was caused by septic shock. Thirty-one potential risk factors were included in the meta-analysis. Analysis showed that 20 factors were statistically significant. The odds ratio (OR) and 95% confidence interval (CI), as well as the prevalence of the most frequently-seen predisposing factors for sepsis-associated AKI, were as follows: septic shock [2.88 (2.36-3.52), 60.47%], hypertension [1.43 (1.20-1.70), 38.39%], diabetes mellitus [1.59 (1.47-1.71), 27.57%], abdominal infection [1.44 (1.32-1.58), 30.87%], the administration of vasopressors [2.95 (1.67-5.22), 64.61%], the administration of vasoactive drugs [3.85 (1.89-7.87), 63.22%], mechanical ventilation [1.64 (1.24-2.16), 68.00%], positive results from blood culture [1.60 (1.35-1.89), 41.19%], and a history of smoking [1.60 (1.09-2.36), 43.09%]. Other risk factors included cardiovascular diseases, coronary artery diseases, liver diseases, unknown infections, the administration of diuretics and ACEI/ARB, the infection caused by gram-negative bacteria, and organ transplantation.
CONCLUSION
Risk factors of S-AKI arise from a wide range of sources, making it difficult to predict and prevent this condition. Comorbidities, and certain drugs, are the main risk factors for S-AKI. Our review can provide guidance on the application of interventions to reduce the risks associated with sepsis-associated acute kidney injury and can also be used to tailor patient-specific treatment plans and management strategies in clinical practice.
Topics: Acute Kidney Injury; Bacteremia; Blood Culture; Diabetes Mellitus; Humans; Hypertension; Intraabdominal Infections; Respiration, Artificial; Risk Factors; Sepsis; Shock, Septic; Smoking; Vasoconstrictor Agents
PubMed: 32736541
DOI: 10.1186/s12882-020-01974-8 -
The Cochrane Database of Systematic... Jan 2022This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the... (Review)
Review
BACKGROUND
This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated.
OBJECTIVES
To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events.
SEARCH METHODS
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions.
SELECTION CRITERIA
Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information.
MAIN RESULTS
This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence).
AUTHORS' CONCLUSIONS
For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Humans; Hypertension; Pharmaceutical Preparations
PubMed: 35000192
DOI: 10.1002/14651858.CD003654.pub6 -
The American Journal of Cardiology Jul 2023Mineralocorticoid receptor antagonists (MRAs) are known to improve clinical outcomes in heart failure, particularly heart failure with reduced ejection fraction.... (Meta-Analysis)
Meta-Analysis Review
Mineralocorticoid receptor antagonists (MRAs) are known to improve clinical outcomes in heart failure, particularly heart failure with reduced ejection fraction. However, the effect of MRAs on the incidence of and recurrence of atrial fibrillation (AF) is not well established. Therefore, databases, such as PubMed, EMBASE, and Cochrane Central, were searched from inception to September 2021 for randomized controlled trials of MRAs with AF as an outcome. Risk ratios (RRs) with 95% confidence interval (CIs) were combined using the random-effects model. A total of 10 randomized controlled trials (n = 11,356) were included. Our pooled analysis demonstrates that MRAs reduce the risk of AF occurrence by 23% compared with the control therapy (RR 0.77, 95% CI 0.65 to 0.91, p = 0.003, I = 40%). Subgroup analysis demonstrated that MRAs reduced the risk of both new-onset AF (RR 0.84, 95% CI 0.61 to 1.16, p = 0.28, I = 43%) and recurrent AF (RR 0.73, 95% CI 0.59 to 0.90, p = 0.004, I = 26%) similarly; p interaction = 0.48. Our meta-analysis concludes that MRAs reduce the risk of development of AF overall, with consistent effects in new-onset and recurrent AF.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Atrial Fibrillation; Heart Failure; Incidence; Odds Ratio
PubMed: 37269781
DOI: 10.1016/j.amjcard.2023.04.038 -
Tremor and Other Hyperkinetic Movements... 2023Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1... (Review)
Review
BACKGROUND
Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in and . EA3-8 are reported in rare families. Advances in genetic testing have broadened the and phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists.
METHODS
A systematic literature review was performed in October 2022 for 'episodic ataxia' and 'paroxysmal ataxia', restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized.
RESULTS
EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (), epilepsy syndromes (), GLUT-1, mitochondrial disorders (), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause.
DISCUSSION
EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and treatment pathways. For atypical phenotypes, next generation genetic testing can aid diagnosis and guide treatment. Updated classification systems for EA are discussed which may assist diagnosis and management.
Topics: Humans; Ataxia; Cerebellar Ataxia; Acetazolamide; Mutation
PubMed: 37008993
DOI: 10.5334/tohm.747 -
Heart Failure Reviews Jan 2021Diuretics have an essential role in the management of heart failure (HF). However, each drug has its own benefit and side effect. Side effects include fluid, electrolyte... (Meta-Analysis)
Meta-Analysis Review
Diuretics have an essential role in the management of heart failure (HF). However, each drug has its own benefit and side effect. Side effects include fluid, electrolyte abnormalities, and acid-base disturbance. These adverse effects of diuretics predispose patients to serious cardiac arrhythmias and may increase the risk of arrhythmic mortality. Herein, we aim to summarize the relative efficacy and safety of all available diuretics used in the treatment of patients with HF. In June 2017, a systematic electronic database search was conducted in nine databases. All randomized controlled trials (RCTs) comparing the different diuretics used in HF were included for meta-analysis. The protocol was registered in Prospero with CRD42018084819. Among the included 54 studies (10,740 patients), 34 RCTs were eligible for quantitative network meta-analysis (NMA) and traditional meta-analysis while the other 20 studies were qualitatively analyzed. Our results showed that azosemide and torasemide caused a significant reduction in brain natriuretic peptide (BNP) level. Torasemide also caused a significant decrease in collagen volume fraction (CVF) and edema. No significant difference between the agents concerning glomerular filtration rate (GFR), water extraction, and sodium excretion was demonstrated. Regarding side effects, no significant difference among diuretics was observed in terms of hospital readmission and mortality rates. Diuretics are the main treatment of hypervolemia in HF patients. The choice of appropriate diuretic is essential for successful management and is mainly guided by patient clinical situations and the presence of other co-morbidities.
Topics: Diuretics; Furosemide; Heart Failure; Humans; Randomized Controlled Trials as Topic; Torsemide
PubMed: 32783109
DOI: 10.1007/s10741-020-10003-7 -
Chest Dec 2020Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however, given overlapping pathophysiologic properties of OSA and CSA, we hypothesized that acetazolamide is equally effective for both types. Prior reviews focused on specific subtypes of sleep apnea, study designs, and languages, thus including few studies (typically ≤3) limiting insights.
RESEARCH QUESTION
How efficacious is acetazolamide for sleep apnea, and is its effect modified by sleep apnea type or acetazolamide dose?
STUDY DESIGN AND METHODS
We queried MEDLINE, EMBASE, and ClinicalTrials.gov from inception until March 11, 2019. Any study in which adults with OSA/CSA received oral acetazolamide vs no acetazolamide (control) that reported sleep apnea-related outcomes was eligible, independent of study design or language. Two reviewers independently assessed eligibility and abstracted data. Primary outcomes were apnea-hypopnea index (AHI) and oxygen saturation nadir. Quality of evidence (QoE) was rated with the use of Grades of Recommendation Assessment, Development and Evaluation methods.
RESULTS
We included 28 studies (13 OSA/15 CSA; N = 542; N = 553) that enabled meta-analyses for 24 outcomes. Acetazolamide doses ranged from 36 to 1000 mg/d and treatment duration from 1 to 90 d (median, 6 d). Overall, acetazolamide vs control lowered the AHI by -0.7 effect sizes (95% CI, -0.83 to -0.58; I = 0%; moderate QoE) that corresponded to a reduction of 37.7% (95% CI, -44.7 to -31.3) or 13.8/h (95% CI, -16.3 to -11.4; AHI = 36.5/h). The AHI reduction was similar in OSA vs CSA, but significantly greater with higher doses (at least up to 500 mg/d). Furthermore, acetazolamide improved oxygen saturation nadir by +4.4% (95% CI, 2.3 to 6.5; I = 63%; no evidence of effect modification; very low QoE) and several secondary outcomes that included sleep quality measures and BP (mostly low QoE).
INTERPRETATION
Short-term acetazolamide improved both OSA and CSA. Rigorous studies with long-term follow up are warranted to assess Acetazolamide's value for the chronic treatment of patients with sleep apnea.
CLINICAL TRIAL REGISTRATION
PROSPERO (CRD42019147504).
Topics: Acetazolamide; Carbonic Anhydrase Inhibitors; Humans; Sleep Apnea, Central; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 32768459
DOI: 10.1016/j.chest.2020.06.078 -
The Cochrane Database of Systematic... Jul 2023Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity... (Review)
Review
BACKGROUND
Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity outcomes, and lowering blood pressure. First-line low-dose thiazide diuretics have been previously shown to have the best mortality and morbidity evidence when compared with placebo or no treatment. Head-to-head comparisons of thiazides with other blood pressure-lowering drug classes would demonstrate whether there are important differences.
OBJECTIVES
To compare the effects of first-line diuretic drugs with other individual first-line classes of antihypertensive drugs on mortality, morbidity, and withdrawals due to adverse effects in patients with hypertension. Secondary objectives included assessments of the need for added drugs, drug switching, and blood pressure-lowering.
SEARCH METHODS
Cochrane Hypertension's Information Specialist searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, and trials registers to March 2021. We also checked references and contacted study authors to identify additional studies. A top-up search of the Specialized Register was carried out in June 2022.
SELECTION CRITERIA
Randomized active comparator trials of at least one year's duration were included. Trials had a clearly defined intervention arm of a first-line diuretic (thiazide, thiazide-like, or loop diuretic) compared to another first-line drug class: beta-blockers, calcium channel blockers, alpha adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, direct renin inhibitors, or other antihypertensive drug classes. Studies had to include clearly defined mortality and morbidity outcomes (serious adverse events, total cardiovascular events, stroke, coronary heart disease (CHD), congestive heart failure, and withdrawals due to adverse effects).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We included 20 trials with 26 comparator arms randomizing over 90,000 participants. The findings are relevant to first-line use of drug classes in older male and female hypertensive patients (aged 50 to 75) with multiple co-morbidities, including type 2 diabetes. First-line thiazide and thiazide-like diuretics were compared with beta-blockers (six trials), calcium channel blockers (eight trials), ACE inhibitors (five trials), and alpha-adrenergic blockers (three trials); other comparators included angiotensin II receptor blockers, aliskiren (a direct renin inhibitor), and clonidine (a centrally acting drug). Only three studies reported data for total serious adverse events: two studies compared diuretics with calcium channel blockers and one with a direct renin inhibitor. Compared to first-line beta-blockers, first-line thiazides probably result in little to no difference in total mortality (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.84 to 1.10; 5 trials, 18,241 participants; moderate-certainty), probably reduce total cardiovascular events (5.4% versus 4.8%; RR 0.88, 95% CI 0.78 to 1.00; 4 trials, 18,135 participants; absolute risk reduction (ARR) 0.6%, moderate-certainty), may result in little to no difference in stroke (RR 0.85, 95% CI 0.66 to 1.09; 4 trials, 18,135 participants; low-certainty), CHD (RR 0.91, 95% CI 0.78 to 1.07; 4 trials, 18,135 participants; low-certainty), or heart failure (RR 0.69, 95% CI 0.40 to 1.19; 1 trial, 6569 participants; low-certainty), and probably reduce withdrawals due to adverse effects (10.1% versus 7.9%; RR 0.78, 95% CI 0.71 to 0.85; 5 trials, 18,501 participants; ARR 2.2%; moderate-certainty). Compared to first-line calcium channel blockers, first-line thiazides probably result in little to no difference in total mortality (RR 1.02, 95% CI 0.96 to 1.08; 7 trials, 35,417 participants; moderate-certainty), may result in little to no difference in serious adverse events (RR 1.09, 95% CI 0.97 to 1.24; 2 trials, 7204 participants; low-certainty), probably reduce total cardiovascular events (14.3% versus 13.3%; RR 0.93, 95% CI 0.89 to 0.98; 6 trials, 35,217 participants; ARR 1.0%; moderate-certainty), probably result in little to no difference in stroke (RR 1.06, 95% CI 0.95 to 1.18; 6 trials, 35,217 participants; moderate-certainty) or CHD (RR 1.00, 95% CI 0.93 to 1.08; 6 trials, 35,217 participants; moderate-certainty), probably reduce heart failure (4.4% versus 3.2%; RR 0.74, 95% CI 0.66 to 0.82; 6 trials, 35,217 participants; ARR 1.2%; moderate-certainty), and may reduce withdrawals due to adverse effects (7.6% versus 6.2%; RR 0.81, 95% CI 0.75 to 0.88; 7 trials, 33,908 participants; ARR 1.4%; low-certainty). Compared to first-line ACE inhibitors, first-line thiazides probably result in little to no difference in total mortality (RR 1.00, 95% CI 0.95 to 1.07; 3 trials, 30,961 participants; moderate-certainty), may result in little to no difference in total cardiovascular events (RR 0.97, 95% CI 0.92 to 1.02; 3 trials, 30,900 participants; low-certainty), probably reduce stroke slightly (4.7% versus 4.1%; RR 0.89, 95% CI 0.80 to 0.99; 3 trials, 30,900 participants; ARR 0.6%; moderate-certainty), probably result in little to no difference in CHD (RR 1.03, 95% CI 0.96 to 1.12; 3 trials, 30,900 participants; moderate-certainty) or heart failure (RR 0.94, 95% CI 0.84 to 1.04; 2 trials, 30,392 participants; moderate-certainty), and probably reduce withdrawals due to adverse effects (3.9% versus 2.9%; RR 0.73, 95% CI 0.64 to 0.84; 3 trials, 25,254 participants; ARR 1.0%; moderate-certainty). Compared to first-line alpha-blockers, first-line thiazides probably result in little to no difference in total mortality (RR 0.98, 95% CI 0.88 to 1.09; 1 trial, 24,316 participants; moderate-certainty), probably reduce total cardiovascular events (12.1% versus 9.0%; RR 0.74, 95% CI 0.69 to 0.80; 2 trials, 24,396 participants; ARR 3.1%; moderate-certainty) and stroke (2.7% versus 2.3%; RR 0.86, 95% CI 0.73 to 1.01; 2 trials, 24,396 participants; ARR 0.4%; moderate-certainty), may result in little to no difference in CHD (RR 0.98, 95% CI 0.86 to 1.11; 2 trials, 24,396 participants; low-certainty), probably reduce heart failure (5.4% versus 2.8%; RR 0.51, 95% CI 0.45 to 0.58; 1 trial, 24,316 participants; ARR 2.6%; moderate-certainty), and may reduce withdrawals due to adverse effects (1.3% versus 0.9%; RR 0.70, 95% CI 0.54 to 0.89; 3 trials, 24,772 participants; ARR 0.4%; low-certainty). For the other drug classes, data were insufficient. No antihypertensive drug class demonstrated any clinically important advantages over first-line thiazides.
AUTHORS' CONCLUSIONS
When used as first-line agents for the treatment of hypertension, thiazides and thiazide-like drugs likely do not change total mortality and likely decrease some morbidity outcomes such as cardiovascular events and withdrawals due to adverse effects, when compared to beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers.
Topics: Aged; Female; Humans; Male; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Disease; Diabetes Mellitus, Type 2; Diuretics; Heart Failure; Hypertension; Stroke; Thiazides; Middle Aged
PubMed: 37439548
DOI: 10.1002/14651858.CD008161.pub3