ABSTRACT: This study aimed to investigate the association between cardiovascular drugs and depression/anxiety in patients with cardiovascular disease (CVD). This meta-analysis was registered in PROSPERO (International Prospective Register of Systematic Reviews; CRD42020197839) and conducted in accordance with the MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. The PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases were systematically searched to identify all available studies on this topic. Random-effects multivariate meta-regression was performed to investigate the sources of study heterogeneity. Review Manager version 5.3 and Stata 12.0 were used for data analyses. This meta-analysis included 54 studies with a total number of 212,640 patients. Overall, in patients with CVD, aspirin (odds ratio [OR]:0.91, 95% confidence interval [CI]:0.86-0.96, P = 0.02) was associated with a lower risk of depression, while calcium channel blockers (CCB) (OR:1.21, 95%CI:1.05-1.38, P = 0.008), diuretics (OR:1.34, 95%CI:1.14-1.58, P = 0.0005), and nitrate esters (OR:1.32, 95%CI:1.08-1.61, P = 0.006) were associated with a higher risk of depression, additionally, statin (OR:0.79, 95%CI:0.71-0.88, P < 0.0001) was associated with a lower risk of anxiety, but diuretics (OR:1.39, 95%CI:1.26-1.52, P < 0.00001) was associated with a higher risk of anxiety. Subgroup analysis presented that, in patients with hypertension, β-blockers were associated with a higher risk of depression (OR:1.45, 95%CI:1.26-1.67, P < 0.00001); in patients with coronary artery disease (CAD), statin (OR:0.77, 95%CI:0.59-0.99, P = 0.04), and aspirin (OR:0.85, 95%CI:0.75-0.97, P = 0.02) were associated with a lower risk of depression, while CCB (OR:1.32, 95%CI:1.15-1.51, P < 0.0001) and diuretics (OR:1.36, 95%CI:1.12-1.64, P = 0.002) were associated with a higher risk of depression, additionally, diuretics was associated with a higher risk of anxiety (OR:1.41, 95%CI:1.28-1.55, P < 0.00001); in patients with heart failure, nitrate esters (OR:1.93, 95%CI:1.19-3.13, P = 0.007), and diuretics (OR:1.58, 95%CI: 1.02-2.43, P = 0.04) were associated with a higher risk of depression. The use of cardiovascular drugs should be considered when evaluating depression or anxiety in patients with CVD to improve the care and treatment of these patients.
BACKGROUND: Approximately half of people with heart failure have chronic kidney disease (CKD). Pharmacological interventions for heart failure in people with CKD have the potential to reduce death (any cause) or hospitalisations for decompensated heart failure. However, these interventions are of uncertain benefit and may increase the risk of harm, such as hypotension and electrolyte abnormalities, in those with CKD.
OBJECTIVES: This review aims to look at the benefits and harms of pharmacological interventions for HF (i.e., antihypertensive agents, inotropes, and agents that may improve the heart performance indirectly) in people with HF and CKD.
SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies through 12 September 2019 in consultation with an Information Specialist and using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA: We included randomised controlled trials of any pharmacological intervention for acute or chronic heart failure, among people of any age with chronic kidney disease of at least three months duration.
DATA COLLECTION AND ANALYSIS: Two authors independently screened the records to identify eligible studies and extracted data on the following dichotomous outcomes: death, hospitalisations, worsening heart failure, worsening kidney function, hyperkalaemia, and hypotension. We used random effects meta-analysis to estimate treatment effects, which we expressed as a risk ratio (RR) with 95% confidence intervals (CI). We assessed the risk of bias using the Cochrane tool. We applied the GRADE methodology to rate the certainty of evidence.
MAIN RESULTS: One hundred and twelve studies met our selection criteria: 15 were studies of adults with CKD; 16 studies were conducted in the general population but provided subgroup data for people with CKD; and 81 studies included individuals with CKD, however, data for this subgroup were not provided. The risk of bias in all 112 studies was frequently high or unclear. Of the 31 studies (23,762 participants) with data on CKD patients, follow-up ranged from three months to five years, and study size ranged from 16 to 2916 participants. In total, 26 studies (19,612 participants) reported disaggregated and extractable data on at least one outcome of interest for our review and were included in our meta-analyses. In acute heart failure, the effects of adenosine A1-receptor antagonists, dopamine, nesiritide, or serelaxin on death, hospitalisations, worsening heart failure or kidney function, hyperkalaemia, hypotension or quality of life were uncertain due to sparse data or were not reported. In chronic heart failure, the effects of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) (4 studies, 5003 participants: RR 0.85, 95% CI 0.70 to 1.02; I2 = 78%; low certainty evidence), aldosterone antagonists (2 studies, 34 participants: RR 0.61 95% CI 0.06 to 6.59; very low certainty evidence), and vasopressin receptor antagonists (RR 1.26, 95% CI 0.55 to 2.89; 2 studies, 1840 participants; low certainty evidence) on death (any cause) were uncertain. Treatment with beta-blockers may reduce the risk of death (any cause) (4 studies, 3136 participants: RR 0.69, 95% CI 0.60 to 0.79; I2 = 0%; moderate certainty evidence). Treatment with ACEi or ARB (2 studies, 1368 participants: RR 0.90, 95% CI 0.43 to 1.90; I2 = 97%; very low certainty evidence) had uncertain effects on hospitalisation for heart failure, as treatment estimates were consistent with either benefit or harm. Treatment with beta-blockers may decrease hospitalisation for heart failure (3 studies, 2287 participants: RR 0.67, 95% CI 0.43 to 1.05; I2 = 87%; low certainty evidence). Aldosterone antagonists may increase the risk of hyperkalaemia compared to placebo or no treatment (3 studies, 826 participants: RR 2.91, 95% CI 2.03 to 4.17; I2 = 0%; low certainty evidence). Renin inhibitors had uncertain risks of hyperkalaemia (2 studies, 142 participants: RR 0.86, 95% CI 0.49 to 1.49; I2 = 0%; very low certainty). We were unable to estimate whether treatment with sinus node inhibitors affects the risk of hyperkalaemia, as there were few studies and meta-analysis was not possible. Hyperkalaemia was not reported for the CKD subgroup in studies investigating other therapies. The effects of ACEi or ARB, or aldosterone antagonists on worsening heart failure or kidney function, hypotension, or quality of life were uncertain due to sparse data or were not reported. Effects of anti-arrhythmic agents, digoxin, phosphodiesterase inhibitors, renin inhibitors, sinus node inhibitors, vasodilators, and vasopressin receptor antagonists were very uncertain due to the paucity of studies.
AUTHORS' CONCLUSIONS: The effects of pharmacological interventions for heart failure in people with CKD are uncertain and there is insufficient evidence to inform clinical practice. Study data for treatment outcomes in patients with heart failure and CKD are sparse despite the potential impact of kidney impairment on the benefits and harms of treatment. Future research aimed at analysing existing data in general population HF studies to explore the effect in subgroups of patients with CKD, considering stage of disease, may yield valuable insights for the management of people with HF and CKD.
BACKGROUND AND OBJECTIVES: Statins showed mixed results in heart failure (HF) patients. The benefits in major HF outcomes, including all-cause mortality and sudden cardiac death (SCD), have always been discordant across systematic reviews and meta-analyses. We intended to systematically identify and appraise the available evidence that evaluated the effectiveness of statins in clinical outcomes for HF patients.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: We searched, until April 28, 2016: Medline, Embase, ISI Web of Science and EBM reviews (Cochrane DSR, ACP journal club, DARE, CCTR, CMR, HTA, and NHSEED), checked clinicaltrials.gov for ongoing trials and manually searched references of included studies.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We identified 24 randomized clinical trials that evaluated the efficacy of statins for HF patients. All randomized clinical trials were assessed for risk of bias and pooled together in a meta-analysis. Pre-specified outcomes were sudden cardiac death, all-cause mortality, and hospitalization for worsening heart failure.
RESULTS: Statins did not reduce sudden cardiac death (SCD) events in HF patients [relative risk (RR) 0.92, 95% confidence interval (CI) 0.70 to 1.21], all-cause mortality [RR 0.88, 95% CI 0.75 to 1.02] but significantly reduced hospitalization for worsening heart failure (HWHF) although modestly [RR 0.79, 95% CI 0.66 to 0.94]. Nevertheless, estimated predictive intervals were insignificant in SCD, all-cause mortality and HWHF [RR, 0.54 to 1.63, 0.64 to 1.19, and 0.54 to 1.15], respectively. An important finding was the possible presence of publication bias, small-study effects and heterogeneity of the trials conducted in HF patients.
CONCLUSIONS: Statins do not reduce sudden cardiac death, all-cause mortality, but may slightly decrease hospitalization for worsening heart failure in HF patients. The evaluation of the risk of biases suggested moderate quality of the published results. Until new evidence is available, this study supports the 2013 ACCF/AHA guidelines to not systematically prescribe statins in "only" HF patients, which should help avoid unnecessary polypharmacy.
BACKGROUND: Acute heart failure (AHF) is one of the most common diagnoses assigned to emergency department (ED) patients who are hospitalized. Despite its high prevalence in the emergency setting, the diagnosis of AHF in ED patients with undifferentiated dyspnea can be challenging.
OBJECTIVES: The primary objective of this study was to perform a systematic review and meta-analysis of the operating characteristics of diagnostic elements available to the emergency physician for diagnosing AHF. Secondary objectives were to develop a test-treatment threshold model and to calculate interval likelihood ratios (LRs) for natriuretic peptides (NPs) by pooling patient-level results.
METHODS: PubMed, EMBASE, and selected bibliographies were searched from January 1965 to March 2015 using MeSH terms to address the ability of the following index tests to predict AHF as a cause of dyspnea in adult patients in the ED: history and physical examination, electrocardiogram, chest radiograph (CXR), B-type natriuretic peptide (BNP), N-terminal proB-type natriuretic peptide (NT-proBNP), lung ultrasound (US), bedside echocardiography, and bioimpedance. A diagnosis of AHF based on clinical data combined with objective test results served as the criterion standard diagnosis. Data were analyzed using Meta-DiSc software. Authors of all NP studies were contacted to obtain patient-level data. The Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) for systematic reviews was utilized to evaluate the quality and applicability of the studies included.
RESULTS: Based on the included studies, the prevalence of AHF ranged from 29% to 79%. Index tests with pooled positive LRs ≥ 4 were the auscultation of S3 on physical examination (4.0, 95% confidence interval [CI] = 2.7 to 5.9), pulmonary edema on both CXR (4.8, 95% CI = 3.6 to 6.4) and lung US (7.4, 95% CI = 4.2 to 12.8), and reduced ejection fraction observed on bedside echocardiogram (4.1, 95% CI = 2.4 to 7.2). Tests with low negative LRs were BNP < 100 pg/mL (0.11, 95% CI = 0.07 to 0.16), NT-proBNP < 300 pg/mL (0.09, 95% CI = 0.03 to 0.34), and B-line pattern on lung US LR (0.16, 95% CI = 0.05 to 0.51). Interval LRs of BNP concentrations at the low end of "positive" results as defined by a cutoff of 100 pg/mL were substantially lower (100 to 200 pg/mL; 0.29, 95% CI = 0.23 to 0.38) than those associated with higher BNP concentrations (1000 to 1500 pg/mL; 7.12, 95% CI = 4.53 to 11.18). The interval LR of NT-proBNP concentrations even at very high values (30,000 to 200,000 pg/mL) was 3.30 (95% CI = 2.05 to 5.31).
CONCLUSIONS: Bedside lung US and echocardiography appear to the most useful tests for affirming the presence of AHF while NPs are valuable in excluding the diagnosis.
OBJECTIVES: This study aims to compare lipophilic and hydrophilic statin therapy on clinical outcomes of heart failure (HF) using a systematic review and an adjusted indirect comparison meta-analysis. Outcomes were all-cause mortality, cardiovascular mortality, cardiovascular hospitalization and hospitalization for worsening HF.
METHODS: We conducted a search of PubMed, EMBASE and Cochrane databases until 31st December 2014 for randomized control trials (RCTs) in HF evaluating statins versus placebo. Identified RCTs and their respective abstracted information were grouped according to statin type evaluated and analyzed separately. Outcomes were initially pooled with the Peto's one-step method, producing odd ratios (OR) and 95 % confidence intervals (CI) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons of lipophilic versus hydrophilic statin for each outcome.
RESULTS: Thirteen studies involving 10,966 patients were identified and analyzed. Lipophilic statins were superior to hydrophilic rosuvastatin regarding all-cause mortality (OR 0 · 50; 95 % CI, 0 · 11-0 · 89; p = 0 · 01), cardiovascular mortality (OR 0 · 61; 0 · 25-0 · 97; p = 0 · 009), and hospitalization for worsening HF (OR 0 · 52; 0 · 21-0 · 83; p = 0 · 0005). However, both statins were comparable with regards to cardiovascular hospitalization [OR 0 · 80 (0 · 31, 1 · 28); p = 0 · 36].
CONCLUSIONS: Lipophilic statin treatment shows significant decreases in all-cause mortality, cardiovascular mortality and hospitalization for worsening HF compared with rosuvastatin treatment. This meta-analysis provides preliminary evidence that lipophilic statins offer better clinical outcomes in HF till data from head to head comparisons are available.
BACKGROUND: Refractory congestive heart failure (RCHF) is associated with a high mortality rate and is a major contributor to hospital admissions. Peritoneal dialysis (PD) is an option to control volume overload and perhaps improve outcomes in this challenging patient population. The aim of this systematic review is to describe the relative risk-benefit ratio based on data reported regarding the use of PD in RCHF. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. An electronic search of PubMed, Embase, and the Cochrane Library was performed to identify relevant studies published from January 1951 to February 2014. Eligible studies selected were prospective or retrospective adult population studies on PD in the setting of RCHF. The following clinical outcomes were used to assess PD therapy: (1) hospitalization rates; (2) heart function; (3) renal function; (4) fluid overload, and (5) adverse clinical outcomes.
SUMMARY: Of 864 citations, we excluded 843 citations and included 21 studies (n = 673 patients). After PD, hospitalization days declined significantly (p = 0.0001), and heart function improved significantly (left ventricular ejection fraction: p = 0.0013; New York Heart Association classification: p = 0.0000). There were no statistically significant differences in glomerular filtration rate after PD treatment in non-chronic kidney disease stage 5D patients (p = 0.1065). Among patients treated with PD, body weight decreased significantly (p = 0.0006). The yearly average peritonitis rate was 14.5%, and the average yearly mortality was 20.3%.
KEY MESSAGES: This systematic review suggests that PD may be an effective and safe therapeutic tool for patients with RCHF.
OBJECTIVES: To determine and compare the diagnostic accuracy of serum natriuretic peptide levels (B type natriuretic peptide, N terminal probrain natriuretic peptide (NTproBNP), and mid-regional proatrial natriuretic peptide (MRproANP)) in people presenting with acute heart failure to acute care settings using thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure.
DESIGN: Systematic review and diagnostic meta-analysis.
DATA SOURCES: Medline, Embase, Cochrane central register of controlled trials, Cochrane database of systematic reviews, database of abstracts of reviews of effects, NHS economic evaluation database, and Health Technology Assessment up to 28 January 2014, using combinations of subject headings and terms relating to heart failure and natriuretic peptides.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible studies evaluated one or more natriuretic peptides (B type natriuretic peptide, NTproBNP, or MRproANP) in the diagnosis of acute heart failure against an acceptable reference standard in consecutive or randomly selected adults in an acute care setting. Studies were excluded if they did not present sufficient data to extract or calculate true positives, false positives, false negatives, and true negatives, or report age independent natriuretic peptide thresholds. Studies not available in English were also excluded.
RESULTS: 37 unique study cohorts described in 42 study reports were included, with a total of 48 test evaluations reporting 15 263 test results. At the lower recommended thresholds of 100 ng/L for B type natriuretic peptide and 300 ng/L for NTproBNP, the natriuretic peptides have sensitivities of 0.95 (95% confidence interval 0.93 to 0.96) and 0.99 (0.97 to 1.00) and negative predictive values of 0.94 (0.90 to 0.96) and 0.98 (0.89 to 1.0), respectively, for a diagnosis of acute heart failure. At the lower recommended threshold of 120 pmol/L, MRproANP has a sensitivity ranging from 0.95 (range 0.90-0.98) to 0.97 (0.95-0.98) and a negative predictive value ranging from 0.90 (0.80-0.96) to 0.97 (0.96-0.98). At higher thresholds the sensitivity declined progressively and specificity remained variable across the range of values. There was no statistically significant difference in diagnostic accuracy between plasma B type natriuretic peptide and NTproBNP.
CONCLUSIONS: At the rule-out thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure, plasma B type natriuretic peptide, NTproBNP, and MRproANP have excellent ability to exclude acute heart failure. Specificity is variable, and so imaging to confirm a diagnosis of heart failure is required. There is no statistical difference between the diagnostic accuracy of plasma B type natriuretic peptide and NTproBNP. Introduction of natriuretic peptide measurement in the investigation of patients with suspected acute heart failure has the potential to allow rapid and accurate exclusion of the diagnosis.
This study aimed to investigate the association between cardiovascular drugs and depression/anxiety in patients with cardiovascular disease (CVD). This meta-analysis was registered in PROSPERO (International Prospective Register of Systematic Reviews; CRD42020197839) and conducted in accordance with the MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. The PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases were systematically searched to identify all available studies on this topic. Random-effects multivariate meta-regression was performed to investigate the sources of study heterogeneity. Review Manager version 5.3 and Stata 12.0 were used for data analyses. This meta-analysis included 54 studies with a total number of 212,640 patients. Overall, in patients with CVD, aspirin (odds ratio [OR]:0.91, 95% confidence interval [CI]:0.86-0.96, P = 0.02) was associated with a lower risk of depression, while calcium channel blockers (CCB) (OR:1.21, 95%CI:1.05-1.38, P = 0.008), diuretics (OR:1.34, 95%CI:1.14-1.58, P = 0.0005), and nitrate esters (OR:1.32, 95%CI:1.08-1.61, P = 0.006) were associated with a higher risk of depression, additionally, statin (OR:0.79, 95%CI:0.71-0.88, P < 0.0001) was associated with a lower risk of anxiety, but diuretics (OR:1.39, 95%CI:1.26-1.52, P < 0.00001) was associated with a higher risk of anxiety. Subgroup analysis presented that, in patients with hypertension, β-blockers were associated with a higher risk of depression (OR:1.45, 95%CI:1.26-1.67, P < 0.00001); in patients with coronary artery disease (CAD), statin (OR:0.77, 95%CI:0.59-0.99, P = 0.04), and aspirin (OR:0.85, 95%CI:0.75-0.97, P = 0.02) were associated with a lower risk of depression, while CCB (OR:1.32, 95%CI:1.15-1.51, P < 0.0001) and diuretics (OR:1.36, 95%CI:1.12-1.64, P = 0.002) were associated with a higher risk of depression, additionally, diuretics was associated with a higher risk of anxiety (OR:1.41, 95%CI:1.28-1.55, P < 0.00001); in patients with heart failure, nitrate esters (OR:1.93, 95%CI:1.19-3.13, P = 0.007), and diuretics (OR:1.58, 95%CI: 1.02-2.43, P = 0.04) were associated with a higher risk of depression. The use of cardiovascular drugs should be considered when evaluating depression or anxiety in patients with CVD to improve the care and treatment of these patients.
