Cláudio David

Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients : meta-analysis of randomised controlled trials

Abstract Objective To evaluate the clinical benefit of lipid lowering drug treatment in patients with and without diabetes mellitus, for primary and secondary prevention. Design Systematic review and meta-analysis. Data sources Cochrane, Medline, Embase, and reference lists up to April 2004. Study selection Randomised, placebo controlled, double blind trials with a follow-up of at least three years that evaluated lipid lowering drug treatment in patients with and without diabetes mellitus. Data extraction Two independent reviewers extracted data. The primary outcome was major coronary events defined as coronary heart disease death, non-fatal myocardial infarction, or myocardial revascularisation procedures. Results Twelve studies were included. Lipid lowering drug treatment was found to be at least as effective in diabetic patients as in non-diabetic patients. In primary prevention, the risk reduction for major coronary events was 21% (95% confidence interval 11% to 30%; P < 0.0001) in diabetic patients and 23% (12% to 33%; P = 0.0003) in non-diabetic patients. In secondary prevention, the corresponding risk reductions were 21% (10% to 31%; P = 0.0005) and 23% (19% to 26%; P ≤ 0.00001). However, the absolute risk difference was three times higher in secondary prevention. When results were adjusted for baseline risk, diabetic patients benefited more in both primary and secondary prevention. Blood lipids were reduced to a similar degree in both groups. Conclusions The evidence that lipid lowering drug treatment (especially statins) significantly reduce cardiovascular risk in diabetic and non-diabetic patients is strong and suggests that diabetic patients benefit more, in both primary and secondary prevention. Future research should define the threshold for treatment of these patients and the desired target lipid concentrations, especially for primary prevention.

Skin antiseptics in venous puncture-site disinfection for prevention of blood culture contamination: systematic review with meta-analysis.

Blood cultures drawn by venous puncture are common clinical procedures for the detection of bacteraemia. Blood culture contamination (BCC) can lead to clinical misinterpretation and unnecessary expenses. We aimed to systematically review randomised controlled trials (RCTs) with skin antiseptics for prevention of contamination in venous-puncture drawn blood cultures. We conducted database search using CENTRAL (Cochrane Library issue April 2010), MEDLINE, EMBASE and mRCT, in June 2010. All RCTs testing skin antiseptics in venous-puncture drawn blood cultures were retrieved. Relative risk (RR) of the BCC outcome was analysed by random effects method using confidence interval (CI) of 95%. Studies were assessed by one review author and checked by another. Six studies were identified. Single-trial comparisons showed that alcoholic iodine tincture was better than non-alcoholic povidone-iodine, and isopropyl/acetone/povidone-iodine showed superiority against isopropyl/povidone-iodine. Meta-analysis demonstrated that alcoholic chlorhexidine was better than non-alcoholic povidone-iodine (RR: 0.33; 95% CI: 0.24-0.46) in 4757 blood cultures from two trials. Alcoholic solutions were better than non-alcoholic products (0.53; 0.31-0.90) in 21,300 blood cultures from four studies. Two trials with 13,418 blood cultures showed that iodine tincture was not superior to povidone-iodine in BCC prevention (0.79; 0.54-1.18). Alcoholic iodine was not different from non-alcoholic iodine (0.79; 0.53-1.17). Comparison of chlorhexidine vs iodine compounds was not conclusive. Alcohol alone was not inferior to iodinated products for prevention of contamination in venous-puncture drawn blood cultures. The association of alcohol and povidone-iodine did not seem to be useful. Alcoholic chlorhexidine solutions reduced blood culture false positives compared with aqueous povidone-iodine.

Educational Strategies to Reduce Serum Phosphorus in Hyperphosphatemic Patients With Chronic Kidney Disease: Systematic Review With Meta-analysis

OBJECTIVE To systematically review educational strategies for phosphorus reduction in patients with hyperphosphatemia and chronic kidney disease (CKD). DESIGN Systematic review with meta-analysis. DATA SOURCES CENTRAL, MEDLINE, EMBASE, and mRCT databases were assessed in June 2010. STUDY SELECTION Randomized controlled trials evaluating educational strategies related to diet in hyperphosphatemic patients with CKD. DATA EXTRACTION AND SYNTHESIS METHOD: Study characteristics, phosphorus levels, and calcium-phosphorus product levels were retrieved. Jadad scale was used for quality assessment. Mean difference (MD) and 95% confidence intervals (CIs) were calculated by random effects method. RESULTS Seven randomized controlled trials were retrieved with a total of 524 patients with hyperphosphatemia and CKD. Educational strategies reduced phosphorus levels with an MD of -0.72 mg/dL (95% CI: -1.11 to -0.33, P < .01). Sensitivity analysis of trials with follow-up of <4 months did not show any benefit of the intervention, but educational intervention for ≥ 4 months showed an MD of -1.07 (95% CI: -1.49 to -0.64, P < .01). Calcium-phosphorus product level was improved in 227 evaluated patients from 5 trials with an MD of -5.22 mg(2)/dL(2) (95% CI: -9.48 to -0.98, P = .02, and I(2) = 58%). Sensitivity analysis removed the source of heterogeneity and resulted in an MD of -3.02 (95% CI: -6.51 to 0.47, P = .09). CONCLUSIONS Education helped reduce phosphorus levels in hyperphosphatemic patients with CKD, particularly those on dialysis.

Rate versus rhythm control in atrial fibrillation and clinical outcomes: Updated systematic review and meta-analysis of randomized controlled trials

Atrial fibrillation is the most frequently occurring sustained cardiac arrhythmia and is associated with a significantly increased risk of thromboembolic events and death. We sought to compare the clinical efficacy of rate and rhythm control strategies in patients with non-postoperative atrial fibrillation. We searched the PubMed database and the Cochrane Central Register of Controlled Trials for randomized controlled trials comparing rate versus rhythm control in patients with atrial fibrillation. Studies were retrieved and we analysed major clinical outcomes. Risk ratios (RRs) and 95% confidence intervals were calculated assuming random effects due to the clinical heterogeneity of the study populations. Eight randomized controlled trials were identified, with a total of 7499 patients with atrial fibrillation. There were no significant differences in the effects of rate and rhythm control on any outcome: all-cause mortality (RR: 0.95; CI: 0.86-1.05), cardiovascular mortality (RR: 0.99; CI: 0.87-1.13), arrhythmic/sudden death (RR: 1.12; CI: 0.91-1.38), ischaemic stroke (RR: 0.89; CI: 0.52-1.53), systemic embolism (RR: 0.89; CI: 0.69-1.14) and major bleeding (RR: 1.10; CI: 0.89-1.36). Updated data pooled from a large population of patients with atrial fibrillation suggests that rate and rhythm control strategies have similar effects on major clinical outcomes. Other factors, including individual preferences, comorbidities, drug tolerance and cost issues, should be considered when choosing the approach for these patients.

Tolerability of Angiotensin-Receptor Blockers in Patients with Intolerance to Angiotensin-Converting Enzyme Inhibitors

BackgroundBetween 5% and 20% of patients treated with angiotensin-converting enzyme inhibitors (ACE inhibitors) develop intolerance. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) can be used as an alternative treatment.ObjectiveIn this study we aimed to evaluate the tolerability of ARBs in patients with intolerance to ACE inhibitors.Data SourcesThe electronic databases PubMed, MEDLINE/EMBASE via Dialog, CENTRAL, and ISI Web of Knowledge were searched.Study SelectionRandomized controlled trials (RCTs) evaluating ARBs in patients with intolerance to ACE inhibitors were selected.Data SynthesisRisk ratio (RR) and 95% confidence intervals (CIs) were estimated assuming the random effects method. We found 11 RCTs comparing ARBs with ACE inhibitors, diuretics, or placebo, and one RCT comparing high-dose versus low-dose ARB.ResultsARBs had fewer cough events versus ACE inhibitors (RR 0.37; 95% CI 0.28, 0.48). ARBs had drug discontinuation (RR 0.99; 95% CI 0.84, 1.17) and cough risk (RR 1.01; 95% CI 0.74, 1.39) rates similar to placebo. Angioedema risk with ARBs was also similar to placebo (RR 1.62; 95% CI 0.17, 15.79). Compared with placebo, hypotension (RR 2.63; 95% CI 1.77, 3.92), renal dysfunction (RR 2.07; 95% CI 1.45, 2.95) and hyperkalemia (RR 3.37; 95% CI 1.60, 7.11) were more frequent with ARBs.ConclusionsACE inhibitor rechallenge should be discouraged in patients with previous intolerance to ACE inhibitors due to a higher risk of cough. ARBs had cough and angioedema incidences similar to placebo. Despite a significantly higher incidence of hypotension, renal dysfunction and hyperkalemia, discontinuation of ARBs was similar to placebo.

Tolerability of angiotensin-receptor blockers in patients with intolerance to angiotensin-converting enzyme inhibitors: a systematic review and meta-analysis.

BACKGROUND Between 5% and 20% of patients treated with angiotensin-converting enzyme inhibitors (ACE inhibitors) develop intolerance. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) can be used as an alternative treatment. OBJECTIVE In this study we aimed to evaluate the tolerability of ARBs in patients with intolerance to ACE inhibitors. DATA SOURCES The electronic databases PubMed, MEDLINE/EMBASE via Dialog, CENTRAL, and ISI Web of Knowledge were searched. STUDY SELECTION Randomized controlled trials (RCTs) evaluating ARBs in patients with intolerance to ACE inhibitors were selected. DATA SYNTHESIS Risk ratio (RR) and 95% confidence intervals (CIs) were estimated assuming the random effects method. We found 11 RCTs comparing ARBs with ACE inhibitors, diuretics, or placebo, and one RCT comparing high-dose versus low-dose ARB. RESULTS ARBs had fewer cough events versus ACE inhibitors (RR 0.37; 95% CI 0.28, 0.48). ARBs had drug discontinuation (RR 0.99; 95% CI 0.84, 1.17) and cough risk (RR 1.01; 95% CI 0.74, 1.39) rates similar to placebo. Angioedema risk with ARBs was also similar to placebo (RR 1.62; 95% CI 0.17, 15.79). Compared with placebo, hypotension (RR 2.63; 95% CI 1.77, 3.92), renal dysfunction (RR 2.07; 95% CI 1.45, 2.95) and hyperkalemia (RR 3.37; 95% CI 1.60, 7.11) were more frequent with ARBs. CONCLUSIONS ACE inhibitor rechallenge should be discouraged in patients with previous intolerance to ACE inhibitors due to a higher risk of cough. ARBs had cough and angioedema incidences similar to placebo. Despite a significantly higher incidence of hypotension, renal dysfunction and hyperkalemia, discontinuation of ARBs was similar to placebo.

Rate vs rhythm control in patients with atrial fibrillation and heart failure: A systematic review and meta-analysis of randomised controlled trials

BACKGROUND Atrial fibrillation (AF) is a common arrhythmia that can promote or worsen heart failure (HF). Our purpose was to compare the effects of rate and rhythm control in patients with atrial fibrillation and heart failure. METHODS We developed a systematic search in August 2010 through CENTRAL and MEDLINE databases to identify randomised controlled trials (RCTs) comparing rate control with rhythm control in patients with both AF and HF. We analysed mortality, hospitalisations, stroke/thromboembolic events, quality of life, and drugs adverse events. Relative risks (RR) and 95% confidence intervals (95% CI) were calculated for mortality and hospitalisations. The remaining outcomes were analysed qualitatively. RESULTS Four RCTs with a total of 2486 patients with atrial fibrillation and heart failure were identified. Mortality and stroke/thromboembolic events were not significantly different in rate and rhythm control arms [RR 1.03; 95% CI: 0.90-1.17] and [RR 1.09; 95% CI: 0.61-1.96], respectively. Hospitalisations were less frequent with rate control than with rhythm control [RR 0.92; 95% CI: 0.86-0.98; p=0.008], in 3 studies involving 2425 patients. Number needed to treat to prevent one hospitalisation was 19 patients. CONCLUSIONS In patients with AF and HF, rate control compared with rhythm control showed inferior risk of hospitalisation.

Efficacy and safety of low molecular weight heparin in patients with mechanical heart valves: systematic review and meta-analysis.

Low molecular weight heparins (LMWHs) are not approved for patients with mechanical heart valves (MHVs). However, in several guidelines, temporary LMWH off‐label use in this clinical setting is considered to be a valid treatment option. Therefore, we reviewed the efficacy and safety of LMWHs in patients with MHVs.

Copeptin for Discriminating Two-Year Mortality in Heart Failure Patients with Moderate to Severe Systolic Dysfunction

Background: Patients with heart failure and impaired systolic function may have a highly variable clinical course that renders it difficult to assess the individual prognosis. We hypothesized that ejection fraction would incompletely characterize prognosis in systolic heart failure and that biomarkers would add significant information. This study addresses the specific question whether co-peptin may add value in the evaluation of two-year prognosis in heart failure patients with known systolic dysfunction. Methods: Prospective observational cohort study in 37 patients with symptomatic chronic heart failure (classes II to IV of the NYHA classification) and moderate to severe left ventricular systolic dysfunction. We evaluated clinical, echo-cardiographic and laboratory predictors of 24-month mortality specifically assessing the role of co-peptin. Results: Six patients (16%) died during the follow-up. Patients who died had significant higher prevalence of NYHA class IV heart failure, higher blood osmolality and higher levels of NT-proBNP and co-peptin. In unvariable analysis NYHA functional class (p=0.013), serum creatinine (p=0.034), osmolality (p=0.009), NT-proBNP (p=0.013) and copeptin (p=0.003) were predictors of mortality at 24 months. Only copeptin (p=0.004) remained an independent predictor of death in Cox regression analysis. Conclusions: Our results suggest that, in patients with heart failure and impaired left ventricular systolic function, copeptin level determination may be useful for predicting mortality at two years.

P6161Cardiotoxicity in haematological diseases: are the tyrosine kinase inhibitors imatinib and nilotinib safe?

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