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Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension.

ABSTRACT: OBJECTIVES:Previous studies have demonstrated that high-dose allopurinol is able to regress left ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high-dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well-controlled blood pressure but without established cardiovascular disease. METHODS:We conducted a mechanistic proof-of-concept randomized, placebo-controlled, double-blind trial of allopurinol (600?mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow-mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress. RESULTS:Seventy-two patients were randomized into the trial. Mean baseline urate was 362.2?±?96.7??mol/l. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared with placebo (LV mass -0.37?±?6.08 versus -3.75?±?3.89?g; P?=?0.012). Oxidative stress markers (thiobarbituric acid reactive substances) were significantly higher in the allopurinol group versus placebo (0.26?±?0.85 versus -0.34?±?0.83??mol/l; P?=?0.007). Other markers of vascular function were not significantly different between the two groups. CONCLUSION:Treatment with high-dose allopurinol in normouricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be because of an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.

SUBMITTER: Gingles CR

PROVIDER: S-EPMC6855336 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension.

Gingles Christopher R CR Symon Ruth R Gandy Stephen J SJ Struthers Allan D AD Houston Graeme G MacDonald Thomas M TM Lang Chim C CC Donnan Peter T PT George Jacob J

Journal of hypertension 20191201 12

<h4>Objectives</h4>Previous studies have demonstrated that high-dose allopurinol is able to regress left ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high-dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well-controlled blood pressure but without established cardiovascular disease.<h4>Methods</h4>We conducted a mechanistic proof-of-concept randomized, placebo- ...[more]

PMID: 31268872

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Project description:BackgroundLeft ventricular hypertrophy (LVH) is commonly present in patients with hypertension (HT). According to the expert consensus document from American, angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) were recommended as 1st-line therapeutic drugs. However, none noticed the different efficacy between fat-soluble and selective β1-receptor blockers (FS-β-B) and other β-blockers on regression of LVH before. The aim of this analysis was to compare the efficacy of FS-β-B with the other 4 different classes of antihypertensive drugs (ACEI, ARBs, calcium channel blockers [CCBs], and diuretics) on regression of LVH.MethodsRelative trials were identified in the PubMed, Web of Science, OVID EBM Reviews and Cochrane databases, and the relevant papers were examined. We performed both traditional and Bayesian meta-analysis of randomized controlled trials (RCTs) about the regression of LVH. Sensitivity analysis and regression analysis were performed to explore possible sources of heterogeneity. Inconsistency analysis was performed to check whether the analysis of the trials in the network was indeed consistent.ResultsA total of 41 RCTs involving 2566 patients with HT and LVH were included in this analysis. Bayesian network meta-analysis indicated no statistically significant differences between these groups: FS-β-B and ACEI (MD, -7.09; 95% CI, -14.99, 1.27); FS-β-B and ARB (MD, -2.66; 95% Cl, -12.02, 6.31). Although FS-β-B showed greater efficacy when compared with diuretic (MD, 13.04; 95% CI, 3.38, 22.59) or CCB (MD, 10.90; 95% CI, 1.98, 19.49). The probabilities of being among the most efficacious treatments were: FS-β-B (72%), ARB (27%), ACEI (0.01%), CCB (0.00%), and diuretic (0.00%).ConclusionEvidence from our analysis reveals that FS-β-B have potential to become 1st-line therapeutic drugs in HT and LVH patients. However, the real efficacy of FS-β-B on regression of LVH should be confirmed by further large, high quality trials considering the limitation of the study number.

Project description:BackgroundCardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD.MethodsThe primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined.ResultsThe meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16.ConclusionsThese results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.

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Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension.

Publications

Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension.

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