Dataset Information

Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials.

ABSTRACT:

Background

Patients undergoing dialysis have a substantially increased risk of cardiovascular mortality and morbidity. Although several trials have shown the cardiovascular benefits of lowering blood pressure in the general population, there is uncertainty about the efficacy and tolerability of reducing blood pressure in patients on dialysis. We did a systematic review and meta-analysis to assess the effect of blood pressure lowering in patients on dialysis.

Methods

We systematically searched Medline, Embase, and the Cochrane Library database for trials reported between 1950 and November, 2008, without language restriction. We extracted a standardised dataset from randomised controlled trials of blood pressure lowering in patients on dialysis that reported cardiovascular outcomes. Meta-analysis was done with a random effects model.

Findings

We identified eight relevant trials, which provided data for 1679 patients and 495 cardiovascular events. Weighted mean systolic blood pressure was 4.5 mm Hg lower and diastolic blood pressure 2.3 mm Hg lower in actively treated patients than in controls. Blood pressure lowering treatment was associated with lower risks of cardiovascular events (RR 0.71, 95% CI 0.55-0.92; p=0.009), all-cause mortality (RR 0.80, 0.66-0.96; p=0.014), and cardiovascular mortality (RR 0.71, 0.50-0.99; p=0.044) than control regimens. The effects seem to be consistent across a range of patient groups included in the studies.

Interpretation

Treatment with agents that lower blood pressure should routinely be considered for individuals undergoing dialysis to reduce the very high cardiovascular morbidity and mortality rate in this population.

SUBMITTER: Heerspink HJ

PROVIDER: S-EPMC2659734 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Publications

Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials.

Heerspink Hiddo J Lambers HJ Ninomiya Toshiharu T Zoungas Sophia S de Zeeuw Dick D Grobbee Diederick E DE Jardine Meg J MJ Gallagher Martin M Roberts Matthew A MA Cass Alan A Neal Bruce B Perkovic Vlado V

Lancet (London, England) 20090225 9668

<h4>Background</h4>Patients undergoing dialysis have a substantially increased risk of cardiovascular mortality and morbidity. Although several trials have shown the cardiovascular benefits of lowering blood pressure in the general population, there is uncertainty about the efficacy and tolerability of reducing blood pressure in patients on dialysis. We did a systematic review and meta-analysis to assess the effect of blood pressure lowering in patients on dialysis.<h4>Methods</h4>We systematica ...[more]

PMID: 19249092

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Project description:ObjectiveTo define the cardiovascular effects of lowering blood pressure in people with chronic kidney disease.DesignCollaborative prospective meta-analysis of randomised trials.Data sources and eligibilityParticipating randomised trials of drugs to lower blood pressure compared with placebo or each other or that compare different blood pressure targets, with at least 1000 patient years of follow-up per arm.Main outcome measuresMajor cardiovascular events (stroke, myocardial infarction, heart failure, or cardiovascular death) in composite and individually and all cause death.Participants26 trials (152,290 participants), including 30,295 individuals with reduced estimated glomerular filtration rate (eGFR), which was defined as eGFR <60 mL/min/1.73 m(2).Data extractionIndividual participant data were available for 23 trials, with summary data from another three. Meta-analysis according to baseline kidney function was performed. Pooled hazard ratios per 5 mm Hg lower blood pressure were estimated with a random effects model.ResultsCompared with placebo, blood pressure lowering regimens reduced the risk of major cardiovascular events by about a sixth per 5 mm Hg reduction in systolic blood pressure in individuals with (hazard ratio 0.83, 95% confidence interval 0.76 to 0.90) and without reduced eGFR (0.83, 0.79 to 0.88), with no evidence for any difference in effect (P=1.00 for homogeneity). The results were similar irrespective of whether blood pressure was reduced by regimens based on angiotensin converting enzyme inhibitors, calcium antagonists, or diuretics/β blockers. There was no evidence that the effects of different drug classes on major cardiovascular events varied between patients with different eGFR (all P>0.60 for homogeneity).ConclusionsBlood pressure lowering is an effective strategy for preventing cardiovascular events among people with moderately reduced eGFR. There is little evidence from these overviews to support the preferential choice of particular drug classes for the prevention of cardiovascular events in chronic kidney disease.

Project description:ImportanceHigh blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated.ObjectiveTo assess the association between BP lowering treatment and death and CVD at different BP levels.Data sourcesPrevious systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017.Study selectionRandomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included.Data extraction and synthesisData were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines.Main outcomes and measuresPrespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease.ResultsSeventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07).Conclusions and relevancePrimary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.

Project description:ObjectiveTo determine all cause mortality and deaths from cardiovascular events related to intensive glucose lowering treatment in people with type 2 diabetes.DesignMeta-analysis of randomised controlled trials.Data sourcesMedline, Embase, and the Cochrane database of systematic reviews.Study selectionRandomised controlled trials that assessed the effect of intensive glucose lowering treatment on cardiovascular events and microvascular complications in adults (≥ 18 years) with type 2 diabetes.Data extractionPrimary end points were all cause mortality and death from cardiovascular causes. Secondary end points were severe hypoglycaemia and macrovascular and microvascular events. Synthesis of results Results are reported as risk ratios with 99% confidence intervals. Statistical heterogeneity between trials was assessed with χ(2), τ(2), and I(2) statistics. A fixed effect model was used to assess the effect on the outcomes of intensive glucose lowering versus standard treatment. The quality of clinical trials was assessed by the Jadad score.Results13 studies were included. Of 34,533 patients, 18,315 received intensive glucose lowering treatment and 16,218 standard treatment. Intensive treatment did not significantly affect all cause mortality (risk ratio 1.04, 99% confidence interval 0.91 to 1.19) or cardiovascular death (1.11, 0.86 to 1.43). Intensive therapy was, however, associated with reductions in the risk of non-fatal myocardial infarction (0.85, 0.74 to 0.96, P<0.001), and microalbuminuria (0.90, 0.85 to 0.96, P<0.001) but a more than twofold increase in the risk of severe hypoglycaemia (2.33, 21.62 to 3.36, P<0.001). Over a treatment period of five years, 117 to 150 patients would need to be treated to avoid one myocardial infarction and 32 to 142 patients to avoid one episode of microalbuminuria, whereas one severe episode of hypoglycaemia would occur for every 15 to 52 patients. In analysis restricted to high quality studies (Jadad score >3), intensive treatment was not associated with any significant risk of reductions but resulted in a 47% increase in risk of congestive heart failure (P<0.001).ConclusionsThe overall results of this meta-analysis show limited benefits of intensive glucose lowering treatment on all cause mortality and deaths from cardiovascular causes. We cannot exclude a 9% reduction or a 19% increase in all cause mortality and a 14% reduction or a 43% increase in cardiovascular death. The benefit:risk ratio of intensive glucose lowering treatment in the prevention of macrovascular and microvascular events remains uncertain. The harm associated with severe hypoglycaemia might counterbalance the potential benefit of intensive glucose lowering treatment. More double blind randomised controlled trials are needed to establish the best therapeutic approach in people with type 2 diabetes.

Project description:BackgroundRandomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline.Methods and findingsThe study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF.ConclusionsIn this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in individuals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF.

Project description:BackgroundClinical practice guidelines have traditionally recommended blood pressure treatment based primarily on blood pressure thresholds. In contrast, using predicted cardiovascular risk has been advocated as a more effective strategy to guide treatment decisions for cardiovascular disease (CVD) prevention. We aimed to compare outcomes from a blood pressure-lowering treatment strategy based on predicted cardiovascular risk with one based on systolic blood pressure (SBP) level.Methods and findingsWe used individual participant data from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) from 1995 to 2013. Trials randomly assigned participants to either blood pressure-lowering drugs versus placebo or more intensive versus less intensive blood pressure-lowering regimens. We estimated 5-y risk of CVD events using a multivariable Weibull model previously developed in this dataset. We compared the two strategies at specific SBP thresholds and across the spectrum of risk and blood pressure levels studied in BPLTTC trials. The primary outcome was number of CVD events avoided per persons treated. We included data from 11 trials (47,872 participants). During a median of 4.0 y of follow-up, 3,566 participants (7.5%) experienced a major cardiovascular event. Areas under the curve comparing the two treatment strategies throughout the range of possible thresholds for CVD risk and SBP demonstrated that, on average, a greater number of CVD events would be avoided for a given number of persons treated with the CVD risk strategy compared with the SBP strategy (area under the curve 0.71 [95% confidence interval (CI) 0.70-0.72] for the CVD risk strategy versus 0.54 [95% CI 0.53-0.55] for the SBP strategy). Compared with treating everyone with SBP ≥ 150 mmHg, a CVD risk strategy would require treatment of 29% (95% CI 26%-31%) fewer persons to prevent the same number of events or would prevent 16% (95% CI 14%-18%) more events for the same number of persons treated. Compared with treating everyone with SBP ≥ 140 mmHg, a CVD risk strategy would require treatment of 3.8% (95% CI 12.5% fewer to 7.2% more) fewer persons to prevent the same number of events or would prevent 3.1% (95% CI 1.5%-5.0%) more events for the same number of persons treated, although the former estimate was not statistically significant. In subgroup analyses, the CVD risk strategy did not appear to be more beneficial than the SBP strategy in patients with diabetes mellitus or established CVD.ConclusionsA blood pressure-lowering treatment strategy based on predicted cardiovascular risk is more effective than one based on blood pressure levels alone across a range of thresholds. These results support using cardiovascular risk assessment to guide blood pressure treatment decision-making in moderate- to high-risk individuals, particularly for primary prevention.

Project description:BackgroundCommunication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making.ObjectivesTo quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days DESIGN: Post hoc analysis of the Systolic Blood Pressure Intervention Trial PARTICIPANTS: A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130-180 mmHg and elevated cardiovascular risk INTERVENTIONS: Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg) MAIN MEASURES: Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years KEY RESULTS: The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, -15.0 [-56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, -22.7 [-51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, -14.8 [-35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event-free days than the standard treatment group (difference, -28.5 [-40.3, -16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, -15.5 [-46.6, 15.7] days) and self-rated health (excellent: difference, -12.9 [-45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001).ConclusionsOver 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated.Trial registrationClinicalTrials.gov Registration: NCT01206062.

Project description:ObjectiveTo determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination.DesignMeta-analysis of 354 randomised double blind placebo controlled trials of thiazides, beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium channel blockers in fixed dose.Subjects40,000 treated patients and 16,000 patients given placebo.Main outcome measuresPlacebo adjusted reductions in systolic and diastolic blood pressure and prevalence of adverse effects, according to dose expressed as a multiple of the standard (recommended) doses of the drugs.ResultsAll five categories of drug produced similar reductions in blood pressure. The average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) at half standard dose. The drugs reduced blood pressure from all pretreatment levels, more so from higher levels; for a 10 mm Hg higher blood pressure the reduction was 1.0 mm Hg systolic and 1.1 mm Hg diastolic greater. The blood pressure lowering effects of different categories of drugs were additive. Symptoms attributable to thiazides, beta blockers, and calcium channel blockers were strongly dose related; symptoms caused by ACE inhibitors (mainly cough) were not dose related. Angiotensin II receptor antagonists caused no excess of symptoms. The prevalence of symptoms with two drugs in combination was less than additive. Adverse metabolic effects (such as changes in cholesterol or potassium) were negligible at half standard dose.ConclusionsCombination low dose drug treatment increases efficacy and reduces adverse effects. From the average blood pressure in people who have strokes (150/90 mm Hg) three drugs at half standard dose are estimated to lower blood pressure by 20 mm Hg systolic and 11 mm Hg diastolic and thereby reduce the risk of stroke by 63% and ischaemic heart disease events by 46% at age 60-69.

Project description:BackgroundPrevious studies have demonstrated that intensive blood pressure (BP) lowering treatment reduces the risk of all-cause mortality and provides greater vascular protection for patients with hypertension. Whether intensive BP lowering treatment is associated with such benefits in patients with type 2 diabetes mellitus remain unknown. We aimed to clarify these benefits by method of meta-analysis.MethodsThe PubMed, EMBASE, Science Citation Index and Cochrane Library databases were searched to identify randomized controlled trials (RCT) that fulfilled study inclusion criteria. Two investigators independently extracted and summarized the relevant data of the included trials. Random-effects model was applied to calculate the estimates of all effect measures.ResultsWe included 16 RCTs and our meta-analysis showed that intensive BP lowering treatment vs less intensive BP lowering treatment resulted in significant reductions in the all-cause mortality risk [relative risk (RR), 0.82; 95% CI, 0.70-0.96], major CV events (RR, 0.82; 95% CI, 0.73-0.92, MI (RR, 0.86; 95% CI, 0.77-0.96), stroke (RR, 0.72; 95% CI, 0.60-0.88, CV death (RR, 0.73; 95% CI, 0.58-0.92) and albuminuria progression (RR, 0.91 95% CI, 0.84-0.98). However, intensive BP lowering treatment had no clear effect on non-CV death (RR, 0.97; 95% CI, 0.79-1.20), heart failure (HF) (RR, 0.88; 95% CI, 0.71-1.08) or end-stage kidney disease (ESKD) (RR, 1.00; 95% CI, 0.75-1.33). Subgroup analysis showed that the reduction in all cause-mortality was consistent across most patient groups, and intensive BP lowering treatment had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. However, the benefit differed in patients with different CV risk (≥10%: RR, 0.77, 95%CI, 0.64-0.91; <10%: RR, 1.04, 95%CI, 0.84-1.29; Phetero = 0.028).ConclusionsOur data indicate that intensive BP lowering treatment provides greater benefits than less intensive treatment among patients with type 2 diabetes mellitus. Further studies are required to more clearly evaluate the benefits and harms of BP targets below those currently recommended with intensive BP lowering treatment.

Dataset Information

Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials.

Background

Methods

Findings

Interpretation

Publications

Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials.

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