scholarly journals Effect of antihypertensive drug treatment on long-term blood pressure reduction: An individual patient-level data meta-analysis of 352,744 Participants from 51 large-scale randomised clinical trials

2021 ◽  
Author(s):  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Antihypertensive Treatment ◽  
Large Scale ◽  
Meta Analysis ◽  
Level Data ◽  
Wide Range

ABSTRACTObjectivesEvidence from randomised trials on long-term blood pressure (BP) reduction from pharmacologic treatment is limited. To investigate the effects of antihypertensive drugs on long-term BP change and examine its variation over time and among people with different clinical characteristicsDesignIndividual participant-level data meta-analysisSetting and data sourceThe Blood Pressure Lowering Treatment Trialists’ Collaboration involving 51 large-scale long-term randomised clinical trialsParticipants352,744 people (42% women) with mean age of 65 years and mean baseline systolic/diastolic BP of 152/87 mmHg, of whom 18% were current smokers, 50% had cardiovascular disease, 29% had diabetes, and 72% were taking antihypertensive treatment at baselineInterventionPharmacological BP-lowering treatmentOutcomeDifference in longitudinal changes in systolic and diastolic BP between randomised treatment arms over an average follow-up of four yearsResultDrugs were effective in lowering BP, with the maximum effect becoming apparent after 12-month follow-up and with gradual attenuation towards later years. Based on measures taken ≥12 months post-randomisation, more intense BP-lowering treatment reduced systolic/diastolic BP (95% confidence interval) by −11.2 (−11.4 to −11.0)/−5.6 (−5.8 to −5.5) mmHg than less intense treatment; active treatment by −5.1 (−5.3 to −5.0)/−2.3 (−2.4 to −2.2) mmHg lower than placebo, and active arm by −1.4 (−1.5 to −1.3)/−0.6 (−0.7 to −0.6) mmHg lower than the control arm for drug class comparison trials. BP reductions were consistently observed across a wide range of baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes, and prior antihypertensive treatment use.ConclusionPharmacological agents were effective in lowering long-term BP among individuals with a wide range of characteristics, but the net between-group reductions were modest, which is partly attributable to the intended trial goals.

Stratified effects of blood pressure-lowering treatment on long-term blood pressure: an individual patient-level meta-analysis involving 50 randomised trials and 334,219 participants

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Canoy ◽  
E Copland ◽  
R Ramakrishnan ◽  
A.C Pinho-Gomes ◽  
M Nazarzadeh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Controlled Trials ◽  
Funding Source ◽  
Individual Patient Level ◽  
Patient Level

Abstract Background Meta-analyses of randomised controlled trials (RCT) have shown the efficacy of pharmacologic lowering of blood pressure (BP) in reducing cardiovascular disease (CVD) risk. While efficacy has been shown across important patient characteristics, meta-analysis based on aggregate data could not fully account for potential sources of variation due to individual-level characteristics. Moreover, it is unclear if any variation in treatment effects due to patient characteristics are reflected in differential effects of BP-lowering treatment on long-term BP according to these characteristics. Purpose We determined the effects of BP-lowering treatment on repeated measures of blood pressure, identified trial- and participant-level sources of heterogeneity, and examined consistency of these BP-lowering effects across different patient characteristics. Methods We conducted an individual patient-level data meta-analysis (N=50 trials) using one-stage approach. We classified trials according to trial design: drug comparison (N=28), placebo-controlled (N=21) and BP-lowering intensity (N=8) trials. We fitted mixed models with fixed treatment effects and fixed time effect, random intercepts at trial and participant level, and a random slope for time at participant level. We adjusted for age, sex and baseline BP (except when used as stratification factor). We used likelihood ratio test and Akaike information criterion to compare models. Results This meta-analysis included 334,219 (42% women) participants. At baseline, mean age=65 (SD=9) years, among whom 18% were current smokers, 47% had cardiovascular disease, 29% had diabetes, and 73% were previously on BP-lowering medication. Participants had an average of 8 BP measurements over 4 years of mean follow-up. For drug comparison trials, mean differences (95% confidence interval) in systolic BP (SBP) and diastolic BP (DBP) between comparison arms were 1.3 (1.2 to 1.3) mmHg and 0.5 (0.5 to 0.5) mmHg, respectively; for placebo-controlled trials, the SBP and DBP differences were 4.2 (4.0 to 4.3) mmHg and 1.9 (1.9 to 2.0) mmHg, respectively; and for BP-lowering intensity trials, the SBP and DBP differences were 8.2 (8.0 to 8.4) mmHg and 3.7 (3.6 to 3.9) mmHg, respectively. However, BP reduction differed by duration of follow-up, type of trial. In particular, for placebo-controlled and BP-intensity trials, heterogeneity in BP reductions according to patient characteristics such as baseline BP, age, sex, prior CVD, diabetes and non-randomised anti-hypertensive use were observed. Conclusion This study shows the role of pharmacologic agents in effectively reducing long-term BP across individuals with a wide range of characteristics. The magnitude of BP reduction varied by several patient characteristics. This might have implications for investigation and explanation of any differential effects of BP treatment on major clinical outcomes. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): British Heart Foundation; NIHR Oxford Biomedial Research Centre

Large-scale randomized evidence: Trials and meta-analyses of trials

2020 ◽  
pp. 51-66
Author(s):  
Colin Baigent ◽  
Richard Peto ◽  
Richard Gray ◽  
Natalie Staplin ◽  
Sarah Parish ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Large Scale ◽  
Meta Analysis ◽  
False Negative ◽  
Premature Deaths ◽  
Common Causes ◽  
The Common ◽  
Meta Analyses ◽  
Positive Results

Clinical trials generally need to be able to detect or to refute realistically moderate (but still worthwhile) differences between treatments in long-term disease outcome. Large-scale randomized evidence should be able to detect such effects, but medium-sized trials or medium-sized meta-analyses can, and often do, yield false-negative or exaggeratedly positive results. Hundreds of thousands of premature deaths each year could be avoided by seeking appropriately large-scale randomized evidence about various widely practicable treatments for the common causes of death, and by disseminating this evidence appropriately. This chapter takes a look at the use of large-scale randomized evidence—produced from trials and meta-analysis of trials—and how this data should be handled in order to produce accurate result.

P4414Effects of lorcaserin on the cardiometabolic risk factors in overweight or obese patients: a systematic review and meta-analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H H Kuo ◽  
M E Liu ◽  
P L Lin ◽  
L.Y.-M Liu
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Meta Analysis ◽  
Obese Patients ◽  
Serotonin 2C Receptor ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
Search Terms

Abstract Introduction Lorcaserin is a selective serotonin 2c receptor agonist approved as an anti-obesity agent. The additional cardiometabolic benefits associated with lorcaserin have not been conclusively established. Purpose To examine the effects of lorcaserin on blood pressure, heart rate and other metabolic parameters in overweight or obese patients from randomized controlled clinical trials (RCTs). Methods A literature search was conducted on PubMed, EMBASE, and Cochrane Central using search terms: “lorcaserin”, “Belviq”, and “randomized controlled trials” without language restrictions. RCTs with a follow-up period of at least 24 weeks were included for the meta-analysis. Results Five studies with 9349 patients in the lorcaserin group and 9370 patients in the placebo group were included. Compared with placebo, lorcaserin not only reduced weight (mean difference [MD] = −3.03 kg, 95% CI: −3.42, −2.63, P<0.ehz745.08171, I2 =68%), waist circumference (MD=−2.27 cm, 95% CI: −2.71, −1.83, P<0.ehz745.08171, I2=57%) and BMI (MD=−1.11 kg/m2, 95% CI: −1.27, −0.96, P<0.ehz745.08171, I2=68%), but also improved SBP (MD=−0.75 mmHg, 95% CI: −1.12, −0.38, P<0.0001, I2=0%), DBP (MD=−0.70 mmHg, 95% CI: −0.93, −0.48, P<0.ehz745.08171, I2=0%), heart rate (MD=−0.94 bpm, 95% CI: −1.28, −0.60, P<0.ehz745.08171, I2=0%), LDL (MD=−1.47 mg/dL, 95% CI: −2.21, −0.74, P<0.0001, I2=0%), HDL (MD=0.55 mg/dL, 95% CI: 0.08, 1.01, P=0.02, I2=18%), triglycerides (MD=−8.71 mg/dL, 95% CI: −12.14, −5.28, P<0.ehz745.08171, I2=71%), and fasting plasma glucose (MD=−5.69 mg/L, 95% CI: −9.5, −1.87, P=0.003, I2=93%). Our findings support that lorcaserin has consistent and favourable effects on blood pressure, heart rate, and all criteria of metabolic syndrome. Summary of lorcaserin effects Conclusion Lorcaserin improved all cardiometabolic parameters modestly in addition to its weight loss effect in overweight or obese patients. More research is needed to determine its long-term cardiovascular benefits.

scholarly journals Polyphenol in reducing cardiovascular outcomes in adult: A Rapid Review and Meta Analysis

2021 ◽  
Vol 7 (1) ◽  
pp. 36-47
Author(s):  
Arditya Damar Kusuma ◽  
Anggoro Budi Hartopo
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Diastolic Blood Pressure ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Risk Of Bias ◽  
Surrogate Endpoints ◽  
Men And Women

Abstract Objectives This review has an objective to determine the effectiveness of polyphenol intervention for the primary prevention of cardiovascular disease events and others surrogate endpoint which may correlate with cardiovascular disease events Data Sources These electronic databases were used to search the appropriate trials: MEDLINE (OvidSP, 1946 to March week 2 2020); The Cochrane Central Register of Controlled Trials (CENTRAL,week 2 March 2020). We only used English language trials that were available on these two databases. Review Methods We chose randomized controlled trials both in healthy or having high risk of cardiovascular diseases. Polyphenol as intervention was described as any food or drink that has polyphenol or its derived substance as main content. Placebo or no intervention is the comparison group. Cardiovascular clinical events and surrogate endpoints or cardiovascular disease risk factors are included in the outcome. Revman 5.5 software was used to analyze all the trials and to assess the risk of bias each trial. We selected random or fixed effects depend on the heterogeneity between trials in the meta analysis. Results Seven trials were included with 49200 participants randomized. Heterogeneity was shown between trials regarding the characteristic of participants, types of polyphenol intervention, and follow up periods. Cardiovascular event outcomes are only available in one trial (Howard et al 2006), with the intervention not clearly defined as polyphenol but increasing fruit and grain consumption. This trial shows no evidence was shown on fatal and non-fatal cardiovascular outcome by consuming more fruit and grain with 8 years mean of follow up. By analyzing remaining trials, which provide surrogate endpoints or cardiovascular risk factors, there is no evidence that polyphenol intervention reduce systolic and diastolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol level, and triglyceride level. However, reduction total cholesterol level was shown from the baseline (MD -5.41 mg/dl, 95% CI -8.21 to -2.62, P=0.0001). Subgroup analyses were done with dividing the trials that involve women only and both men and women. This analysis shows the reduction of both systolic (MD -2.78 mmHg, 95% CI -5.47 to -0.08, P=0.04) and diastolic blood pressure (MD -2.59 mmHg, 95% CI -4.84 to -0.34, P=0.02) in trials involving both men and women. A sensitivity analysis was done by excluding the trials with risk of bias with no different results effect. Moreover, not any trials reported adverse events of polyphenol. Author’s Conclusion Due to the limitation evidence or trial available, we could not obtain meta analysis on the primary outcome. Nevertheless, this review suggests that polyphenol intervention does show favorable effect on surrogate endpoints which was total cholesterol levels. Besides, systolic blood pressure and diastolic blood pressure in trials which involves both men and women also shown an improvement. The high heterogeneity in this review also suggests that more evidence are needed to assess the effectiveness of polyphenol intervention in reducing cardiovascular event outcomes and risk factors in the future.

P1548Long-term past, current and usual systolic blood pressure and incident cardiovascular disease: risk prediction using large-scale, routinely recorded clinical data

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J R Ayala Solares ◽  
D Canoy ◽  
F E D Raimondi ◽  
Y Zhu ◽  
A Hassaine ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Systolic Blood Pressure ◽  
Risk Prediction ◽  
Large Scale ◽  
Predictive Performance ◽  
Weighted Mean ◽  
Age Cohort ◽  
Mean Time

Abstract Background The impact of long-term exposure to elevated systolic blood pressure (SBP) on future cardiovascular disease (CVD) in “real-world” settings, and its relevance to risk prediction, are less investigated. Purpose To examine the risk of incident CVD in relation to long-term past, current, and usual SBP, and compare their predictive performance, using evidence from large-scale electronic health records (EHR). Methods Using data extracted from UK primary care linked EHR, we applied a landmark cohort study design, by including patients aged 40 (N≈64,000), 50 (N≈80,000) and 60 (N≈67,000) years (y) at study entry who had recorded SBP and with no prior CVD or previous antihypertensive or lipid-lowering prescriptions at baseline. We estimated past SBP (mean, time-weighted mean, and variability recorded up to 10 years prior to baseline) and usual SBP (correcting current values for past time-dependent SBP variability). We used Cox regression to estimate hazard ratio (HR), and applied Bayesian analysis within a machine learning framework in developing and validating models. To evaluate predictive performance of the models, we used discrimination (area under the curve [AUC]) and calibration metrics. The outcome was incident CVD (first hospitalisation for or death from coronary heart disease or stroke/transient ischaemic attack). Analyses were conducted separately for each age cohort. Results After a mean follow-up of 8 years, the numbers of patients who developed incident CVD were over 1000 (40y), 3000 (50y) and 5000 (60y). Higher past, current and usual SBP values were separately and independently associated with increased incident CVD risk. Per 20-mmHg rise in SBP, the HR (95% credible interval [CI]) for current SBP for ages 40, 50 and 60 years were 1.18 (1.08 to 1.26), 1.22 (1.18 to 1.30) and 1.22 (1.19 to 1.24); the corresponding HR were stronger in magnitude for past SBP (mean and time-weighted mean) and usual SBP (HR ranged from: 40y=1.31 to 1.41, 50y=1.39 to 1.45 and 60y=1.32 to 1.48). For each age cohort, the AUC (95% CI) for the model that included current SBP, sex, smoking, deprivation, diabetes and lipid profile in the validation sample were: 40y=0.739 (0.730 to 0.746), 50y=0.750 (0.716 to 0.810), and 60y=0.647 (0.642 to 0.658). Adding past SBP mean, time-weighted mean or variability to this model were associated with modest increases in the AUC and all models showed good calibration. Small improvements in the AUC were similarly observed when evaluating models separately for men and women within each age cohort. Conclusion Using multiple SBP recordings from patients' EHR showed stronger associations with incident CVD than a single SBP measurement, but their addition to multivariate risk prediction models had negligible effects on model performance. Acknowledgement/Funding Oxford Martin School and National Institute for Health Research Oxford Biomedical Research Centre

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