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Oral Antihypertensives for Nonsevere Pregnancy Hypertension: Systematic Review, Network Meta- and Trial Sequential Analyses.
Bone, JN, Sandhu, A, Abalos, ED, Khalil, A, Singer, J, Prasad, S, Omar, S, Vidler, M, von Dadelszen, P, Magee, LA
Hypertension (Dallas, Tex. : 1979). 2022;(3):614-628
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Abstract
BACKGROUND We aimed to address which antihypertensives are superior to placebo/no therapy or another antihypertensive for controlling nonsevere pregnancy hypertension and provide future sample size estimates for definitive evidence. METHODS Randomized trials of antihypertensives for nonsevere pregnancy hypertension were identified from online electronic databases, to February 28, 2021 (registration URL: https://www.crd.york.ac.uk/PROSPERO/; unique identifier: CRD42020188725). Our outcomes were severe hypertension, proteinuria/preeclampsia, fetal/newborn death, small-for-gestational age infants, preterm birth, and admission to neonatal care. A Bayesian random-effects model generated estimates of direct and indirect treatment comparisons. Trial sequential analysis informed future trials needed. RESULTS Of 1246 publications identified, 72 trials were included; 61 (6923 women) were informative. All commonly prescribed antihypertensives (labetalol, other β-blockers, methyldopa, calcium channel blockers, and mixed/multi-drug therapy) versus placebo/no therapy reduced the risk of severe hypertension by 30% to 70%. Labetalol decreased proteinuria/preeclampsia (odds ratio, 0.73 [95% credible interval, 0.54-0.99]) and fetal/newborn death (odds ratio, 0.54 [0.30-0.98]) compared with placebo/no therapy, and proteinuria/preeclampsia compared with methyldopa (odds ratio, 0.66 [0.44-0.99]) and calcium channel blockers (odds ratio, 0.63 [0.41-0.96]). No other differences were identified, but credible intervals were wide. Trial sequential analysis indicated that 2500 to 10 000 women/arm (severe hypertension or safety outcomes) to >15 000/arm (fetal/newborn death) would be required to provide definitive evidence. CONCLUSIONS In summary, all commonly prescribed antihypertensives in pregnancy reduce the risk of severe hypertension, but labetalol may also decrease proteinuria/preeclampsia and fetal/newborn death. Evidence is lacking for many other safety outcomes. Prohibitive sample sizes are required for definitive evidence. Real-world data are needed to individualize care.
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Antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia: A systemic review and meta-analysis of randomized studies.
Lee, S, Yang, S, Chang, MJ
PloS one. 2021;(11):e0260391
Abstract
Some studies have suggested the antihypertensive effects of statins, a class of lipid-lowering agents, particularly in patients with hypertension. However, the evidence for the role of statins in blood pressure (BP) lowering is controversial, and no meta-analysis of rosuvastatin therapy has been conducted to assess its BP-lowering effects. Therefore, the aim of this meta-analysis of randomized controlled trials (RCTs) was to investigate the effects of rosuvastatin on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with hypertension. We systematically searched the electronic databases MEDLINE, EMBASE, and Cochrane Library to identify RCTs in which patients were assigned to groups of rosuvastatin plus antihypertensive agents vs. antihypertensive agents. The three authors independently selected the studies, extracted data, and assessed methodological quality. We included five RCTs in this meta-analysis with 288 patients treated with rosuvastatin and 219 patients without rosuvastatin. The mean DBP in the rosuvastatin group was significantly lower than that in the non-rosuvastatin group by -2.12 mmHg (95% confidence interval (CI) -3.72 to -0.52; Pfixed-effects model = 0.009; I2 = 0%, Pheterogeneity = 0.97). Rosuvastatin treatment also lowered the mean SBP compared with the non-rosuvastatin treatment by -2.27 mmHg, but not significantly (95% CI - 4.75 to 0.25; Pfixed-effects model = 0.08; I2 = 0%, Pheterogeneity = 0.82). In this study, we reviewed the antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia. We demonstrated a modest significant reduction of DBP and a trend toward a lowered SBP in patients with hypertension with rosuvastatin therapy. Rosuvastatin could be beneficial to control hypertension and, consequently, contribute toward reducing the risk of cardiovascular events in patients with hypertension and dyslipidemia.
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The effects of capsinoids and fermented red pepper paste supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials.
Amini, MR, Sheikhhossein, F, Bazshahi, E, Hajiaqaei, M, Shafie, A, Shahinfar, H, Azizi, N, Eghbaljoo Gharehgheshlaghi, H, Naghshi, S, Fathipour, RB, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1767-1775
Abstract
BACKGROUND & AIMS The present systematic review and meta-analysis were conducted to investigate the effects of capsinoids and fermented red pepper paste (FRPP) supplementation on Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP). METHODS Relevant studies, published up to May 2020, were searched through PubMed/Medline, Scopus, ISI Web of Science, Embase, and Google Scholar. All randomized clinical trials investigating the effect of capsinoids and FRPP supplementation on blood pressure including SBP and DBP were included. RESULTS Out of 335 citations, 7 trials that enrolled 363 subjects were included. Capsinoids and FRPP resulted in significant reduction in DBP (Weighted mean differences (WMD): -1.90 mmHg; 95% CI, -3.72 to -0.09, P = 0.04) but no significant change in SBP (WMD: 0.55 mmHg, 95% CI: -1.45, 2.55, P = 0.588). FRPP had a significant reduction in SBP. Greater effects on SBP were detected in trials, lasted ≥12 weeks, and sample size >50. Capsinoids with dosage ≤200 and FRPP with dosage of 11.9 g significantly decreased DBP. CONCLUSION Overall, these data suggest that supplementation with FRPP may play a role in improving SBP and DBP but for capsinoids no effects detected in this analysis on SBP and DBP.
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Nebivolol for the Treatment of Essential Systemic Arterial Hypertension: A Systematic Review and Meta-Analysis.
Seleme, VB, Marques, GL, Mendes, AEM, Rotta, I, Pereira, M, Júnior, EL, da Cunha, CLP
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2021;(2):165-180
Abstract
INTRODUCTION Cardiovascular diseases are the main cause of mortality worldwide, and systemic arterial hypertension is associated with a large number of these cases. The objective of health professionals and health policies should be searching for the best therapeutics to control this disease. A recent consensus indicated that β-blockers have recently lost their place in initial indications for the treatment of systemic arterial hypertension and are now more indicated for the treatment of hypertension in association with other clinical situations such as angina, heart failure and arrhythmia; however, it is known that this approach was based on studies that evaluated older β-blockers such as atenolol. OBJECTIVE The main objective of this study was to perform a systematic review with subsequent meta-analysis on the use of nebivolol for hypertensive disease treatment, comparing it with drugs of the main antihypertensive classes. METHODS This systematic review was based on a search of the MEDLINE (via Pubmed), Scopus, Cochrane, International Pharmaceuticals Abstracts (IPA), and Lilacs databases for randomized and double-blind clinical trials. In addition, we also searched for gray literature studies, to 31 July 2015. Next, a cumulative meta-analysis was performed, with studies being added in a sequential manner, evaluating their impact on the combined effect. For this project, we only meta-analyzed direct comparisons of random effect. RESULTS Overall, 981 clinical trials were included in this systematic review. After careful analysis, 34 randomized and double-blind clinical trials were included to investigate the efficacy of nebivolol on systolic (SBP) and diastolic blood pressure (DBP) control and adverse effects. The study population comprised 12,465 patients with systemic arterial hypertension (SAH) aged between 18 and 85 years; 17% of subjects were of Black ethnicity, approximately 55% were men, and almost 10% had diabetes. In SBP management, nebivolol was superior to other β-blockers and diuretics and showed no difference in efficacy when compared with angiotensin receptor blockers or calcium channel blockers. There were insufficient studies on angiotensin-converting enzyme inhibitors for adequate comparison of both SBP and DBP control. For DBP control, nebivolol was more efficient than other β-blockers, angiotensin receptor blockers, diuretics, and calcium channel blockers. DISCUSSION Nebivolol is a third-generation β-blocker with additional capabilities to improve blood pressure levels in patients with arterial hypertension, because it acts by additional mechanisms such as endothelium-dependent vasodilation associated with L-arginine and oxide nitric acid, nitric oxide activity on smooth muscle cells, decreasing platelet aggregation, and leukocyte adhesion in the endothelium, decreasing oxidative stress. Although nebivolol has shown good results in controlling hypertension in this study (with few adverse events when compared with placebo treatment) and has an unquestionable benefit in individuals with heart failure (mainly with reduced ejection fraction), there is a lack of studies proving the benefit of this drug for controlling hypertension and reducing clinical outcomes such as cardiovascular (or general) mortality, acute myocardial infarction, or stroke. CONCLUSIONS Nebivolol demonstrated at least similar control of blood pressure levels in hypertensive individuals when compared with drugs of the most used classes. In addition, in relation to the control of arterial hypertension, studies with clinical outcomes should be performed to ensure the use of this drug in detriment to others with these well-established results.
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Quality of life of patients with pulmonary arterial hypertension: a meta-analysis.
Sarzyńska, K, Świątoniowska-Lonc, N, Dudek, K, Jonas, K, Kopeć, G, Gajek, J, Jankowska-Polańska, B
European review for medical and pharmacological sciences. 2021;(15):4983-4998
Abstract
OBJECTIVE Pulmonary arterial hypertension (PAH) is a rare condition, with an incidence of 15-50 cases per million annually. Available studies demonstrate that despite the longer survival of PAH patients, their quality of life (QoL) deteriorates as the condition progresses. Consequently, the goals of PAH therapy have expanded from increasing survival to improving health-related quality of life. The objective of this systematic review and meta-analysis was to summarize the available evidence about the level of QoL in patients with PAH. MATERIALS AND METHODS A systematic search was performed using the Cochrane guidelines for conducting meta-analysis following the PRISMA statement. The meta-analysis includes findings from 11 studies evaluating the QoL of PAH patients at baseline and at follow-up (12 weeks) using the Short Form (36) Health Survey (SF-36), the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). RESULTS The mean physical component score (SF-36) for the group was 37.2 points (95% CI: 33.24-41.16) and the heterogeneity coefficient was I²=97.71% (p < 0.001). The mean mental component score (SF-36) was 46.38 (95% CI: 44.21-48.56) and the heterogeneity coefficient was I²=87.92% (p < 0.001). The result indicates improved QoL 12 weeks after the intervention, though three papers did not fully confirm this. The greatest improvement in QoL was found in patients treated with bosentan and iloprost and the smallest improvement in QoL was found in patients treated with epoprostenol sodium. The heterogeneity coefficient was I²=91.36%, p < 0.001 for CAMPHOR and I²=97.65%, p < 0.001 for MLHFQ. CONCLUSIONS PAH patients tend to have a poor QoL, mainly in the physical functioning domain, less so in the psychological functioning domain. QoL may be improved by therapeutic interventions, mainly pharmaceutical ones. Patients with PAH also tend to suffer from depression, anxiety, stress, or sleep disorders. All these factors are significantly correlated with poorer QoL.
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Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis.
Nazarzadeh, M, Bidel, Z, Canoy, D, Copland, E, Wamil, M, Majert, J, Smith Byrne, K, Sundström, J, Teo, K, Davis, BR, et al
Lancet (London, England). 2021;(10313):1803-1810
Abstract
BACKGROUND Blood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials. METHODS We performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons. FINDINGS 145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84-0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76-0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76-0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of β blockers (RR 1·48 [1·27-1·72]) and thiazide diuretics (RR 1·20 [1·07-1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92-1·13]). INTERPRETATION Blood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes. FUNDING British Heart Foundation, National Institute for Health Research, and Oxford Martin School.
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Adverse Cardiovascular Outcomes and Antihypertensive Treatment: A Genome-Wide Interaction Meta-Analysis in the International Consortium for Antihypertensive Pharmacogenomics Studies.
McDonough, CW, Warren, HR, Jack, JR, Motsinger-Reif, AA, Armstrong, ND, Bis, JC, House, JS, Singh, S, El Rouby, NM, Gong, Y, et al
Clinical pharmacology and therapeutics. 2021;(3):723-732
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Abstract
We sought to identify genome-wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome-wide antihypertensive drug-single nucleotide polymorphism (SNP) interaction tests for four drug classes (β-blockers, n = 9,195; calcium channel blockers (CCBs), n = 10,511; thiazide/thiazide-like diuretics, n = 3,516; ACE-inhibitors/ARBs, n = 2,559) and cardiovascular outcomes (incident myocardial infarction, stroke, or death) were analyzed among patients with hypertension of European ancestry. Top SNPs from the meta-analyses were tested for replication of cardiovascular outcomes in an independent Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) study (n = 21,267), blood pressure (BP) response in independent ICAPS studies (n = 1,552), and ethnic validation in African Americans from the Genetics of Hypertension Associated Treatment study (GenHAT; n = 5,115). One signal reached genome-wide significance in the β-blocker-SNP interaction analysis (rs139945292, Interaction P = 1.56 × 10-8 ). rs139945292 was validated through BP response to β-blockers, with the T-allele associated with less BP reduction (systolic BP response P = 6 × 10-4 , Beta = 3.09, diastolic BP response P = 5 × 10-3 , Beta = 1.53). The T-allele was also associated with increased adverse cardiovascular risk within the β-blocker treated patients' subgroup (P = 2.35 × 10-4 , odds ratio = 1.57, 95% confidence interval = 1.23-1.99). The locus showed nominal replication in CHARGE, and consistent directional trends in β-blocker treated African Americans. rs139945292 is an expression quantitative trait locus for the 50 kb upstream gene NTM (neurotrimin). No SNPs attained genome-wide significance for any other drugs classes. Top SNPs were located near CALB1 (CCB), FLJ367777 (ACE-inhibitor), and CES5AP1 (thiazide). The NTM region is associated with increased risk for adverse cardiovascular outcomes and less BP reduction in β-blocker treated patients. Further investigation into this region is warranted.
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Effect of proanthocyanidins on blood pressure: A systematic review and meta-analysis of randomized controlled trials.
Ren, J, An, J, Chen, M, Yang, H, Ma, Y
Pharmacological research. 2021;:105329
Abstract
BACKGROUND Hypertension is a common chronic disease that can lead to serious health problems. Previous studies have not drawn a consistent conclusion about the effect of proanthocyanidins (PCs) on blood pressure (BP). This systematic review and meta-analysis aims to evaluate the effect of PCs supplementation on blood pressure (BP). METHODS A comprehensive literature search was performed in 6 databases (Pubmed, Scopus, ISI Web of Science, the Cochrane Library, Embase and Google Scholar) to identify the randomized controlled trials (RCTs) that evaluated the BP-lowering effect of PCs. Subgroup and sensitivity analyses were conducted to evaluate the potential heterogeneity. Meta-regression analysis was used to evaluate dose effects of PCs on BP. RESULTS A total of 6 studies comprising 376 subjects were included in our meta-analysis to estimate the pooled effect size. This meta-analysis suggested that PCs supplementation could significantly reduce systolic blood pressure (SBP) (WMD: -4.598 mmHg; 95 % CI: -8.037, -1.159; I2 = 33.7 %; p = 0.009), diastolic blood pressure (DBP) (WMD: -2.750 mmHg; 95 % CI: -5.087, -0.412; I2 = 0.0 %; p = 0.021) and mean arterial pressure (MAP) (WMD: -3.366 mmHg; 95 % CI: -6.719, -0.041 mmHg; I2 = 0.0 %; p = 0.049), but had no significant effect on pulse pressure (PP) (WMD: -2.131 mmHg; 95 % CI: -6.292, 2.030; I2 = 0.0 %; p = 0.315). When the studies were stratified according to the duration of the study, there was a significant reduction on SBP in the subset of the trials with <12 weeks of duration. On the contrary, there was a significant reduction on DBP in the subset of the trials with ≥12 weeks of duration. The Subgroup analysis by BMI indicated that a significant reduction on SBP for people with a higher BMI (BMI ≥ 25) and a significant reduction on DBP for people with a lower BMI (BMI < 25). Additional subgroup analysis revealed low-dose-PCs (<245 mg/day) could significantly reduce SBP, DBP and MAP. The meta-regression analyses did not indicate the dose effects of PCs on SBP, DBP, PP and MAP. CONCLUSION Based on the current findings, PCs supplementation may be a useful treatment of hypertensive patients as well as a preventive measure in the prehypertensive and healthy subjects. However, further investigation is needed to confirm these results.
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The Effect of Saffron Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.
Setayesh, L, Ashtary-Larky, D, Clark, CCT, Rezaei Kelishadi, M, Khalili, P, Bagheri, R, Asbaghi, O, Suzuki, K
Nutrients. 2021;(8)
Abstract
BACKGROUND The favorable influences of saffron supplementation on metabolic diseases have previously been shown. We aimed to assess the effects of saffron supplementation on blood pressure in adults. METHODS A systematic search was performed in Scopus, Embase, and the Cochrane library databases to find randomized controlled trials (RCTs) related to the effect of saffron supplementation on blood pressure in adults up to March 2021. The primary search yielded 182 publications, of which eight RCTs were eligible. RESULTS Our results showed that saffron supplementation resulted in a significant decrease in systolic blood pressure (weighted mean difference (WMD): -0.65 mmHg; 95% CI: -1.12 to -0.18, p = 0.006) and diastolic blood pressure (DBP) (WMD: -1.23 mmHg; 95% CI: -1.64 to -0.81, p < 0.001). Moreover, saffron supplementation reduced DBP in a non-linear fashion, based on duration (r = -2.45, p-nonlinearity = 0.008). CONCLUSIONS Saffron supplementation may significantly improve both systolic and diastolic blood pressure in adults. It should be noted that the hypotensive effects of saffron supplementation were small and may not reach clinical importance.
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Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies.
Fogacci, F, Tocci, G, Sahebkar, A, Presta, V, Banach, M, Cicero, AFG
Angiology. 2020;(3):217-225
Abstract
Results of previous clinical trials evaluating the effect of pycnogenol supplementation on blood pressure (BP) are controversial. Therefore, we aimed to assess the impact of pycnogenol on BP through a systematic review of literature and meta-analysis of available randomized, double-blind, placebo-controlled clinical studies (randomized clinical trials [RCTs]). Literature search included SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases up to January 10, 2019 to identify RCTs investigating the impact of pycnogenol on BP. Two investigators independently extracted data on study characteristics, methods, and outcomes. This systematic review and meta-analysis is registered in International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42018112172. Overall, the impact of pycnogenol on BP was reported in 7 trials involving 626 participants. Meta-analysis did not suggest any significant improvement in systolic BP (weighted mean difference [WMD]: -0.028 mm Hg; 95% confidence interval [CI]: -0.182 to 0.127; P = .726; I2 = 46%), diastolic BP (WMD: -0.144 mm Hg; 95% CI: -0.299 to 0.010; P = .067; I2 = 0%), mean arterial pressure (WMD: -0.091 mm Hg; 95% CI: -0.246 to 0.063; P = .246; I2 = 0%), and pulse pressure (WMD: -0.003 mm Hg; 95% CI: -0.151 to 0.158; P = .966; I2 = 0%) following pycnogenol treatment. Results persisted in the leave-one-out sensitivity analysis. Therefore, the present meta-analysis does not suggest any significant effect of pycnogenol on BP.