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European Heart Journal Jul 2023Due to growing environmental focus, plant-based diets are increasing steadily in popularity. Uncovering the effect on well-established risk factors for cardiovascular... (Meta-Analysis)
Meta-Analysis
AIMS
Due to growing environmental focus, plant-based diets are increasing steadily in popularity. Uncovering the effect on well-established risk factors for cardiovascular diseases, the leading cause of death worldwide, is thus highly relevant. Therefore, a systematic review and meta-analysis were conducted to estimate the effect of vegetarian and vegan diets on blood levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B.
METHODS AND RESULTS
Studies published between 1980 and October 2022 were searched for using PubMed, Embase, and references of previous reviews. Included studies were randomized controlled trials that quantified the effect of vegetarian or vegan diets vs. an omnivorous diet on blood lipids and lipoprotein levels in adults over 18 years. Estimates were calculated using a random-effects model. Thirty trials were included in the study. Compared with the omnivorous group, the plant-based diets reduced total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels with mean differences of -0.34 mmol/L (95% confidence interval, -0.44, -0.23; P = 1 × 10-9), -0.30 mmol/L (-0.40, -0.19; P = 4 × 10-8), and -12.92 mg/dL (-22.63, -3.20; P = 0.01), respectively. The effect sizes were similar across age, continent, duration of study, health status, intervention diet, intervention program, and study design. No significant difference was observed for triglyceride levels.
CONCLUSION
Vegetarian and vegan diets were associated with reduced concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B-effects that were consistent across various study and participant characteristics. Plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease.
Topics: Adult; Humans; Diet, Vegan; Diet, Vegetarian; Randomized Controlled Trials as Topic; Lipids; Vegetarians; Cholesterol, LDL; Lipoproteins; Cardiovascular Diseases; Atherosclerosis; Apolipoproteins
PubMed: 37226630
DOI: 10.1093/eurheartj/ehad211 -
Frontiers in Immunology 2022Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages...
Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages are effector cells and accumulate to the damaged and inflamed sites of arteries to internalize native and chemically modified lipoproteins to transform them into cholesterol-loaded foam cells. Foam cell formation is determined by the capacity of phagocytosis, migration, scavenging, and the features of phenotypes. Macrophages are diverse, and the subsets and functions are controlled by their surrounding microenvironment. Generally, macrophages are divided into classically activated (M1) and alternatively activated (M2). Recently, intraplaque macrophage phenotypes are recognized by the stimulation of CXCL4 (M4), oxidized phospholipids (Mox), hemoglobin/haptoglobin complexes [HA-mac/M(Hb)], and heme (Mhem). The pro-atherogenic or anti-atherosclerotic phenotypes of macrophages decide the progression of AS. Besides, apoptosis, necrosis, ferroptosis, autophagy and pyrotopsis determine plaque formation and cardiovascular vulnerability, which may be associated with macrophage polarization phenotypes. In this review, we first summarize the three most popular hypotheses for AS and find the common key factors for further discussion. Secondly, we discuss the factors affecting macrophage polarization and five types of macrophage death in AS progression, especially ferroptosis. A comprehensive understanding of the cellular and molecular mechanisms of plaque formation is conducive to disentangling the candidate targets of macrophage-targeting therapies for clinical intervention at various stages of AS.
Topics: Atherosclerosis; Foam Cells; Humans; Macrophage Activation; Macrophages; Plaque, Atherosclerotic
PubMed: 35432323
DOI: 10.3389/fimmu.2022.843712 -
Circulation Sep 2018With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the association between HIV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HIV.
METHODS
We conducted a systematic review across 5 databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection. A random-effects meta-analysis across 80 studies was used to derive the pooled rate and risk of cardiovascular disease in people living with HIV. We then estimated the temporal changes in the population-attributable fraction and disability-adjusted life-years (DALYs) from HIV-associated cardiovascular disease from 1990 to 2015 at a regional and global level. National cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193 United Nations member states. The main outcome measure was the pooled estimate of the rate and risk of cardiovascular disease in people living with HIV and the national, regional, and global estimates of DALYs from cardiovascular disease associated with HIV.
RESULTS
In 793 635 people living with HIV and a total follow-up of 3.5 million person-years, the crude rate of cardiovascular disease was 61.8 (95% CI, 45.8-83.4) per 10 000 person-years. In comparison with individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95% CI, 1.68-2.77). Over the past 26 years, the global population-attributable fraction from cardiovascular disease attributable to HIV increased from 0.36% (95% CI, 0.21%-0.56%) to 0.92% (95% CI, 0.55%-1.41%), and DALYs increased from 0.74 (95% CI, 0.44-1.16) to 2.57 (95% CI, 1.53-3.92) million. There was marked regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95% CI, 0.43-1.70) and the Asia Pacific (0.39 million, 95% CI, 0.23-0.62) regions. The highest population-attributable fraction and burden were observed in Swaziland, Botswana, and Lesotho.
CONCLUSIONS
People living with HIV are twice as likely to develop cardiovascular disease. The global burden of HIV-associated cardiovascular disease has tripled over the past 2 decades and is now responsible for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa and the Asia Pacific regions.
CLINICAL TRIAL REGISTRATION
URL: https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.
Topics: Adult; Atherosclerosis; Cost of Illness; Female; Global Health; HIV Infections; HIV Long-Term Survivors; Humans; Incidence; Male; Middle Aged; Prevalence; Prognosis; Risk Assessment; Risk Factors; Time Factors
PubMed: 29967196
DOI: 10.1161/CIRCULATIONAHA.117.033369 -
PloS One 2023Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.
OBJECTIVE
The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.
METHODS
Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.
RESULTS
In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01).
CONCLUSION
PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.
Topics: Humans; PCSK9 Inhibitors; Cholesterol, LDL; Myocardial Infarction; Proprotein Convertase 9; Atherosclerosis; Heart Disease Risk Factors; RNA, Small Interfering; Anticholesteremic Agents; Cardiovascular Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38055686
DOI: 10.1371/journal.pone.0295359 -
The Lancet. Global Health Aug 2019Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on peripheral artery disease have emerged, enabling us to provide updated estimates of the prevalence and risk factors for peripheral artery disease globally and regionally and, for the first time, nationally.
METHODS
For this systematic review and analysis, we did a comprehensive literature search for studies reporting on the prevalence of peripheral artery disease in the general population that were published between Jan 1, 2011, and April 30, 2019, in PubMed, MEDLINE, Embase, the Global Health database, CINAHL, the Global Health Library, the Allied and Complementary Medicine Database, and ProQuest Dissertations and Theses Global. We also included the Global Peripheral Artery Disease Study of 2013 and the China Peripheral Artery Disease Study as sources. Peripheral artery disease had to be defined as an ankle-brachial index lower than or equal to 0·90. With a purpose-built data collection form, data on study characteristics, sample characteristics, prevalence, and risk factors were abstracted from all the included studies identified from the sources. Age-specific and sex-specific prevalence of peripheral artery disease was estimated in both high-income countries (HICs) and low-income and middle-income countries (LMICs). We also did random-effects meta-analyses to pool the odds ratios of 30 risk factors for peripheral artery disease in HICs and LMICs. UN population data were used to generate the number of people affected by the disease in 2015. Finally, we derived the regional and national numbers of people with peripheral artery disease on the basis of a risk factor-based model.
FINDINGS
We included 118 articles for systematic review and analysis. The prevalence of peripheral artery disease increased consistently with age. At younger ages, prevalence was slightly higher in LMICs than HICs (4·32%, 95% CI 3·01-6·29, vs 3·54%, 1·17-10·24, at 40-44 years), but the increase with age was greater in HICs than LMICs, leading to a higher prevalence in HICs than LMICs at older ages (21·24%, 15·22-28·90, vs 12·04%, 8·67-16·60, at 80-84 years). In HICs, prevalence was slightly higher in women than in men up to age 75 years (eg, 7·81%, 3·97-14·77, vs 6·60%, 3·74-11·38, at 55-59 years), whereas in LMICs little difference was found between women and men (eg, 6·40%, 5·06-8·05, vs 6·37%, 4·74-8·49, at 55-59 years). Overall, the global prevalence of peripheral artery disease in people aged 25 years and older was 5·56%, 3·79-8·55, and the prevalence estimate was higher in HICs than that in LMICs (7·37%, 4·35-13·66, vs 5·09%, 3·64-7·24). Smoking, diabetes, hypertension, and hypercholesterolaemia were major risk factors for peripheral artery disease. Globally, a total of 236·62 million people aged 25 years and older were living with peripheral artery disease in 2015, among whom 72·91% were in LMICs. The Western Pacific Region had the most peripheral artery disease cases (74·08 million), whereas the Eastern Mediterranean Region had the least (14·67 million). More than two thirds of the global peripheral artery disease cases were concentrated in 15 individual countries in 2015.
INTERPRETATION
Peripheral artery disease continues to become an increasingly serious public health problem, especially in LMICs. With the demographic trend towards ageing and projected rise in important risk factors, a larger burden of peripheral artery disease is to be expected in the foreseeable future.
FUNDING
None.
Topics: Adult; Aged; Aged, 80 and over; Female; Global Health; Humans; Male; Middle Aged; Peripheral Arterial Disease; Prevalence; Risk Factors
PubMed: 31303293
DOI: 10.1016/S2214-109X(19)30255-4 -
PloS One 2020The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i's) and lower extremity amputation is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i's) and lower extremity amputation is unclear.
PURPOSE
To systematically review randomized control trials (RCTs) and observational studies quantifying risk of lower extremity amputations associated with SGLT2i use.
DATA SOURCES AND STUDY SELECTION
We searched PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from January 2011 to February 2020 for RCTs and observational studies including lower extremity amputation outcomes for individuals with type 2 diabetes mellitus treated with SGLT2i's vs. alternative treatments or placebo.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data.
MAIN OUTCOMES AND MEASURES
Our primary outcome was risk of lower limb amputation. Secondary outcomes included peripheral arterial disease, peripheral vascular disease, venous ulcerations, and diabetic foot infections. We also evaluated the risk of bias. We conducted random and fixed effects relative risk meta-analysis of RCTs.
RESULTS
After screening 2,006 studies, 12 RCTs and 18 observational studies were included, of which 7 RCTs and 18 observational studies had at least one event. The random effects meta-analysis of 7 RCTs suggested the absence of a statistically significant association between SGLT2i exposure with evidence of substantial statistical heterogeneity (n = 424/23,716 vs n = 267/18,737 in controls; RR 1.28, CI's 0.93-1.76; I2 = 62.0%; p = 0.12) whereas fixed effects analysis showed an increased risk with statistical heterogeneity (RR 1.27, 1.09-1.48; I2 = 62%; p = 0.003). Subgroup analysis of canagliflozin vs placebo showed a statistically significantly increased risk in a fixed effects meta-analysis (n = 2 RCTs, RR 1.59, 1.26-2.01; I2 = 88%; p = 0.0001) whereas the meta-analysis of dapagliflozin or empagliflozin (n = 2 RCTs each) and a single RCT for ertugliflozin did not show a significantly increased risk. The findings from observational studies were too heterogeneous to be pooled in a meta-analysis and draw meaningful conclusions. Both randomized and observational studies were of generally good methodological quality.
CONCLUSIONS
Overall, there was no consistent evidence of SGLT2i exposure and increased risk of amputation. The increased risk of amputation seen in the large, long-term Canagliflozin Cardiovascular Assessment Study (CANVAS) trial for canagliflozin, and select observational studies, merits continued exploration.
Topics: Amputation, Surgical; Benzhydryl Compounds; Glucosides; Humans; Lower Extremity; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Risk; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds
PubMed: 32502190
DOI: 10.1371/journal.pone.0234065 -
The Cochrane Database of Systematic... Jun 2023Amputation is described as the removal of an external part of the body by trauma, medical illness or surgery. Amputations caused by vascular diseases (dysvascular... (Review)
Review
BACKGROUND
Amputation is described as the removal of an external part of the body by trauma, medical illness or surgery. Amputations caused by vascular diseases (dysvascular amputations) are increasingly frequent, commonly due to peripheral arterial disease (PAD), associated with an ageing population, and increased incidence of diabetes and atherosclerotic disease. Interventions for motor rehabilitation might work as a precursor to enhance the rehabilitation process and prosthetic use. Effective rehabilitation can improve mobility, allow people to take up activities again with minimum functional loss and may enhance the quality of life (QoL). Strength training is a commonly used technique for motor rehabilitation following transtibial (below-knee) amputation, aiming to increase muscular strength. Other interventions such as motor imaging (MI), virtual environments (VEs) and proprioceptive neuromuscular facilitation (PNF) may improve the rehabilitation process and, if these interventions can be performed at home, the overall expense of the rehabilitation process may decrease. Due to the increased prevalence, economic impact and long-term rehabilitation process in people with dysvascular amputations, a review investigating the effectiveness of motor rehabilitation interventions in people with dysvascular transtibial amputations is warranted.
OBJECTIVES
To evaluate the benefits and harms of interventions for motor rehabilitation in people with transtibial (below-knee) amputations resulting from peripheral arterial disease or diabetes (dysvascular causes).
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 9 January 2023.
SELECTION CRITERIA
We included randomised controlled trials (RCT) in people with transtibial amputations resulting from PAD or diabetes (dysvascular causes) comparing interventions for motor rehabilitation such as strength training (including gait training), MI, VEs and PNF against each other.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. prosthesis use, and 2.
ADVERSE EVENTS
Our secondary outcomes were 3. mortality, 4. QoL, 5. mobility assessment and 6. phantom limb pain. We use GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included two RCTs with a combined total of 30 participants. One study evaluated MI combined with physical practice of walking versus physical practice of walking alone. One study compared two different gait training protocols. The two studies recruited people who already used prosthesis; therefore, we could not assess prosthesis use. The studies did not report mortality, QoL or phantom limb pain. There was a lack of blinding of participants and imprecision as a result of the small number of participants, which downgraded the certainty of the evidence. We identified no studies that compared VE or PNF with usual care or with each other. MI combined with physical practice of walking versus physical practice of walking (one RCT, eight participants) showed very low-certainty evidence of no difference in mobility assessment assessed using walking speed, step length, asymmetry of step length, asymmetry of the mean amount of support on the prosthetic side and on the non-amputee side and Timed Up-and-Go test. The study did not assess adverse events. One study compared two different gait training protocols (one RCT, 22 participants). The study used change scores to evaluate if the different gait training strategies led to a difference in improvement between baseline (day three) and post-intervention (day 10). There were no clear differences using velocity, Berg Balance Scale (BBS) or Amputee Mobility Predictor with PROsthesis (AMPPRO) in training approaches in functional outcome (very low-certainty evidence). There was very low-certainty evidence of little or no difference in adverse events comparing the two different gait training protocols.
AUTHORS' CONCLUSIONS
Overall, there is a paucity of research in the field of motor rehabilitation in dysvascular amputation. We identified very low-certainty evidence that gait training protocols showed little or no difference between the groups in mobility assessments and adverse events. MI combined with physical practice of walking versus physical practice of walking alone showed no clear difference in mobility assessment (very low-certainty evidence). The included studies did not report mortality, QoL, and phantom limb pain, and evaluated participants already using prosthesis, precluding the evaluation of prosthesis use. Due to the very low-certainty evidence available based on only two small trials, it remains unclear whether these interventions have an effect on the prosthesis use, adverse events, mobility assessment, mortality, QoL and phantom limb pain. Further well-designed studies that address interventions for motor rehabilitation in dysvascular transtibial amputation may be important to clarify this uncertainty.
Topics: Humans; Phantom Limb; Amputation, Surgical; Walking; Peripheral Arterial Disease; Diabetes Mellitus
PubMed: 37276273
DOI: 10.1002/14651858.CD013711.pub2 -
Journal of Foot and Ankle Research 2019The ankle brachial index (ABI) is widely used in clinical practice as a non-invasive method to detect the presence and severity of peripheral arterial disease (PAD)....
BACKGROUND
The ankle brachial index (ABI) is widely used in clinical practice as a non-invasive method to detect the presence and severity of peripheral arterial disease (PAD). Current guidelines suggest that it should be used to monitor potential progression of PAD in affected individuals. As such, it is important that the test is reliable when used for repeated measurements, by the same or different health practitioners. This systematic review aims to examine the literature to evaluate the inter- and intra-rater reliability of the ABI.
METHODS
A systematic search of MEDLINE, EMBASE and CINAHL Complete was conducted to 20 January 2019. Two authors independently reviewed and selected relevant studies and extracted the data. Methodological quality was determined using the Quality Appraisal of Reliability (QAREL) Checklist.
RESULTS
Fifteen studies of ABI reliability in a range of patient populations were identified as suitable for inclusion in the review: seven considered inter-rater reliability, four intra-rater reliability, and four studies evaluated both inter- and intra-rater reliability. Inter-rater reliability was found to be highly variable, with intraclass correlation coefficients (ICC's) ranging from poor to excellent (ICC 0.42-1.00), while intra-rater also demonstrated considerable variation, with ICCs from 0.42-0.98. Meta-analysis was not possible due to the lack of statistical information reported.
CONCLUSIONS
Results of included studies suggest the inter- and intra-tester reliability of the ABI is acceptable. However, inconsistencies in obtaining systolic pressure measurements, calculating ABI values, and incomplete reporting of methodologies and statistical analysis make it difficult to determine the validity of the results of included studies. Further research, with more consistent reliability methodology, statistical analysis and reporting conducted in populations at risk of PAD is needed to conclusively determine the ABI reliability.
Topics: Adult; Aged; Ankle Brachial Index; Female; Humans; Male; Middle Aged; Peripheral Arterial Disease; Reproducibility of Results
PubMed: 31388357
DOI: 10.1186/s13047-019-0350-1 -
Nutrients Sep 2020Matrix gla protein (MGP) is an important vitamin K-dependent inhibitor of vascular calcification. High levels of uncarboxylated, dephosphorylated MGP have been...
Matrix gla protein (MGP) is an important vitamin K-dependent inhibitor of vascular calcification. High levels of uncarboxylated, dephosphorylated MGP have been associated with vascular calcification and are responsive to vitamin K treatment. In this systematic review, we summarize the available evidence examining whether vitamin K supplementation improves surrogate measures of cardiovascular disease including artery and valve calcification, atherosclerosis and artery stiffening. Data from controlled trials of adults were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Web of Science Core Collection. We identified nine randomized controlled trials for review, including trials of vitamin K or vitamin K supplementation, that assessed a surrogate measure of cardiovascular disease including arterial calcification, atherosclerosis or arterial stiffening. For each trial, the risk of bias was assessed applying Cochrane Collaboration methodology. The findings indicate that vitamin K does not consistently prevent progression of calcification, atherosclerosis or arterial stiffness. There may be some benefit in people with calcification at study entry. Studies were heterogenous, with relatively short follow-up and outcome measures were varied. While vitamin K supplementation clearly improves the carboxylation of dephosphoylated MGP, its role in mitigating vascular calcification is uncertain, based on current evidence.
Topics: Animals; Arteries; Atherosclerosis; Calcium-Binding Proteins; Cardiovascular Diseases; Databases, Factual; Dietary Supplements; Disease Progression; Extracellular Matrix Proteins; Humans; Randomized Controlled Trials as Topic; Vascular Calcification; Vascular Stiffness; Vitamin K; Vitamin K 2; Matrix Gla Protein
PubMed: 32977548
DOI: 10.3390/nu12102909 -
Drugs Aug 2022High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD.
METHODS
A systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group.
RESULTS
Twenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking.
CONCLUSION
Clopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.
Topics: Aspirin; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Ticagrelor; Vitamin K
PubMed: 35997941
DOI: 10.1007/s40265-022-01756-6