-
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 -
Food & Function Oct 2023: Previous studies have shown the potential role of vitamin K supplementation in the prevention and treatment of many diseases. However, the effect of vitamin K... (Meta-Analysis)
Meta-Analysis
: Previous studies have shown the potential role of vitamin K supplementation in the prevention and treatment of many diseases. However, the effect of vitamin K supplementation on blood glucose remains controversial. The purpose of this study was to assess the effects of vitamin K supplementation on glycemia-related indicators, including Fasting Blood Sugar (FBS), Fasting Insulin (FINS) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The potential association between vitamin K and type 2 diabetes mellitus (T2DM) risk was also evaluated. : Up to April 2023, Cochrane, PubMed, Web of Science, Medline and EMBASE databases were searched to assess the effects of vitamin K on blood glucose and the risk of developing T2DM. : A -analysis of seven studies (813 participants) found vitamin K supplementation significantly reduced FBS (SMD = -0.150 mg dl, 95% CI = -0.290, -0.010 mg dl) and HOMA-IR (SMD = -0.200, 95% CI = -0.330, -0.060), but not FINS. Five studies with a total of 105 798 participants were included in the -analysis of the association between vitamin K and T2DM. The results showed that vitamin K was associated with the reduced risk of developing T2DM (HR = 0.79, 95% CI [0.71-0.88], < 0.001). : The -analysis demonstrated that vitamin K supplementation had a significant effect on the regulation of FBS and HOMA-IR in the population. Moreover, vitamin K was associated with the reduced risk of developing T2DM. Considering some limitations found in this study, additional data from large clinical trials are needed.
Topics: Humans; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Insulin; Insulin Resistance; Vitamin K
PubMed: 37724446
DOI: 10.1039/d3fo02943c -
Circulation. Cardiovascular Quality and... Mar 2020Stroke reduction with direct oral anticoagulants (DOACs) in atrial fibrillation (AF) is dependent on adherence and persistence in the real-world setting. Individual... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke reduction with direct oral anticoagulants (DOACs) in atrial fibrillation (AF) is dependent on adherence and persistence in the real-world setting. Individual study estimates of DOAC adherence/persistence rates have been discordant. Our aims were to characterize real-world observational evidence for DOAC adherence/persistence and evaluate associated clinical outcomes in patients with AF.
METHODS AND RESULTS
PubMed, EMBASE, and CINAHL were searched from inception to June 2018. Observational studies that reported real-world DOAC adherence/persistence in patients with AF were included. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Outcomes included DOAC mean proportion of days covered or medication possession ratio, proportion of good adherence (proportion of days covered/medication possession ratio ≥80%), persistence, DOAC versus vitamin K antagonists persistence, and clinical outcomes associated with nonadherence/nonpersistence. Forty-eight observational studies with 594 784 unique patients with AF (59% male; mean age 71 years) were included. The overall pooled mean proportion of days covered/medication possession ratio was 77% (95% CI, 75%-80%), proportion of patients with good adherence was 66% (95% CI, 63%-70%), and proportion persistent was 69% (95% CI, 65%-72%). The pooled proportion of patients with good adherence was 71% (95% CI, 64%-78%) for apixaban, 60% (95% CI, 52%-68%) for dabigatran, and 70% (95% CI, 64%-75%) for rivaroxaban. Similar patterns were found for pooled persistence by agent. The pooled persistence was higher with DOACs than vitamin K antagonists (odds ratio, 1.44 [95% CI, 1.12-.86]). DOAC nonadherence was associated with an increased risk of stroke (hazard ratio, 1.39 [95% CI, 1.06-1.81]).
CONCLUSIONS
Suboptimal adherence and persistence to DOACs was common in patients with AF, with 1 in 3 patients adhering to their DOAC <80% of the time, which was associated with poor clinical outcomes in nonadherent patients. Although it is convenient that DOACs do not require laboratory monitoring, greater effort in monitoring for and interventions to prevent nonadherence may be necessary to optimize stroke prevention. Increased clinician awareness of DOAC nonadherence may help identify at-risk patients.
Topics: Administration, Oral; Aged; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Male; Medication Adherence; Middle Aged; Observational Studies as Topic; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome
PubMed: 32148102
DOI: 10.1161/CIRCOUTCOMES.119.005969 -
Frontiers in Cardiovascular Medicine 2021Antiphospholipid antibody syndrome (APS) requires long-term anticoagulation to prevent recurrent thrombosis. Direct oral anticoagulants (DOACs) have been increasingly... (Review)
Review
Antiphospholipid antibody syndrome (APS) requires long-term anticoagulation to prevent recurrent thrombosis. Direct oral anticoagulants (DOACs) have been increasingly used in APS patients, but contradictory guidelines recommendations on their use do exist. We performed a systematic review of literature including studies investigating the role of DOACs in APS patients. At this aim, PubMed and Cochrane databases were searched according to PRISMA guidelines. We identified 14 studies which investigated the use of DOACs in patients with APS, of which 3 randomized clinical trials (RCTs), 1 analysis of 3 RCTs, 7 case series and 3 cohort studies (2 prospective and 1 retrospective). Among DOACs, rivaroxaban was the most used ( = 531), followed by dabigatran ( = 90) and apixaban ( = 46). Regarding guidelines indications, the 2019 European Society of Cardiology (ESC) and American Society of Hematology (ASH) guidelines recommend against the use of DOACs in all APS patients. The European League Against Rheumatism (EULAR), British Society for Haematology (BSH), and International Society on Thrombosis and Haemostasis (ISTH) guidance provided more detailed indications stating that warfarin should be the first-choice treatment but DOACs may be considered in patients (1) already on a stable anticoagulation with a DOAC, (2) with low-quality anticoagulation by warfarin, (3) unwilling/unable to undergo INR monitoring, (4) with contraindications or serious adverse events under warfarin. Patients with arterial APS or triple positivity should be treated with warfarin while venous APS with single or double positivity may be candidate to DOACs, but high-quality studies are needed.
PubMed: 34414220
DOI: 10.3389/fcvm.2021.715878 -
The Lancet. Oncology Oct 2019Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during...
Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.
Topics: Anticoagulants; Central Venous Catheters; Factor Xa Inhibitors; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Vena Cava Filters; Venous Thromboembolism; Vitamin K
PubMed: 31492632
DOI: 10.1016/S1470-2045(19)30336-5 -
Thrombosis and Haemostasis Jan 2022The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical... (Meta-Analysis)
Meta-Analysis
The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical guidance for cardiologists, neurologists, geriatricians, and general practitioners in the Asia-Pacific region. In these years, many important new data regarding stroke prevention in AF were reported. The practice guidelines subcommittee members comprehensively reviewed updated information on stroke prevention in AF, and summarized them in this 2021 focused update of the 2017 consensus guidelines of the APHRS on stroke prevention in AF. We highlighted and focused on several issues, including the importance of the AF Better Care pathway, the advantages of non-vitamin K antagonist oral anticoagulants (NOACs) for Asians, the considerations of use of NOACs for Asian AF patients with single one stroke risk factor beyond gender, the role of lifestyle factors on stroke risk, the use of oral anticoagulants during the "coronavirus disease 2019" pandemic, etc. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician's decision remains the most important factor in the management of AF.
Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Asia; Atrial Fibrillation; COVID-19; Catheter Ablation; Female; Heart Disease Risk Factors; Hemorrhage; Holistic Health; Humans; Male; Pandemics; Percutaneous Coronary Intervention; Risk Assessment; SARS-CoV-2; Societies, Medical; Stroke
PubMed: 34773920
DOI: 10.1055/s-0041-1739411 -
Scandinavian Journal of Surgery : SJS :... Jun 2021Acute mesenteric venous thrombosis accounts for up to 20% of all patients with acute mesenteric ischemia in high-income countries. Acute mesenteric venous thrombosis is...
BACKGROUND AND AIMS
Acute mesenteric venous thrombosis accounts for up to 20% of all patients with acute mesenteric ischemia in high-income countries. Acute mesenteric venous thrombosis is nowadays relatively more often diagnosed with intravenous contrast-enhanced computed tomography in the portal phase than at explorative laparotomy No high-quality comparative studies between anticoagulation alone, endovascular therapy, or surgery exists. The aim of the present systematic review was to offer a contemporary overview on management.
MATERIALS AND METHODS
Eleven relevant published original studies with series of at least ten patients were retrieved from a Pub Med search between 2015 and 2020 using the Medical Subject Heading term "mesenteric venous thrombosis."
RESULTS
When MVT is diagnosed early, immediate anticoagulation with either unfractionated heparin or subcutaneous low-molecular-weight heparin should commence. Surgeons need to be aware of the importance to scrutinize the computed tomography images themselves for assessment of secondary intestinal abnormalities to mesenteric venous thrombosis and the risk of bowel resection and worse prognosis. Progression toward peritonitis is an indication for explorative laparotomy and assessment of bowel viability. Frank transmural small bowel necrosis should be resected and bowel anastomosis may be delayed for several days until second look. Meanwhile, intravenous full-dose unfractionated heparin should be given at the end of the first operation. Postoperative major intra-abdominal or gastrointestinal bleeding occurs rarely, but the heparin effect can instantaneously be reversed by . Patients who do not improve during conservative therapy with anticoagulation alone but without developing peritonitis may be subjected to endovascular therapy in expert centers. When the patient's intestinal function has recovered, with or without bowel resection, switch from parenteral unfractionated heparin or low-molecular-weight heparin therapy to oral anticoagulation can be performed. There is a trend that direct oral anticoagulants are increasingly used instead of vitamin K antagonists. Up to now, direct oral anticoagulants have been shown to be equally effective with the same rate of bleeding complications. Patients with no strong permanent trigger factor for mesenteric venous thrombosis such as intra-abdominal cancer should undergo blood screening for inherited and acquired thrombophilia.
CONCLUSION
Early diagnosis with emergency computed tomography with intravenous contrast-enhancement and imaging in the portal phase and anticoagulation therapy is necessary to be able to have a succesful non-operative succesful course.
Topics: Anticoagulants; Heparin; Humans; Mesenteric Ischemia; Mesenteric Veins; Venous Thrombosis
PubMed: 33118463
DOI: 10.1177/1457496920969084 -
Journal of the American Society of... May 2022Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in...
BACKGROUND
Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in CKD remain uncertain.
METHODS
We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compared with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3-5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiologic methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.
RESULTS
There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E-coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal.
CONCLUSIONS
Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.
Topics: Female; Humans; Magnesium; Male; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification
PubMed: 35232774
DOI: 10.1681/ASN.2021101327 -
Frontiers in Nutrition 2023Vascular calcification (VC) is a complex process that has been linked to conditions including cardiovascular diseases and chronic kidney disease. There is an ongoing...
BACKGROUND
Vascular calcification (VC) is a complex process that has been linked to conditions including cardiovascular diseases and chronic kidney disease. There is an ongoing debate about whether vitamin K (VK) can effectively prevent VC. To assess the efficiency and safety of VK supplementation in the therapies of VC, we performed a systematic review and meta-analysis of recent studies.
METHODS
We searched major databases, including PubMed, the Cochrane Library, Embase databases, and Web of Science up until August 2022. 14 randomized controlled trials (RCTs) describing the outcomes of treatment for VK supplementation with VC have been included out of 332 studies. The results were reported in the change of coronary artery calcification (CAC) scores, other artery and valve calcification, vascular stiffness, and dephospho-uncarboxylated matrix Gla protein (dp-ucMGP). The reports of severe adverse events were recorded and analyzed.
RESULTS
We reviewed 14 RCTs, comprising a total of 1,533 patients. Our analysis revealed that VK supplementation has a significant effect on CAC scores, slowing down the progression of CAC [ = 34%, MD= -17.37, 95% CI (-34.18, -0.56), = 0.04]. The study found that VK supplementation had a significant impact on dp-ucMGP levels, as compared to the control group, where those receiving VK supplementation had lower values [ = 71%, MD = -243.31, 95% CI (-366.08, -120.53), = 0.0001]. Additionally, there was no significant difference in the adverse events between the groups [ = 31%, RR = 0.92, 95% CI (-0.79,1.07), = 0.29].
CONCLUSION
VK may have therapeutic potential for alleviating VC, especially CAC. However, more rigorously designed RCTs are required to verify the benefits and efficacy of VK therapy in VC.
PubMed: 37252246
DOI: 10.3389/fnut.2023.1115069 -
Clinical Kidney Journal Dec 2023Vitamin K supplementation has been considered recently as a potential treatment for addressing vascular calcification in chronic kidney disease patients. We conducted a...
Vitamin K supplementation has been considered recently as a potential treatment for addressing vascular calcification in chronic kidney disease patients. We conducted a systematic review and meta-analysis to summarize the impact of vitamin K supplementation in dialysis patients. Electronic databases were searched for clinical randomized trials among patients treated with vitamin K. Random effects models were performed and risk of bias was evaluated with Cochrane tools and the search was conducted until 15 of September 2023. Eleven trials comprising 830 patients (both adult and pediatric, mainly hemodialysis) compared vitamin K with different controls: lower doses of vitamin K, standard care or placebo. Vitamin K supplementation had no effect on mortality. Vitamin K administration improved vitamin K levels and led to lower levels of dp-uc-MGP and moderately increased calcium levels [0.18 (0.04-0.32)]. Vitamin K1 proved more potency in reducing dp-uc-MGP [SMD -1.64 (-2.05, -1.23) vs. -0.56 (-0.82, -0.31)] and also raised serum vitamin K levels in comparison with vitamin K2 [5.69 (3.43, 7.94) vs. 2.25 (-2.36, 6.87)]. While it did not have a proved benefit in changing calcification scores [-0.14 (-0.37 ± 0.09)], vitamin K proved to be a safe product. There was some concern with bias. Vitamin K supplementation has no impact on mortality and did not show significant benefit in reversing calcification scores. Vitamin K1 improved vitamin K deposits and lowered dp-uc-MGP, which is a calcification biomarker more than vitamin K2. As it proved to be a safe product, additional randomized well-powered studies with improved treatment regimens are needed to establish the true impact of vitamin K in dialysis patients.
PubMed: 38046003
DOI: 10.1093/ckj/sfad255