-
International Journal of Cardiology Oct 2022Several patients undergoing transcatheter aortic valve replacement (TAVR) also require oral anticoagulation (OAC) for atrial fibrillation (AF) or deep vein... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several patients undergoing transcatheter aortic valve replacement (TAVR) also require oral anticoagulation (OAC) for atrial fibrillation (AF) or deep vein thromboembolism. However, the optimal type of OAC strategy (direct oral anticoagulants, DOACs, or vitamin K antagonists, VKA) is still unclear in this setting.
METHOD
We performed systematic literature research and meta-analysis in PubMed, Medline, and EMBASE databases for studies reporting either all-cause mortality, major/life-threatening bleeding or stroke events.
RESULTS
Ten observational studies and two randomized controlled trials (RCTs) including a total of 29,485 patients were eligible for inclusion. Compared to VKA, DOACs use after TAVR was associated with a modest but significantly lower rates of all-cause mortality (RR 0.90; 95% CI: 0.81-0.99, p-value 0.04) with results mainly driven by observational studies. Cardiovascular mortality (RR 1.03; 95% CI: 0.81-1.30; p-value 0.84), total stroke events (RR 0.97; 95% CI: 0.76-1.23, p-value 0.79), major/life-threatening bleeding (RR 0.93; 95% CI: 0.72-1.21, p-value 0.61) and minor bleeding (RR 0.96; 95% CI: 0.74-1.23; p-value 0.72) were similar between VKA and DOACs.
CONCLUSION
Considering the totality of available evidence, in patients who underwent TAVR with a concomitant indication for OAC, DOACs-based strategy is an effective and safe anticoagulation strategy compared to VKA.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K
PubMed: 35901908
DOI: 10.1016/j.ijcard.2022.07.039 -
Hormone and Metabolic Research =... Mar 2018Type 2 diabetes mellitus (T2DM) is one of the most important public health issues. Vitamin K supplementation might have favorable effect on risk factors of T2DM. The aim... (Meta-Analysis)
Meta-Analysis Review
Type 2 diabetes mellitus (T2DM) is one of the most important public health issues. Vitamin K supplementation might have favorable effect on risk factors of T2DM. The aim of this study was to perform a systematic review and meta-analysis of interventional studies to examine the effect of vitamin K supplementation on glycemic indices. A systematic search was performed in electronic databases including PubMed, Science Direct, ProQuest, Institute of Scientific Information Web of Science, and Google scholar up to July 2017. We used a random effects model to estimate pooled effect size of fasting blood sugar (FBS), 2-h oral glucose tolerance test (2-h OGTT), fasting insulin (FINS), and homeostasis model assessment-estimated insulin resistance (HOMA-IR). Five clinical trials (533 participants) fulfilled the eligibility criteria of the present meta-analysis. Overall, meta-analysis could not show any beneficial effect of vitamin K supplementation on FBS (-0.91 mg/dl, 95% CI: -2.57, 0.76, p=0.28), FINS (-0.35 μIU/ml, 95% CI: -1.70, 1.00, p=0.61), HOMA-IR (-0.06, 95% CI: -0.32, -0.19, p=0.63), and 2-h OGTT (-4.00 mg/dl, 95% CI: -20.00, 11.99, p=0.62). Sensitivity analysis showed that overall estimates were not affected by elimination of any study. We did not observe any evidence regarding publication bias. In conclusion, vitamin K supplementation had no significant effect on glycemic control in healthy subjects. However, further studies should be performed on diabetic and pre-diabetic patients to determine the effect of vitamin K supplementation on impaired glycemic control.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Prediabetic State; Vitamin K
PubMed: 29523009
DOI: 10.1055/s-0044-100616 -
Stroke Jan 2018The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation.
METHODS
We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs.
RESULTS
From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents (<0.00001 for all comparisons).
CONCLUSIONS
Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban.
Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Female; Humans; Intracranial Hemorrhages; Male; Polymers; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Saliva, Artificial; Stroke; Vitamin K; Warfarin
PubMed: 29167388
DOI: 10.1161/STROKEAHA.117.018395 -
Journal of Nutritional Science 2024Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is necessary because of the increased mortality risk of that. The aim of our meta-analysis is to reveal the general effect of vitamin K supplementation on its related risk factors. Original databases were searched using standard keywords to identify all randomized clinical trials (RCTs) investigating the effects of vitamin K on CVD. Pooled weighted mean difference (WMD) and 95 % confidence intervals (95 % CI) were achieved by random-model effect analysis for the best estimation of outcomes. The statistical heterogeneity was determined using the Cochran's test and statistics. Seventeen studies were included in this systematic review and meta-analysis. The pooled findings showed that vitamin K supplementation can reduce homeostatic model assessment insulin resistance (HOMA-IR) (WMD: -0⋅24, 95 % CI: -0⋅49, -0⋅02, = 0⋅047) significantly compared to the placebo group. However, no significant effect was observed on other outcomes. Subgroup analysis showed a significant effect of vitamin K2 supplementation compared to vitamin K1 supplementation on HOMA-IR. However, no significant effect was observed on other variables. Also, subgroup analysis showed no potential effect of vitamin K supplementation on any outcome and omitting any articles did not affect the final results. We demonstrated that supplementation with vitamin K has no effect on anthropometrics indexes, CRP, glucose metabolism, and lipid profile factors except HOMA-IR.
Topics: Humans; Dietary Supplements; Vitamin K; Blood Glucose; Insulin Resistance; Cardiovascular Diseases
PubMed: 38282652
DOI: 10.1017/jns.2023.106 -
ESC Heart Failure Oct 2022Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a... (Meta-Analysis)
Meta-Analysis
AIMS
Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT.
METHODS AND RESULTS
We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta-analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between-group difference in all-cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow-up (RR = 1.06, P = 0.13) was observed.
CONCLUSIONS
Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.
Topics: Humans; Vitamin K; Anticoagulants; Thrombosis; Hemorrhage; Stroke; Embolism
PubMed: 35894752
DOI: 10.1002/ehf2.14084 -
Health Technology Assessment... Sep 2009To determine the clinical and cost-effectiveness of vitamin K in preventing osteoporotic fractures in postmenopausal women. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the clinical and cost-effectiveness of vitamin K in preventing osteoporotic fractures in postmenopausal women.
DATA SOURCES
Searches were conducted in May 2007 in MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, BIOSIS, CINAHL, DARE, NHS EED and HTA databases, AMED, NRR, Science Citation Index and Current Controlled Trials. The MEDLINE search was updated in March 2009.
REVIEW METHODS
Selected studies were assessed and subjected to data extraction and quality assessment using standard methods. Where appropriate, meta-analysis was carried out. A mathematical model was constructed to estimate the cost-effectiveness of vitamin K1.
RESULTS
The electronic literature searches identified 1078 potentially relevant articles. Of these, 14 articles relating to five trials that compared vitamin K with a relevant comparator in postmenopausal women with osteoporosis or osteopenia met the review inclusion criteria. The double-blind ECKO trial compared 5 mg of phylloquinone (vitamin K1) with placebo in Canadian women with osteopenia but without osteoporosis. Four open-label trials used 45 mg of menatetrenone (vitamin K2) in Japanese women with osteoporosis; the comparators were no treatment, etidronate or calcium. The methodological quality of the ECKO trial was good; however, all four menatetrenone trials were poorly reported and three were very small (n < 100 in each group). Phylloquinone was associated with a statistically significant reduction in the risk of clinical fractures relative to placebo [relative risk 0.46, 95% confidence interval (CI) 0.22 to 0.99]; morphometric vertebral fractures were not reported. The smaller menatetrenone trials found that menatetrenone was associated with a reduced risk of morphometric vertebral fractures relative to no treatment or calcium; however, the larger Osteoporosis Fracture (OF) study found no evidence of a reduction in vertebral fracture risk. The three smaller trials found no significant difference between treatment groups in non-vertebral fracture incidence. In the ECKO trial, phylloquinone was not associated with an increase in adverse events. In the menatetrenone trials, adverse event reporting was generally poor; however, in the OF study, menatetrenone was associated with a significantly higher incidence of skin and skin appendage lesions. No published economic evaluations of vitamin K were found and a mathematical model was thus constructed to estimate the cost-effectiveness of vitamin K1. Comparators were alendronate, risedronate and strontium ranelate. Vitamin K1 and alendronate were markedly more cost-effective than either risedronate or strontium ranelate. The base-case results favoured vitamin K1, but this relied on many assumptions, particularly on the efficacy of preventing hip and vertebral fractures. Calculation of the expected value of sampled information was conducted assuming a randomised controlled trial of 5 years' duration comparing alendronate with vitamin K1. The costs incurred in obtaining updated efficacy data from a trial with 2000 women per arm were estimated to be a cost-effective use of resources.
CONCLUSIONS
There is currently large uncertainty over whether vitamin K1 is more cost-effective than alendronate; further research is required. It is unlikely that the present prescribing policy (i.e. alendronate as first-line treatment) would be altered.
Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Cost-Benefit Analysis; Female; Fractures, Bone; Humans; Models, Econometric; Osteoporosis, Postmenopausal; Quality-Adjusted Life Years; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamins
PubMed: 19818211
DOI: 10.3310/hta13450 -
The Cochrane Database of Systematic... Sep 2023Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent... (Review)
Review
BACKGROUND
Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review.
OBJECTIVES
To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers, most recently on 29 November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation to placebo or no intervention, in people with AMD.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by Cochrane.
MAIN RESULTS
We included 26 studies conducted in the USA, Europe, China, and Australia. These studies enroled 11,952 people aged 65 to 75 years and included slightly more women (on average 56% women). We judged the studies that contributed data to the review to be at low or unclear risk of bias. Thirteen studies compared multivitamins with control in people with early and intermediate AMD. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 3 studies, 2445 participants; moderate-certainty evidence). In people with early AMD, who are at low risk of progression, this means there would be approximately four fewer cases of progression to late AMD for every 1000 people taking vitamins (one fewer to six fewer cases). In people with intermediate AMD at higher risk of progression, this corresponds to approximately 78 fewer cases of progression for every 1000 people taking vitamins (26 fewer to 126 fewer). AREDS also provided evidence of a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence), and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (measured with the Visual Function Questionnaire) in treated compared with non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). In exploratory subgroup analyses in the follow-on study to AREDS (AREDS2), replacing beta-carotene with lutein/zeaxanthin gave hazard ratios (HR) of 0.82 (95% CI 0.69 to 0.96), 0.78 (95% CI 0.64 to 0.94), 0.94 (95% CI 0.70 to 1.26), and 0.88 (95% CI 0.75 to 1.03) for progression to late AMD, neovascular AMD, geographic atrophy, and vision loss, respectively. Six studies compared lutein (with or without zeaxanthin) with placebo and one study compared a multivitamin including lutein/zeaxanthin with multivitamin alone. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA; almost all participants in AREDS2 also took the original AREDS supplementation formula. People taking lutein/zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05) compared with control (1 study, 4176 participants, 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein/zeaxanthin and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (Visual Function Questionnaire) was similar between groups (MD 1.21, 95% CI -2.59 to 5.01; 2 studies, 308 participants; moderate-certainty evidence). One study in Australia randomised 1204 people to vitamin E or placebo with four years of follow-up; 19% of participants had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05; very low-certainty evidence). There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47; low-certainty evidence). There were no data on neovascular AMD, geographic atrophy, or quality of life. Five studies compared zinc with placebo. Evidence largely drawn from the largest study (AREDS) found a lower progression to late AMD over six years (OR 0.83, 95% CI 0.70 to 0.98; 3 studies, 3790 participants; moderate-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 2 studies, 3791 participants; moderate-certainty evidence). There were no data on quality of life. Gastrointestinal symptoms were the main reported adverse effect. In AREDS, zinc was associated with a higher risk of genitourinary problems in men, but no difference was seen between high- and low-dose zinc groups in AREDS2. Most studies were too small to detect rare adverse effects. Data from larger studies (AREDS/AREDS2) suggested there may be little or no effect on mortality with multivitamin (HR 0.87, 95% CI 0.60 to 1.25; low-certainty evidence) or lutein/zeaxanthin supplementation (HR 1.06, 95% CI 0.87 to 1.31; very low-certainty evidence), but confirmed the increased risk of lung cancer with beta-carotene, mostly in former smokers.
AUTHORS' CONCLUSIONS
Moderate-certainty evidence suggests that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows down progression to late AMD. People with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, exploratory subgroup analyses from one large American study support the view that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula.
Topics: Male; Female; Humans; Antioxidants; Vitamins; Geographic Atrophy; beta Carotene; Lutein; Zeaxanthins; Minerals; Dietary Supplements; Macular Degeneration; Vitamin A; Vitamin K; Zinc; Malnutrition
PubMed: 37702300
DOI: 10.1002/14651858.CD000254.pub5 -
Journal of Personalized Medicine Sep 2022Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high... (Review)
Review
Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high response variability hamper their management. Several patients experience fluctuations in dose−response and are at increased risk of over- or under-anticoagulation. Therefore, it is essential to monitor the prothrombin time/international normalized ratio to determine the so-called stable dose and to adjust the dosage accordingly. Three polymorphisms, CYP2C9∗2, CYP2C9∗3 and VKORC1-1639G>A, are associated with increased sensitivity to VKAs. Other polymorphisms are associated with a request for a higher dose and VKA resistance. We described the clinical cases of two patients who were referred to the Clinical Pharmacology and Pharmacogenetics Unit of the University Hospital of Salerno for pharmacological counseling. One of them showed hypersensitivity and the other one was resistant to VKAs. A systematic review was performed to identify randomized clinical trials investigating the impact of pharmacogenetic testing on increased sensitivity and resistance to VKAs. Although international guidelines are available and information on the genotype-guided dosing approach has been included in VKA drug labels, VKA pharmacogenetic testing is not commonly required. The clinical cases and the results of the systematically reviewed RCTs demonstrate that the pharmacogenetic-based VKA dosing model represents a valuable resource for reducing VKA-associated adverse events.
PubMed: 36294717
DOI: 10.3390/jpm12101578 -
Archives of Internal Medicine Jun 2006Observational and some experimental data suggest that low intake of vitamin K may be associated with an increased risk of fracture. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Observational and some experimental data suggest that low intake of vitamin K may be associated with an increased risk of fracture.
OBJECTIVE
To assess whether oral vitamin K (phytonadione and menaquinone) supplementation can reduce bone loss and prevent fractures.
DATA SOURCES
The search included the following electronic databases: MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), the Cochrane Library (issue 2, 2005), the ISI Web of Science (1945 to June 2005), the National Research Register (inception to the present), Current Controlled Trials, and the Medical Research Council Research Register.
STUDY SELECTION
Randomized controlled trials that gave adult participants oral phytonadione and menaquinone supplements for longer than 6 months were included in this review.
DATA EXTRACTION
Four authors extracted data on changes in bone density and type of fracture. All articles were double screened and double data extracted.
DATA SYNTHESIS
Thirteen trials were identified with data on bone loss, and 7 reported fracture data. All studies but 1 showed an advantage of phytonadione and menaquinone in reducing bone loss. All 7 trials that reported fracture effects were Japanese and used menaquinone. Pooling the 7 trials with fracture data in a meta-analysis, we found an odds ratio (OR) favoring menaquinone of 0.40 (95% confidence interval [CI], 0.25-0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip fractures, and an OR of 0.19 (95% CI, 0.11-0.35) for all nonvertebral fractures.
CONCLUSIONS
This systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss. In the case of the latter, there is a strong effect on incident fractures among Japanese patients.
Topics: Bone Density; Fractures, Bone; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin K 1; Vitamin K 2; Vitamins
PubMed: 16801507
DOI: 10.1001/archinte.166.12.1256 -
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