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Intensive Care Medicine Jun 2020Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings... (Meta-Analysis)
Meta-Analysis Review
Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings in ECMO patients and the underlying mechanisms are only partially elucidated. The purpose of this meta-analysis and systematic review was to thoroughly summarize and discuss the existing knowledge of platelet profile in adult ECMO population. All studies meeting the inclusion criteria (detailed data about platelet count and function) were selected, after screening literature from July 1975 to August 2019. Twenty-one studies from 1.742 abstracts were selected. The pooled prevalence of thrombocytopenia in ECMO patients was 21% (95% CI 12.9-29.0; 14 studies). Thrombocytopenia prevalence was 25.4% (95% CI 10.6-61.4; 4 studies) in veno-venous ECMO, whereas it was 23.2% (95% CI 11.8-34.5; 6 studies) in veno-arterial ECMO. Heparin-induced thrombocytopenia prevalence was 3.7% (95% CI 1.8-5.5; 12 studies). Meta-regression revealed no significant association between ECMO duration and thrombocytopenia. Platelet function impairment was described in 7 studies. Impaired aggregation was shown in 5 studies, whereas loss of platelet receptors was found in one trial, and platelet activation was described in 2 studies. Platelet transfusions were needed in up to 50% of the patients. Red blood cell transfusions were administered from 46 to 100% of the ECMO patients. Bleeding events varied from 16.6 to 50.7%, although the cause and type of haemorrhage was not consistently reported. Thrombocytopenia and platelet dysfunction are common in ECMO patients, regardless the type of ECMO mode. The underlying mechanisms are multifactorial, and understanding and management are still limited. Further research to design appropriate strategies and protocols for its monitoring, management, or prevention should be matter of thorough investigations.
Topics: Adult; Blood Platelets; Extracorporeal Membrane Oxygenation; Hemorrhage; Humans; Platelet Count; Thrombocytopenia
PubMed: 32328725
DOI: 10.1007/s00134-020-06031-4 -
European Journal of Vascular and... Nov 2022The role of antithrombotic therapy in the management of aortic and peripheral aneurysms is unclear. This systematic review and meta-analysis aimed to assess the impact... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The role of antithrombotic therapy in the management of aortic and peripheral aneurysms is unclear. This systematic review and meta-analysis aimed to assess the impact of antithrombotics on clinical outcomes for aortic and peripheral aneurysms.
METHODS
Medline, Embase, and CENTRAL databases were searched. Randomised controlled trials and observational studies investigating the effect of antithrombotic therapy on clinical outcomes for patients with any aortic or peripheral artery aneurysm were included.
RESULTS
Fifty-nine studies (28 with antiplatelet agents, 12 anticoagulants, two intra-operative heparin, and 16 any antithrombotic agent) involving 122 102 patients were included. Abdominal aortic aneurysm (AAA) growth rate was not significantly associated with the use of antiplatelet therapy (SMD -0.36 mm/year; 95% CI -0.75 - 0.02; p = .060; GRADE certainty: very low). Antithrombotics were associated with increased 30 day mortality for patients with AAAs undergoing intervention (OR 2.30; 95% CI 1.51 - 3.51; p < .001; GRADE certainty: low). Following intervention, antiplatelet therapy was associated with reduced long term all cause mortality (HR 0.84; 95% CI 0.76 - 0.92; p < .001; GRADE certainty: moderate), whilst anticoagulants were associated with increased all cause mortality (HR 1.64; 95% CI 1.14 - 2.37; p = .008; GRADE certainty: very low), endoleak within three years (OR 1.99; 95% CI 1.10 - 3.60; p = .020; I = 60%; GRADE certainty: very low), and an increased re-intervention rate at one year (OR 3.25; 95% CI 1.82 - 5.82; p < .001; I = 35%; GRADE certainty: moderate). Five studies examined antithrombotic therapy for popliteal aneurysms. Meta-analysis was not possible due to heterogeneity.
CONCLUSIONS
There was a lack of high quality data examining antithrombotic therapy for patients with aneurysms. Antiplatelet therapy was associated with a reduction in post-intervention all cause mortality for AAA, whilst anticoagulants were associated with an increased risk of all cause mortality, endoleak, and re-intervention. Large, well designed trials are still required to determine the therapeutic benefits of antithrombotic agents in this setting.
Topics: Humans; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Endoleak; Aortic Aneurysm, Abdominal; Anticoagulants
PubMed: 35853579
DOI: 10.1016/j.ejvs.2022.07.008 -
The Cochrane Database of Systematic... Feb 2022Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet agents may be different in people with chronic kidney... (Review)
Review
BACKGROUND
Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet agents may be different in people with chronic kidney disease (CKD) for whom occlusive atherosclerotic events are less prevalent, and bleeding hazards might be increased. This is an update of a review first published in 2013.
OBJECTIVES
To evaluate the benefits and harms of antiplatelet agents in people with any form of CKD, including those with CKD not receiving renal replacement therapy, patients receiving any form of dialysis, and kidney transplant recipients.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 13 July 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We selected randomised controlled trials of any antiplatelet agents versus placebo or no treatment, or direct head-to-head antiplatelet agent studies in people with CKD. Studies were included if they enrolled participants with CKD, or included people in broader at-risk populations in which data for subgroups with CKD could be disaggregated.
DATA COLLECTION AND ANALYSIS
Four authors independently extracted data from primary study reports and any available supplementary information for study population, interventions, outcomes, and risks of bias. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from numbers of events and numbers of participants at risk which were extracted from each included study. The reported RRs were extracted where crude event rates were not provided. Data were pooled using the random-effects model. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We included 113 studies, enrolling 51,959 participants; 90 studies (40,597 CKD participants) compared an antiplatelet agent with placebo or no treatment, and 29 studies (11,805 CKD participants) directly compared one antiplatelet agent with another. Fifty-six new studies were added to this 2021 update. Seven studies originally excluded from the 2013 review were included, although they had a follow-up lower than two months. Random sequence generation and allocation concealment were at low risk of bias in 16 and 22 studies, respectively. Sixty-four studies reported low-risk methods for blinding of participants and investigators; outcome assessment was blinded in 41 studies. Forty-one studies were at low risk of attrition bias, 50 studies were at low risk of selective reporting bias, and 57 studies were at low risk of other potential sources of bias. Compared to placebo or no treatment, antiplatelet agents probably reduces myocardial infarction (18 studies, 15,289 participants: RR 0.88, 95% CI 0.79 to 0.99, I² = 0%; moderate certainty). Antiplatelet agents has uncertain effects on fatal or nonfatal stroke (12 studies, 10.382 participants: RR 1.01, 95% CI 0.64 to 1.59, I² = 37%; very low certainty) and may have little or no effect on death from any cause (35 studies, 18,241 participants: RR 0.94, 95 % CI 0.84 to 1.06, I² = 14%; low certainty). Antiplatelet therapy probably increases major bleeding in people with CKD and those treated with haemodialysis (HD) (29 studies, 16,194 participants: RR 1.35, 95% CI 1.10 to 1.65, I² = 12%; moderate certainty). In addition, antiplatelet therapy may increase minor bleeding in people with CKD and those treated with HD (21 studies, 13,218 participants: RR 1.55, 95% CI 1.27 to 1.90, I² = 58%; low certainty). Antiplatelet treatment may reduce early dialysis vascular access thrombosis (8 studies, 1525 participants) RR 0.52, 95% CI 0.38 to 0.70; low certainty). Antiplatelet agents may reduce doubling of serum creatinine in CKD (3 studies, 217 participants: RR 0.39, 95% CI 0.17 to 0.86, I² = 8%; low certainty). The treatment effects of antiplatelet agents on stroke, cardiovascular death, kidney failure, kidney transplant graft loss, transplant rejection, creatinine clearance, proteinuria, dialysis access failure, loss of primary unassisted patency, failure to attain suitability for dialysis, need of intervention and cardiovascular hospitalisation were uncertain. Limited data were available for direct head-to-head comparisons of antiplatelet drugs, including prasugrel, ticagrelor, different doses of clopidogrel, abciximab, defibrotide, sarpogrelate and beraprost.
AUTHORS' CONCLUSIONS
Antiplatelet agents probably reduced myocardial infarction and increased major bleeding, but do not appear to reduce all-cause and cardiovascular death among people with CKD and those treated with dialysis. The treatment effects of antiplatelet agents compared with each other are uncertain.
Topics: Humans; Platelet Aggregation Inhibitors; Proteinuria; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 35224730
DOI: 10.1002/14651858.CD008834.pub4 -
The Cochrane Database of Systematic... Oct 2020Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is associated with high morbidity and mortality. Pentoxifylline, one of many drugs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is associated with high morbidity and mortality. Pentoxifylline, one of many drugs used to treat IC, acts by decreasing blood viscosity, improving erythrocyte flexibility, and promoting microcirculatory flow and tissue oxygen concentration. Many studies have evaluated the efficacy of pentoxifylline in treating people with PAD, but results of these studies are variable. This is the second update of a review first published in 2012.
OBJECTIVES
To determine the efficacy of pentoxifylline in improving the walking capacity (i.e. pain-free walking distance and total (absolute, maximum) walking distance) of people with stable intermittent claudication, Fontaine stage II.
SEARCH METHODS
For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 28 January 2020. There were no language restrictions.
SELECTION CRITERIA
We included all double-blind, randomised controlled trials (RCTs) comparing pentoxifylline versus placebo or any other pharmacological intervention in people with IC Fontaine stage II.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, assessed the included studies, matched data and resolved disagreements by discussion. Review authors assessed the methodological quality of studies using the Cochrane 'Risk of bias' tool and collected results related to the outcomes of interest, pain-free walking distance (PFWD), total walking distance (TWD), ankle-brachial pressure index (ABI), quality of life (QoL) and side effects. Comparison of studies was based on duration and dose of pentoxifylline. We used GRADE criteria to assess the certainty of the evidence.
MAIN RESULTS
We identified no new eligible studies for this update. This review includes 24 studies with 3377 participants. Seventeen studies compared pentoxifylline versus placebo. The seven remaining studies compared pentoxifylline with flunarizine (one study), aspirin (one study), Gingko biloba extract (one study), nylidrin hydrochloride (one study), prostaglandin E1 (two studies), and buflomedil and nifedipine (one study). Risk of bias for the individual studies was generally unclear because there was a lack of methodological reporting for many of the included studies, especially regarding randomisation and allocation methods. Most included studies did not provide adequate information to allow selective reporting to be judged and did not report blinding of assessors. Heterogeneity between included studies was considerable with regards to multiple variables, including duration of treatment, dose of pentoxifylline, baseline walking distance and participant characteristics; therefore, pooled analysis for comparisons which included more than one study, was not possible. Pentoxifylline compared to placebo Of 17 studies comparing pentoxifylline with placebo, 11 reported PFWD and 14 reported TWD; the difference in percentage improvement in PFWD for pentoxifylline over placebo ranged from -33.8% to 73.9% and in TWD ranged from 1.2% to 155.9%. It was not possible to pool the data of the studies because data were insufficient and findings from individual trials were unclear. Most included studies suggested a possible improvement in PFWD and TWD for pentoxifylline over placebo (both low-certainty evidence). The five studies which evaluated pre-exercise ABI comparing pentoxifylline and placebo found no evidence of a difference (moderate-certainty evidence). Two of the three studies that evaluated QoL between people who received pentoxifylline and placebo were larger studies that used validated QoL tools and generally found no evidence of a difference between groups. One small, short-term study, which did not specify which QoL tool was used, reported improved QoL in the pentoxifylline group (moderate-certainty evidence). Pentoxifylline generally was well tolerated; the most commonly reported side effects consisted of gastrointestinal symptoms such as nausea (low-certainty evidence). Certainty of the evidence from this review was low or moderate, with downgrading due to risk of bias concerns, inconsistencies between studies and the inability to evaluate imprecision because meta-analysis could not be undertaken. The seven remaining studies compared pentoxifylline with either flunarizine, aspirin, Gingko biloba extract, nylidrin hydrochloride, prostaglandin E1, or buflomedil and nifedipine; data were too limited to allow any meaningful conclusions to be made.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence for the effects of pentoxifylline compared to placebo, or other treatments, for IC. There is low-certainty evidence that pentoxifylline may improve PFWD and TWD compared to placebo, but no evidence of a benefit to ABI or QoL (moderate-certainty evidence). Pentoxifylline was reported to be generally well tolerated (low-certainty evidence). Given the large degree of heterogeneity between the studies, the role of pentoxifylline for people with IC Fontaine class II remains uncertain.
Topics: Ankle Brachial Index; Humans; Intermittent Claudication; Pentoxifylline; Platelet Aggregation Inhibitors; Quality of Life; Randomized Controlled Trials as Topic; Vasodilator Agents; Walking
PubMed: 33063850
DOI: 10.1002/14651858.CD005262.pub4 -
Acta Neurochirurgica Jan 2023Discontinuation of aspirin (ASA) prior to elective craniotomies is common practice. However, patients treated with ASA for secondary prevention bear a higher risk for... (Review)
Review
BACKGROUND/AIM
Discontinuation of aspirin (ASA) prior to elective craniotomies is common practice. However, patients treated with ASA for secondary prevention bear a higher risk for thromboembolic complications. Aim of this systematic review is to investigate the risks and benefits of perioperative continuation and discontinuation of ASA in elective craniotomies.
METHODS
PubMed and Embase databases were searched. Inclusion criteria were retro- and prospective studies, reporting hemorrhagic and thromboembolic complications in patients in whom ASA was either continued or discontinued perioperatively in elective craniotomies. We excluded shunt operations and emergency cases. The MINORS (Methodological index for non-randomized studies) score was used to quantify the methodological quality of the eligible studies.
RESULTS
Out of 523 publications, 7 met the eligibility criteria (cumulative cohort of 646 patients). The mean MINORS score for the comparative studies was 18.7/24 (± SD 2.07, range: 17-22) and 9/16 for the unique non-comparative study, indicating an overall weak methodological quality of the included studies. 57.1% of the patients underwent craniotomy for intra- and extra-axial tumor removal, 39.0% for bypass surgery and 3.9% for neurovascular lesions (other than bypass). In 31.0% of the cases, ASA was prescribed for primary and in 69.0% for secondary prevention. ASA was continued perioperatively in 61.8% and discontinued in 38.2% of the cases. The hemorrhagic complication rate was 3% (95% CI [0.01-0.05]) in the ASA continuation group (Con-Group) and 3% (95% CI [0.01-0.09]) in the discontinuation group (Disc-Group) (p = 0.9). The rate of thromboembolic events in the Con-Group was 3% (95% CI [0.01-0.06]) in comparison to 6% (95% CI [0.02-0.14]) in the Disc-Group (p = 0.1).
CONCLUSION
Perioperative continuation of ASA in elective craniotomies does not seem to be associated with an increased hemorrhagic risk. The potential beneficial effect of ASA continuation on thromboembolic events needs to be further investigated in patients under ASA for secondary prevention.
Topics: Humans; Aspirin; Platelet Aggregation Inhibitors; Prospective Studies; Hemorrhage; Thromboembolism; Craniotomy; Risk Assessment
PubMed: 36376767
DOI: 10.1007/s00701-022-05416-2 -
Orthopaedic Journal of Sports Medicine Apr 2022Platelet-rich plasma (PRP) exerts its effect through the release of growth factors and cytokines from the platelet concentrate. Certain medications may affect platelet... (Review)
Review
A Systematic Review on the Effect of Common Medications on Platelet Count and Function: Which Medications Should Be Stopped Before Getting a Platelet-Rich Plasma Injection?
BACKGROUND
Platelet-rich plasma (PRP) exerts its effect through the release of growth factors and cytokines from the platelet concentrate. Certain medications may affect platelet count or function, resulting in decreased efficacy of PRP injections.
PURPOSE
To systematically review the literature regarding common medications and their effects on platelets to establish guidelines for which medications should be stopped before obtaining a PRP injection.
STUDY DESIGN
Systematic review; Level of evidence, 2.
METHODS
This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search for studies assessing the effect of common medications on platelet count or platelet function was performed of the PubMed, Cochrane Library, Web of Science, and OpenGrey databases. Inclusion criteria were as follows: drug studied was aspirin, acetaminophen, a nonsteroidal anti-inflammatory drug (NSAID), a statin, or gabapentin; human participants; and article in the English language. Risk of bias was assessed using the Cochrane Risk of Bias tool and the Risk of Bias in Non-randomised Studies-of Interventions tool.
RESULTS
A total of 1711 studies were identified through the initial search, with 20 studies meeting all inclusion criteria. No studies involving gabapentin met all inclusion criteria. Patients treated with aspirin (268 patients) or acetaminophen (13 patients) showed a significant decrease in platelet aggregation. Statin therapy (73 patients) did not result in a significant decrease in platelet aggregation. Patients who took NSAIDs (172 patients) demonstrated significantly decreased platelet aggregation only when treated with nonselective formulations. Those treated with cyclooxygenase (COX)-2-selective NSAIDs showed no significant difference in platelet aggregation. Treatment with aspirin, acetaminophen, statins, or NSAIDs did not lead to a significant decrease in platelet count.
CONCLUSION
Aspirin, acetaminophen, and nonselective NSAIDs should be considered for suspension before a PRP injection because of their potential to diminish the effects of the injection. COX-2-selective NSAIDs and statins do not need to be withheld before a PRP injection.
PubMed: 35434168
DOI: 10.1177/23259671221088820 -
The Cochrane Database of Systematic... Jun 2021Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication (exercise-induced lower limb pain relieved by rest). These patients have a three- to six-fold increase in cardiovascular mortality. Cilostazol is a drug licensed for the use of improving claudication distance and, if shown to reduce cardiovascular risk, could offer additional clinical benefits. This is an update of the review first published in 2007.
OBJECTIVES
To determine the effect of cilostazol on initial and absolute claudication distances, mortality and vascular events in patients with stable intermittent claudication.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 9 November 2020.
SELECTION CRITERIA
We considered double-blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other drugs used to improve claudication distance in patients with stable intermittent claudication.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We assessed the risk of bias with the Cochrane risk of bias tool. Certainty of the evidence was evaluated using GRADE. For dichotomous outcomes, we used odds ratios (ORs) with corresponding 95% confidence intervals (CIs) and for continuous outcomes we used mean differences (MDs) and 95% CIs. We pooled data using a fixed-effect model, or a random-effects model when heterogeneity was identified. Primary outcomes were initial claudication distance (ICD) and quality of life (QoL). Secondary outcomes were absolute claudication distance (ACD), revascularisation, amputation, adverse events and cardiovascular events.
MAIN RESULTS
We included 16 double-blind, RCTs (3972 participants) comparing cilostazol with placebo, of which five studies also compared cilostazol with pentoxifylline. Treatment duration ranged from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Cilostazol dose ranged from 100 mg to 300 mg; pentoxifylline dose ranged from 800 mg to 1200 mg. The certainty of the evidence was downgraded by one level for all studies because publication bias was strongly suspected. Other reasons for downgrading were imprecision, inconsistency and selective reporting. Cilostazol versus placebo Participants taking cilostazol had a higher ICD compared with those taking placebo (MD 26.49 metres; 95% CI 18.93 to 34.05; 1722 participants; six studies; low-certainty evidence). We reported QoL measures descriptively due to insufficient statistical detail within the studies to combine the results; there was a possible indication in improvement of QoL in the cilostazol treatment groups (low-certainty evidence). Participants taking cilostazol had a higher ACD compared with those taking placebo (39.57 metres; 95% CI 21.80 to 57.33; 2360 participants; eight studies; very-low certainty evidence). The most commonly reported adverse events were headache, diarrhoea, abnormal stools, dizziness, pain and palpitations. Participants taking cilostazol had an increased odds of experiencing headache compared to participants taking placebo (OR 2.83; 95% CI 2.26 to 3.55; 2584 participants; eight studies; moderate-certainty evidence).Very few studies reported on other outcomes so conclusions on revascularisation, amputation, or cardiovascular events could not be made. Cilostazol versus pentoxifylline There was no difference detected between cilostazol and pentoxifylline for improving walking distance, both in terms of ICD (MD 20.0 metres, 95% CI -2.57 to 42.57; 417 participants; one study; low-certainty evidence); and ACD (MD 13.4 metres, 95% CI -43.50 to 70.36; 866 participants; two studies; very low-certainty evidence). One study reported on QoL; the study authors reported no difference in QoL between the treatment groups (very low-certainty evidence). No study reported on revascularisation, amputation or cardiovascular events. Cilostazol participants had an increased odds of experiencing headache compared with participants taking pentoxifylline at 24 weeks (OR 2.20, 95% CI 1.16 to 4.17; 982 participants; two studies; low-certainty evidence).
AUTHORS' CONCLUSIONS
Cilostazol has been shown to improve walking distance in people with intermittent claudication. However, participants taking cilostazol had higher odds of experiencing headache. There is insufficient evidence about the effectiveness of cilostazol for serious events such as amputation, revascularisation, and cardiovascular events. Despite the importance of QoL to patients, meta-analysis could not be undertaken because of differences in measures used and reporting. Very limited data indicated no difference between cilostazol and pentoxifylline for improving walking distance and data were too limited for any conclusions on other outcomes.
Topics: Aged; Bias; Cilostazol; Humans; Intermittent Claudication; Middle Aged; Myocardial Infarction; Pentoxifylline; Peripheral Vascular Diseases; Placebos; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Tetrazoles; Walking
PubMed: 34192807
DOI: 10.1002/14651858.CD003748.pub5 -
The Cochrane Database of Systematic... Dec 2020Frostbite is a thermal injury caused when tissue is exposed to sub-zero temperatures (in degrees Celsius) long enough for ice crystals to form in the affected tissue....
BACKGROUND
Frostbite is a thermal injury caused when tissue is exposed to sub-zero temperatures (in degrees Celsius) long enough for ice crystals to form in the affected tissue. Depending on the degree of tissue damage, thrombosis, ischaemia, necrosis (tissue death), gangrene and ultimately amputation may occur. Several interventions for frostbite injuries have been proposed, such as hyperbaric oxygen therapy, sympathectomy (nerve block), thrombolytic (blood-thinning) therapy and vasodilating agents such as iloprost, reserpine, pentoxifylline and buflomedil, but the benefits and harms of these interventions are unclear.
OBJECTIVES
To assess the benefits and harms of the different management options for frostbite injuries.
SEARCH METHODS
On 25 February 2020, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S), as well as trials registers. Shortly before publication, we searched Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, OpenGrey and GreyLit (9 November 2020) again. We investigated references from relevant articles, and corresponded with a trial author.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any medical intervention, e.g. pharmacological therapy, topical treatments or rewarming techniques, for frostbite injuries to another treatment, placebo or no treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data. We used Review Manager 5 for statistical analysis of dichotomous data with risk ratio (RR) with 95% confidence intervals (CIs). We used the Cochrane 'Risk of bias' tool to assess bias in the included trial. We assessed incidence of amputations, rates of serious and non-serious adverse events, acute pain, chronic pain, ability to perform activities of daily living, quality of life, withdrawal rate from medical therapy due to adverse events, occupational effects and mortality. We used GRADE to assess the quality of the evidence.
MAIN RESULTS
We included one, open-label randomised trial involving 47 participants with severe frostbite injuries. We judged this trial to be at high risk of bias for performance bias, and uncertain risk for attrition bias; all other risk of bias domains we judged as low. All participants underwent rapid rewarming, received 250 mg of aspirin and 400 mg intravascular (IV) buflomedil (since withdrawn from practice), and were then randomised to one of three treatment groups for the following eight days. Group 1 received additional IV buflomedil 400 mg for one hour per day. Group 2 received the prostacyclin, iloprost, 0.5 ng to 2 ng/kg/min IV for six hours per day. Group 3 received IV iloprost 2 ng/kg/min for six hours per day plus fibrinolysis with 100 mg recombinant tissue plasminogen activator (rtPA) for the first day only. The results suggest that iloprost and iloprost plus rtPA may reduce the rate of amputations in people with severe frostbite compared to buflomedil alone, RR 0.05 (95% CI 0.00 to 0.78; P = 0.03; very low-quality evidence) and RR 0.31 (95% CI 0.10 to 0.94; P = 0.04; very low-quality evidence), respectively. Iloprost may be as effective as iloprost plus rtPA at reducing the amputation rate, RR 0.14 (95% CI 0.01 to 2.56; P = 0.19; very low-quality evidence). There were no reported deaths or withdrawals due to adverse events in any of the groups; we assessed evidence for both outcomes as being of very low quality. Adverse events (including flushing, nausea, palpitations and vomiting) were common, but not reported separately by comparator arm (very low-quality evidence). The included study did not measure the outcomes of acute pain, chronic pain, ability to perform activities of daily living, quality of life or occupational effects.
AUTHORS' CONCLUSIONS
There is a paucity of evidence regarding interventions for frostbite injuries. Very low-quality evidence from a single small trial indicates that iloprost, and iloprost plus rtPA, in combination with buflomedil may reduce the need for amputation in people with severe frostbite compared to buflomedil alone. However, buflomedil has been withdrawn from use. High quality randomised trials are needed to establish firm evidence for the treatment of frostbite injuries.
Topics: Amputation, Surgical; Aspirin; Bias; Drug Therapy, Combination; Epoprostenol; Fibrinolytic Agents; Frostbite; Humans; Iloprost; Platelet Aggregation Inhibitors; Pyrrolidines; Recombinant Proteins; Rewarming; Tissue Plasminogen Activator; Vasodilator Agents
PubMed: 33341943
DOI: 10.1002/14651858.CD012980.pub2 -
JACC. Cardiovascular Interventions Dec 2021This meta-analysis and systematic review was performed to evaluate the clinical relevance of subclinical leaflet thrombosis (SLT) following transcatheter aortic valve... (Meta-Analysis)
Meta-Analysis Review
This meta-analysis and systematic review was performed to evaluate the clinical relevance of subclinical leaflet thrombosis (SLT) following transcatheter aortic valve replacement. PubMed, Web of Science, and CENTRAL were searched for eligible randomized and nonrandomized studies until November 2020. Risk ratios (RRs) or odds ratios and 95% CIs were calculated, using a random-effects model. Overall, 25 studies were eligible for the analysis and comprised a total of 11,098 patients. The median incidence of SLT was 6% at a median follow-up of 30 days. Use of intra-annular valves was associated with 2-fold greater risk for the development of SLT compared with use of supra-annular valves. There was no difference in the risk for SLT (RR: 0.97; 95% CI: 0.72-1.29; P = 0.83) between single-antiplatelet therapy (SAPT) and dual-antiplatelet therapy (DAPT), whereas oral anticoagulation (OAC) was associated with a 58% relative risk reduction for SLT (RR: 0.42; 95% CI: 0.29-0.61; P < 0.00001) compared with SAPT and DAPT. In patients with diagnosed leaflet thrombosis at follow-up, the risk for stroke or transient ischemic attack was increased by 2.6-fold (RR: 2.56; 95% CI: 1.60-4.09; P < 0.00001) compared with patients without leaflet thrombosis. In patients diagnosed with SLT, the odds of SLT resolution increased by 99% after switch from antiplatelet agents to OAC (odds ratio: 0.01; 95% CI: 0.00-0.06; P < 0.00001). To summarize, indication-based use of OAC after transcatheter aortic valve replacement is associated with a lower risk for SLT compared with SAPT and DAPT. Switching to OAC seems to be effective for SLT resolution. As SLT increased the odds of stroke or transient ischemic attack in the included population, further studies are needed to investigate whether screening tests for SLT and appropriate antithrombotic therapy improve long-term valve functionality and clinical prognosis.
Topics: Aortic Valve; Aortic Valve Stenosis; Dual Anti-Platelet Therapy; Humans; Platelet Aggregation Inhibitors; Risk Factors; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 34949391
DOI: 10.1016/j.jcin.2021.09.019 -
Frontiers in Cardiovascular Medicine 2023Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and... (Review)
Review
BACKGROUD
Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS.
METHODS
We used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality.
RESULTS
Five trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low.
CONCLUSIONS
These results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.
PubMed: 37089879
DOI: 10.3389/fcvm.2023.1040936