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Journal of the National Cancer Institute Nov 2021Loss of ovarian function is a recognized adverse effect of chemotherapy for breast cancer and of great importance to patients. Little is known about the ovarian toxicity...
BACKGROUND
Loss of ovarian function is a recognized adverse effect of chemotherapy for breast cancer and of great importance to patients. Little is known about the ovarian toxicity of newer cancer treatments. This study examined whether breast cancer clinical trials include assessment of the impact of trial interventions on ovarian function.
METHODS
Eligible trials were phase III (neo)adjuvant trials of pharmacologic treatments for breast cancer, recruiting between June 2008 and October 2019, which included premenopausal women. MEDLINE, EMBASE, Clinicaltrials.gov, and EudraCT were searched. Data were extracted from trial publications, protocols, databases, and a survey sent to all trial chairs. Tests of statistical significance were 2-sided.
RESULTS
Of 2354 records identified, 141 trials were eligible. Investigational treatments included chemotherapy (36.9%), HER2 targeted (24.8%), endocrine (12.8%), immunotherapy (7.8%), cyclin-dependent kinase 4/6 inhibitors (5.0%), and poly-ADP-ribose polymerase inhibitors (2.8%). Ovarian function was a prespecified endpoint in 13 (9.2%) trials. Forty-five (31.9%) trials collected ovarian function data, but only 33 (23.4%) collected posttrial-intervention data. Common postintervention data collected included menstruation (15.6%), pregnancy (13.5%), estradiol (9.9%), and follicle-stimulating hormone levels (8.5%). Only 4 (2.8%) trials collected postintervention anti-müllerian hormone levels, and 3 (2.1%) trials collected antral follicle count. Of 22 trials investigating immunotherapy, cyclin-dependent kinase 4/6 inhibitors, or poly-ADP-ribose polymerase inhibitors, none specified ovarian function as an endpoint, but 4 (18.2%) collected postintervention ovarian function data.
CONCLUSIONS
The impact of pharmacologic interventions on ovarian function is infrequently assessed in phase III breast cancer (neo)adjuvant trials that include premenopausal women. Trialists should consider inclusion of ovarian function endpoints when designing clinical trials, given its importance for informed decision making.
Topics: Female; Humans; Pregnancy; Adenosine Diphosphate Ribose; Breast Neoplasms; Cyclin-Dependent Kinase 4; Ovary; Premenopause; Clinical Trials, Phase III as Topic
PubMed: 34048575
DOI: 10.1093/jnci/djab111 -
Archives of Gynecology and Obstetrics Aug 2021To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy... (Meta-Analysis)
Meta-Analysis Review
Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis.
PURPOSE
To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer.
RESULTS
We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29-0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67-1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events).
CONCLUSIONS
PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.
Topics: Adenosine Diphosphate; Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Ribose; Treatment Outcome
PubMed: 34021367
DOI: 10.1007/s00404-021-06070-2 -
Medicine Apr 2021In this analysis, we aimed to compare the efficacy and safety of dual therapy (DT) with a non-vitamin K oral anticoagulant (NOAC) and an adenosine diphosphate receptor... (Comparative Study)
Comparative Study Meta-Analysis
Dual therapy with an oral non-vitamin K antagonist and a P2Y12 inhibitor vs triple therapy with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus patients with co-existing atrial fibrillation following percutaneous coronary intervention: A meta-analysis.
BACKGROUND
In this analysis, we aimed to compare the efficacy and safety of dual therapy (DT) with a non-vitamin K oral anticoagulant (NOAC) and an adenosine diphosphate receptor antagonist (P2Y12 inhibitor) vs triple therapy (TT) with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus (DM) patients with co-existing atrial fibrillation (AF) following percutaneous coronary intervention (PCI).
METHODS
Medical Literature Analysis and Retrieval System Online (MEDLINE), http://www.ClinicalTrials.gov, Excerpta Medical data BASE (EMBASE), Web of Science, Cochrane Central and Google Scholar were the searched databases. Studies that were randomized trials or observational studies comparing DT vs TT for the treatment of DM patients with co-existing AF following PCI were included in this analysis. The adverse cardiovascular outcomes and bleeding events were the endpoints. This meta-analysis was carried out by the RevMan version 5.4 software. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent data and interpret the analysis.
RESULTS
A total number of 4970 participants were included whereby 2456 participants were assigned to the DT group and 2514 participants were assigned to the TT group. The enrollment period varied from year 2006 to year 2018. Our current results showed that major adverse cardiac events (RR: 1.00, 95% CI: 0.84-1.20; P = .98), mortality (RR: 1.08, 95% CI: 0.78-1.48; P = .66), myocardial infarction (RR: 1.02, 95% CI: 0.74-1.42; P = .90), stroke (RR: 0.94, 95% CI: 0.53-1.67; P = .84) and stent thrombosis (RR: 1.09, 95% CI: 0.56-2.10; P = .80) were similar with DT versus TT in these patients. However, the risks for total major bleeding (RR: 0.66, 95% CI: 0.54-0.82; P = .0001), total minor bleeding (RR: 0.74, 95% CI: 0.64-0.85; P = .0001), Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding (RR: 0.58, 95% CI: 0.35-0.95; P = .03), TIMI defined minor bleeding (RR: 0.62, 95% CI: 0.42-0.92; P = .02), intra-cranial bleeding (RR: 0.34, 95% CI: 0.13-0.95; P = .04) and major bleeding defined by the International Society on Thrombosis and Hemostasis (RR: 0.68, 95% CI: 0.51-0.90; P = .008) were significantly higher with TT.
CONCLUSIONS
DT with a NOAC and a P2Y12 inhibitor was associated with significantly less bleeding events without increasing the adverse cardiovascular outcomes when compared to TT with aspirin, a P2Y12 inhibitor and a Vitamin K antagonist for the treatment of DM patients with co-existing AF following PCI. Hence, DT is comparable in efficacy, but safer compared to TT. This interesting hypothesis will have to be confirmed in future studies.
Topics: 4-Hydroxycoumarins; Aged; Aspirin; Atrial Fibrillation; Diabetes Mellitus; Diabetic Cardiomyopathies; Drug Therapy, Combination; Female; Hematologic Agents; Humans; Indenes; Male; Observational Studies as Topic; Percutaneous Coronary Intervention; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin K
PubMed: 33847681
DOI: 10.1097/MD.0000000000025546 -
Medicine Feb 2021Exercise test (ET) may have adverse effects on platelet function and induce acute thrombotic events in patients with coronary artery disease (CAD). The aim of this study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Exercise test (ET) may have adverse effects on platelet function and induce acute thrombotic events in patients with coronary artery disease (CAD). The aim of this study is to investigate the platelet function and evaluate the risk of thrombotic events in CAD patients during ET.
METHODS
Pubmed, Embase, Cochrane Library, and Web of Science were searched for a systematic review from initiation to October 2019. The inclusion criteria were controlled clinical trails as study design; investigating platelet function in CAD patients during ET; with ET carried out by treadmill or bicycle ergometer; written in English. Included articles were screened based on title/abstract and full-text review by 2 independent reviewers. Platelet aggregation (PA), platelet surface expression of CD62p and PAC-1, plasma levels of platelet factor 4 (PF4) and beta-thromboglobulin (β-TG) were evaluated before and after ET.
RESULTS
Eighteen articles were included out of the 427 references initially identified. In most of the studies included ET was terminated because of limited symptoms. Prior to ET, no difference in platelet aggregation was observed in CAD patients compared with healthy controls in majority of the studies, with or without the treatment with Aspirin. Dual anti-platelet therapy suppressed adenosine diphosphate (ADP)-induced platelet aggregation at rest. After ET, platelet aggregation, the serum levels of β-thromboglobulin were found unchanged in majority of studies and platelet factor-4 were found unchanged in half of studies. The expression of platelet surface markers were elevated by ET in a few study.
CONCLUSION
Symptom-limited exercise test did not affect platelet function in patients with coronary artery disease; however exercise to higher intensity may induce platelet activation.
Topics: Cardiac Rehabilitation; Coronary Artery Disease; Exercise Test; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests
PubMed: 33663130
DOI: 10.1097/MD.0000000000024932 -
Frontiers in Oncology 2020The efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer...
The efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer remains unclear. We conducted a meta-analysis to assess the benefits and safety of PARPi maintenance therapy in patients with newly diagnosed advanced ovarian cancer. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), which assessed the efficacy of PARPi as a maintenance therapy for newly diagnosed advanced ovarian cancer. Progression-free survival (PFS) was the primary endpoint, which was assessed using hazard ratios (HRs) with 95% confidence intervals (95% CI). Progression-free survival was extracted independently, and the pooled results were used to compare the prognoses of patients who received PARPi maintenance therapy and those who received a placebo. Three RCTs, SOLO1, VELIA/GOG-3005, and PRIMA, which included 1,881 patients with newly diagnosed advanced ovarian cancer, were included in the meta-analysis. The overall analysis showed that PARPi maintenance therapy significantly increased PFS (HR, 0.51; 95% CI, 0.33-0.80; = 0.004) compared to placebo. Subgroup analyses confirmed this result. We also observed an improved PFS in patients with homologous recombination deficiency (HR, 0.50; 95% CI, 0.38-0.66; < 0.001) and in patients with BRCA mutations (HR, 0.42; 95% CI, 0.31-0.57; < 0.001). Moreover, there were no significant differences in health-related quality of life between the PARPi and placebo groups. Patients with newly diagnosed advanced ovarian cancer who received PARPi maintenance therapy had a better prognosis than did those who received a placebo. Moreover, no significant changes in health-related quality of life were seen in PARPi-treated individuals.
PubMed: 32850351
DOI: 10.3389/fonc.2020.01204 -
World Journal of Surgical Oncology Jul 2020The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer.
METHODS
The meta-analysis searched the PubMed, Web of Science, EBSCO, and Cochrane libraries from inception to February 2020 to identify relevant studies. And the main results of this study were long-term prognosis and treatment-related adverse events.
RESULTS
The results showed that the addition of PARP inhibitors could significantly prolong progression-free survival (PFS) and overall survival (OS) for patients with ovarian cancer (HR 0.44, 95% CI 0.34-0.53, p < 0.001; HR, 0.79, 95% CI 0.65-0.94, p < 0.001, respectively). In the BRCA 1/2 mutation patients, the HR of PFS was 0.29 (p < 0.001), and the HR was 0.51 (p < 0.001) in the no BRCA 1/2 mutation patients. The HR of PFS was 0.40 (p < 0.001) in the homologous recombination deficiency (HRD) mutation patients, while the HR was 0.80 (p < 0.001) in the no HRD mutation patients. Moreover, the analysis found that the use of PARP inhibitors did not significantly increase the risk of all grade adverse events (AEs) (RR = 1.04, p = 0.16). But the incidence of grade 3 or higher AEs was increased (RR = 1.87, p = 0.002). In general, the AEs were mainly manifested in the blood system.
CONCLUSIONS
PARP inhibitors can improve the prognosis of ovarian cancer patients with and without genetic mutations (BRCA 1/2 or HRD). Furthermore, PARP inhibitors were tolerable to patients when added to their current therapy, although it inevitably adds the grade 3 and higher AEs.
Topics: Adenosine Diphosphate Ribose; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Prognosis
PubMed: 32622363
DOI: 10.1186/s12957-020-01931-7 -
Archives of Academic Emergency Medicine 2020Currently, the basis of acute coronary syndrome (ACS) therapy is dual antiplatelet therapy (DAPT) with Aspirin as a nonsteroidal anti-inflammatory drug and clopidogrel... (Review)
Review
INTRODUCTION
Currently, the basis of acute coronary syndrome (ACS) therapy is dual antiplatelet therapy (DAPT) with Aspirin as a nonsteroidal anti-inflammatory drug and clopidogrel as adenosine diphosphate receptor antagonists. Therefore, the aim of the present systematic review is to answer that should DAPT with Aspirin and clopidogrel be continued until coronary artery bypass grafting (CABG) in patients who have ACS?
METHODS
The search for relevant studies in the present meta-analysis is based on three approaches: A) systematic searches in electronic databases, B) manual searches in Google and Google Scholar, and C) screening of bibliography of related original and review articles. The endpoints included mortality rate, myocardial infarction (MI), cerebrovascular accident (CVA), reoperation, re-exploration, other cardiac events, renal failure, length of ICU and hospital stay, chest tube drainage and blood product transfusion after CABG.
RESULTS
After the initial screening, 41 articles were studied in detail, and finally the data of 15 studies were included in the meta-analysis. DAPT before CABG in patients with ACS does not increase the rate of mortality, CVA, renal failure, MI, and other cardiac events, but increases reoperation, re-exploration, length of ICU, and hospital stay. Chest tube drainage and blood product transfusion rate significantly increased in the DAPT group compared to the control group (non-antiplatelet or Aspirin alone). Increase in chest tube drainage and blood product transfusion rate indicates an increase in bleeding, so increase in reoperation, re-exploration to control bleeding, and, subsequently, increase in the length of ICU and hospital stay are expected.
CONCLUSIONS
DAPT with Aspirin and clopidogrel before CABG in patients with ACS does not increase the rate of mortality, CVA, renal failure, MI, and other cardiac events despite more bleedings, and it may be suggested before CABG for better graft patency.
PubMed: 32613203
DOI: No ID Found -
Orthopaedic Journal of Sports Medicine Apr 2020Platelet-rich plasma (PRP) has wide applications in orthopaedic care. Its beneficial effects are attributed to the growth factor profile from the platelet secretome. In... (Review)
Review
BACKGROUND
Platelet-rich plasma (PRP) has wide applications in orthopaedic care. Its beneficial effects are attributed to the growth factor profile from the platelet secretome. In theory, these effects would be diminished by medications that inhibit platelet activation and/or the subsequent release of growth factors.
PURPOSE
To determine whether commonly used antiplatelets, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulant medications affect platelet growth factor release in PRP.
STUDY DESIGN
Systematic review; Level of evidence, 2.
METHOD
A systematic review of the literature related to antiplatelet, anti-inflammatory, and anticoagulant drugs was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We used the Downs and Black objective quality scoring system. The literature search consisted of PubMed and Cochrane Library databases. Search terms consisted of 1 item selected from "platelet-rich plasma," "platelet-derived growth factor," and "platelet-rich plasma AND growth factor" combined with 1 item from "antiplatelet," "aspirin," "anticoagulant," and "NSAID." Only studies published within the past 25 years were included.
RESULTS
A total of 15 studies met the inclusion criteria: 7 studies detected no significant decrease in growth factors or mitogenesis, whereas 6 detected a decrease with antiplatelet agents, 1 detected mixed results with an antiplatelet agent, and 1 had mixed results with an antiplatelet agent/vasodilator. In terms of PRP activation, all 3 studies assessing collagen, the 2 studies analyzing adenosine diphosphate alone, and the 1 study investigating arachidonic acid found a decrease in growth factor concentration.
CONCLUSION
Antiplatelet medications may decrease the growth factor release profile in a cyclooxygenase 1- and cyclooxygenase 2-dependent manner. Eight of 15 studies found a decrease in growth factors or mitogenesis. However, more studies are needed to comprehensively understand antiplatelet effects on the PRP secretome.
PubMed: 32426401
DOI: 10.1177/2325967120912841 -
Cardiovascular Diabetology Jan 2019Carotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates... (Meta-Analysis)
Meta-Analysis
Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis.
BACKGROUND
Carotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates the comparative efficacies of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on cIMT progression.
METHODS
We conducted a network meta-analysis (NMA) to evaluate the relative efficacies of several drug classes in modifying cIMT progression. After a literature search in several electronic databases, studies were selected by following predetermined eligibility criteria. An inverse variance-heterogeneity model was used for NMA. Sensitivity analyses were performed to check the reliability of the overall NMA, and transitivity analyses were performed to examine the effects of modifiers on the NMA outcomes.
RESULTS
Data were taken from 47 studies (15,721 patients; age: 60.2 years [95% confidence interval (CI) 58.8, 61.6]; BMI: 27.2 kg/m [95% CI 26.4, 28.0]; and gender: 58.3% males [95% CI 48.3, 68.3]). Treatment duration was 25.8 months [95% CI 22.9, 28.7]. Of the 13 drug classes in the network, treatment with phosphodiesterase III inhibitors was the most effective in retarding annual mean cIMT against network placebo (weighted mean difference (WMD) - 0.059 mm [95% CI - 0.099, - 0.020) followed by the calcium channel blockers (WMD - 0.055 mm [95% CI - 0.099, 0.001]) and platelet adenosine diphosphate inhibitors (WMD - 0.033 mm [95% CI - 0.058, 0.008]). These 3 drug classes also attained the same positions when the NMA was conducted by using first-year changes in mean cIMT. In transitivity analyses, longer treatment duration, higher body mass index (BMI), and a higher baseline cIMT were found to be independently associated with a lesser reduction in annual mean cIMT. However, in a multivariate analysis with these 3 modifiers, none of these factors was significantly associated with annual change in mean cIMT. In the placebo group, age was inversely associated with annual change in mean cIMT independently.
CONCLUSION
Phosphodiesterase III inhibitors and calcium channel blockers are found more effective than other drug classes in retarding cIMT progression. Age, BMI, and baseline cIMT may have some impact on these outcomes.
Topics: Antihypertensive Agents; Calcium Channel Blockers; Carotid Artery Diseases; Carotid Intima-Media Thickness; Disease Progression; Female; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Male; Middle Aged; Phosphodiesterase 3 Inhibitors; Platelet Aggregation Inhibitors; Predictive Value of Tests; Time Factors; Treatment Outcome
PubMed: 30700294
DOI: 10.1186/s12933-019-0817-1 -
European Review For Medical and... Oct 2017Dual antiplatelet therapy (DAPT) is the treatment of choice in the medical management of patients with acute coronary syndrome (ACS). The combination of aspirin and a... (Review)
Review
OBJECTIVE
Dual antiplatelet therapy (DAPT) is the treatment of choice in the medical management of patients with acute coronary syndrome (ACS). The combination of aspirin and a P2Y12 inhibitor in patients who receive a coronary stent reduces the rate of stent thrombosis and the rates of major adverse cardiovascular events. However, patients with acute coronary syndrome remain at risk of recurrent cardiovascular events despite the advance of medical therapy. The limitations of clopidogrel with variable antiplatelet effects and delayed onset of action are well established and lead to the development of newer P2Y12 inhibitors. Prasugrel is a selective adenosine diphosphate (ADP) receptor antagonist indicated for use in patients with ACS. Prasugrel provides greater inhibition of platelet aggregation than clopidogrel and has a rapid onset of action. We have conducted a systematic review to retrieve current evidence regarding the role of prasugrel in the management of ACS. Evidence comparing prasugrel, clopidogrel, and ticagrelor remain scant.
MATERIALS AND METHODS
A complete literature survey was performed using PubMed database search to gather available information regarding management of acute coronary syndromes and prasugrel. An explorative comparison of the safety and efficacy of prasugrel, clopidogrel, and ticagrelor was also conducted.
RESULTS
Prasugrel and ticagrelor are more efficacious than clopidogrel in reducing the occurrence of non-fatal myocardial infarction, stroke, or cardiovascular (CV) death but they have also an increased risk of major bleeding in comparison to clopidogrel.
CONCLUSIONS
Prasugrel and ticagrelor are today the recommended first-line agents in patients with ACS. The estimation of which drug is superior over the other cannot be reliably established from the current trials.
Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thrombosis; Ticlopidine
PubMed: 29131238
DOI: No ID Found