scholarly journals Impact of acetylsalicylic acid on primary prevention of cardiovascular diseases: A meta-analysis of randomized trials

2018 ◽  
Vol 26 (7) ◽  
pp. 746-749 ◽  
Author(s):  
Sunil Upadhaya ◽  
Seetharamprasad Madala ◽  
Ramkaji Baniya ◽  
Kalyan Saginala ◽  
Jahangir Khan

Numerous studies have investigated use of acetylsalicylic acid (ASA) for prevention of cardiovascular deaths. The vast majority of the work in this area has focused on secondary prevention. However, underuse of ASA still remains a major issue. Fewer studies have investigated the impact of ASA on primary prevention of cardiovascular death. A meta-analysis of individual participant data from six randomized studies, published in 2009, showed decrease in serious vascular events but at the cost of causing increased bleeding and hemorrhagic stroke. Recent studies have raised a number of key questions regarding the benefits and risks of using ASA for primary prevention.

2019 ◽  
Vol 72 (8) ◽  
pp. 1426-1436
Author(s):  
Justyna Rosińska ◽  
Joanna Maciejewska ◽  
Robert Narożny ◽  
Wojciech Kozubski ◽  
Maria Łukasik

Introduction: Elevated concentrations of platelet-derived microvesicles are found in cerebrovascular diseases. The impact of acetylsalicylic acid on these microvesicles remains inconsistent, despite its well-established effect on platelet aggregation. High residual platelet aggregation is defined as high on-treatment platelet reactivity, while “treatment failure” is the occurrence of vascular events despite antiplatelet treatment. The aim of this study was to determine whether the antiaggregatory effect of acetylsalicylic acid correlates with platelet-derived microvesicles in convalescent ischaemic stroke patients and cardiovascular risk factor controls as well as to evaluate the association between high on-treatment platelet reactivity and recurrent vascular events with the studied platelet-derived microvesicle parameters. Materials and methods: The study groups consisted of 76 convalescent stroke patients and 74 controls. Total platelet-derived microvesicles, annexino-positive microvesicles number, and platelet-derived microvesicles with surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, GPIIb/IIIa) markers were characterized and quantified using flow cytometry. Cyclooxygenase-1-specific platelet responsiveness, with whole blood impedance platelet aggregation under arachidonic acid stimulation and the serum concentration of thromboxane B2, were evaluated. Results: Neither acetylsalicylic acid intake nor modification of its daily dose caused statistically significant differences in the studied microvesicle parameters. Additionally, no statistically significant differences in the studied microvesicle parameters were revealed between high on-treatment platelet reactivity and non-high on-treatment platelet reactivity subjects in either study subgroup. However, elevated concentrations of PAC-1+/CD61+, CD62P+/CD61+ and CD31+/CD61+ microvesicles were found in stroke patients with treatment failure, defined in this study as a recurrent vascular events in a one-year follow-up period. Conclusions: This study revealed no relationship between circulating microvesicle number and platelet aggregation. The procoagulant and proinflammatory phenotype of circulating platelet-derived microvesicles might contribute to acetylsalicylic acid treatment failure.


2016 ◽  
Vol 84 (1-2) ◽  
Author(s):  
Pierfranco Terrosu

<p>The net clinical benefit of aspirin in primary prevention is uncertain as the reduction in occlusive events needs to be balanced against the increase in gastro-intestinal and cerebral bleedings. The meta-analysis of ATT (Anti Thrombotic Trialists) Collaboration in 2009 showed that aspirin therapy in primary prevention was associated with 12% reduction in cardio-vascular events, due mainly to a reduction in non-fatal myocardial infarction (0.18% vs 0.23% per year, p&lt;0.0001). However, the benefit in term of coronary events was almost balanced by the increase in major bleedings. The balance between potential benefit and harm of aspirin differs in each person and appears to be favorable in subjects at higher cardio-vascular risk. Older people have increased risk of hemorrhage as well as increased risk of heart attack and stroke. As a consequence, it is important consider both likelihoods of benefits as well as harm within the lifespan and functioning of the person. The older people who most likely benefit from aspirin in primary prevention are those at higher cardio-vascular risk, with preserved functional abilities, low comorbidity, low risk of bleeding and a prolonged life expectancy.</p><p> </p><p><strong>Riassunto</strong></p><p>Il beneficio clinico netto dell’aspirina in prevenzione primaria è poco chiaro, a causa del bilancio critico tra riduzione delle occlusioni vascolari e aumento dei sanguinamenti gastro-intestinali e cerebrali. La metanalisi del 2009 del ATT (Anti Thrombotic Trialists) Collaboration mostra che l’aspirina in prevenzione primaria determina una riduzione del 12% degli eventi cardiovascolari, principalmente dovuta ad una riduzione dell’infarto miocardico non-fatale (0.18% vs 0.23% per anno, p&lt;0.0001). Tuttavia il beneficio in termini di eventi coronarici è controbilanciato dall’incremento dei sanguinamenti maggiori. Ne deriva che il bilancio tra vantaggi ed effetti avversi differisce nel singolo soggetto ed appare potenzialmente favorevole nei casi a più elevato rischio cardiovascolare. Nella popolazione anziana è aumentato sia il rischio trombotico che quello emorragico. Di conseguenza, è importante considerare il rapporto rischio/beneficio in relazione alla aspettativa di vita e alla capacità funzionale. In sostanza gli anziani che possono trarre vantaggio dall’aspirina in prevenzione primaria sono quelli a più alto rischio cardiovascolare, con mobilità conservata, scarsa comorbidità, basso rischio emorragico e lunga aspettativa di vita.</p>


2015 ◽  
Vol 114 (11) ◽  
pp. 876-882 ◽  
Author(s):  
Francesca Santilli ◽  
Pasquale Pignatelli ◽  
Francesco Violi ◽  
Giovanni Davì

SummaryType 2 diabetes mellitus is characterised by persistent thromboxane (TX)-dependent platelet activation, regardless of disease duration. Low-dose aspirin, that induces a permanent inactivation of platelet cyclooxygenase (COX)-1, thus inhibiting TXA2 biosynthesis, should be theoretically considered the drug of choice. The most up-to-date meta-analysis of aspirin prophylaxis in this setting, which includes three trials conducted in patients with diabetes and six other trials in which such patients represent a subgroup within a broader population, reported that aspirin is associated with a non-significant decrease in the risk of vascular events, although the limited amount of available data precludes a precise estimate of the effect size. An increasing body of evidence supports the concept that less-than-expected response to aspirin may underlie mechanisms related to residual platelet hyper-reactivity despite anti-platelet treatment, at least in a fraction of patients. Among the proposed mechanisms, the variable turnover rate of the drug target (platelet COX-1) appears to represent the most convincing determinant of the inter-individual variability in aspirin response. This review intends to develop the idea that the understanding of the determinants of less-than-adequate response to aspirin in certain individuals, although not changing the paradigm of the indication to low-dose aspirin prescription in primary prevention, may help identifying, in terms of easily detectable clinical or biochemical characteristics, individuals who would attain inadequate protection from aspirin, and for whom different strategies should be challenged.


2019 ◽  
Vol 23 (25) ◽  
pp. 1-98 ◽  
Author(s):  
Rod S Taylor ◽  
Sarah Walker ◽  
Oriana Ciani ◽  
Fiona Warren ◽  
Neil A Smart ◽  
...  

Background Current national and international guidelines on the management of heart failure (HF) recommend exercise-based cardiac rehabilitation (ExCR), but do not differentiate this recommendation according to patient subgroups. Objectives (1) To obtain definitive estimates of the impact of ExCR interventions compared with no exercise intervention (control) on mortality, hospitalisation, exercise capacity and health-related quality of life (HRQoL) in HF patients; (2) to determine the differential (subgroup) effects of ExCR in HF patients according to their age, sex, left ventricular ejection fraction, HF aetiology, New York Heart Association class and baseline exercise capacity; and (3) to assess whether or not the change in exercise capacity mediates for the impact of the ExCR on final outcomes (mortality, hospitalisation and HRQoL), and determine if this is an acceptable surrogate end point. Design This was an individual participant data (IPD) meta-analysis. Setting An international literature review. Participants HF patients in randomised controlled trials (RCTs) of ExCR. Interventions ExCR for at least 3 weeks compared with a no-exercise control, with 6 months’ follow-up. Main outcome measures All-cause and HF-specific mortality, all-cause and HF-specific hospitalisation, exercise capacity and HRQoL. Data sources IPD from eligible RCTs. Review methods RCTs from the Exercise Training Meta-Analysis of Trials for Chronic Heart Failure (ExTraMATCH/ExTraMATCH II) IPD meta-analysis and a 2014 Cochrane systematic review of ExCR (Taylor RS, Sagar VA, Davies EJ, Briscoe S, Coats AJ, Dalal H, et al. Exercise-based rehabilitation for heart failure. Cochrane Database Syst Rev 2014;4:CD003331). Results Out of the 23 eligible RCTs (4398 patients), 19 RCTs (3990 patients) contributed data to this IPD meta-analysis. There was a wide variation in exercise programme prescriptions across included studies. Compared with control, there was no statistically significant difference in pooled time-to-event estimates in favour of ExCR, although confidence intervals (CIs) were wide: all-cause mortality had a hazard ratio (HR) of 0.83 (95% CI 0.67 to 1.04); HF-related mortality had a HR of 0.84 (95% CI 0.49 to 1.46); all-cause hospitalisation had a HR of 0.90 (95% CI 0.76 to 1.06); and HF-related hospitalisation had a HR of 0.98 (95% CI 0.72 to 1.35). There was a statistically significant difference in favour of ExCR for exercise capacity and HRQoL. Compared with the control, improvements were seen in the 6-minute walk test (6MWT) (mean 21.0 m, 95% CI 1.57 to 40.4 m) and Minnesota Living with Heart Failure Questionnaire score (mean –5.94, 95% CI –1.0 to –10.9; lower scores indicate improved HRQoL) at 12 months’ follow-up. No strong evidence for differential intervention effects across patient characteristics was found for any outcomes. Moderate to good levels of correlation (R 2 trial > 50% and p > 0.50) between peak oxygen uptake (VO2peak) or the 6MWT with mortality and HRQoL were seen. The estimated surrogate threshold effect was an increase of 1.6 to 4.6 ml/kg/minute for VO2peak. Limitations There was a lack of consistency in how included RCTs defined and collected the outcomes: it was not possible to obtain IPD from all includable trials for all outcomes and patient-level data on exercise adherence was not sought. Conclusions In comparison with the no-exercise control, participation in ExCR improved the exercise and HRQoL in HF patients, but appeared to have no effect on their mortality or hospitalisation. No strong evidence was found of differential intervention effects of ExCR across patient characteristics. VO2peak and 6MWT may be suitable surrogate end points for the treatment effect of ExCR on mortality and HRQoL in HF. Future studies should aim to achieve a consensus on the definition of outcomes and promote reporting of a core set of HF data. The research team also seeks to extend current policies to encourage study authors to allow access to RCT data for the purpose of meta-analysis. Study registration This study is registered as PROSPERO CRD42014007170. Funding The National Institute for Health Research Health Technology Assessment programme.


2020 ◽  
Vol 5 ◽  
pp. 14-26 ◽  
Author(s):  
Sunil Pasricha ◽  
Smita Asthana ◽  
Satyanarayana Labani ◽  
Uma Kailash ◽  
Abhinav Srivastav ◽  
...  

Objective: The ASCO/CAP guidelines for reporting HER2 in breast cancer, first released in 2007, aimed to standardize the reporting protocol, and were updated in 2013 and 2018, to ensure right treatment. Several studies have analyzed the changes attributed to 2013 updated guidelines, and majority of them found increase in positive and equivocal cases. However, the precise implication of these updated guidelines is still contentious, in spite of the latest update (2018 guidelines) addressing some of the issues. We conducted systematic review and meta- analysis to see the impact of 2013 guidelines on various HER2 reporting categories by both FISH and IHC. Materials and Methods: After extensively searching the pertinent literature, 16 studies were included for the systematic review. We divided our approach in three strategies: (1) Studies in which breast cancer cases were scored for HER2 by FISH or IHC as a primary test concurrently by both 2007 and 2013 guidelines, (2) Studies in which HER2 results were equivocal by IHC and were followed by reflex-FISH test by both 2007 and 2013 guidelines, and (3) Studies in which trends of HER2 reporting were compared in the two periods before and after implementation of updated 2013 guidelines. All the paired data in these respective categories was pooled and analyzed statistically to see the overall impact of the updated guidelines. Results: In the first category, by pooled analysis of primary FISH testing there has been a significant increase in the equivocal cases (P < 0.001) and positive cases (P = 0.037). We also found 8.3% and 0.8% of all the negative cases from 2007 guidelines shifted to equivocal and positive categories, respectively. Similarly by primary IHC testing there has been a significant increase in both equivocal cases (P < 0.001) and positive cases (P = 0.02). In the second category of reflex-FISH testing there was a substantial increase in the equivocal cases (P < 0.0001); however there is insignificant decrease (10% to 9.7%; P = 0.66) in the amplified cases. In the third approach for evaluating the trend, with the implementation of 2013 guidelines, there was increase in the equivocal category (P = 0.025) and positive category (P = 0.0088) by IHC. By FISH test also there was significant increase in the equivocal category (P < 0.001) while the increase in the positive category was non-significant (P = 0.159). Conclusions: The updated 2013 guidelines has significantly increased the positive and equivocal cases using primary FISH or IHC test and with further reflex testing, thereby increasing the double equivocal cases and increasing the cost and delaying the decision for definite management. However, whether the additional patients becoming eligible for HDT will derive treatment benefit needs to be answered by further large clinical trials.


2019 ◽  
Vol 15 (1) ◽  
pp. 9-17
Author(s):  
Conor Judge ◽  
Sarah Ruttledge ◽  
Robert Murphy ◽  
Elaine Loughlin ◽  
Sarah Gorey ◽  
...  

Background The benefits of aspirin for primary prevention of stroke are uncertain. Methods We performed a cumulative meta-analysis of trials investigating aspirin for primary prevention of cardiovascular disease with a focus on stroke. We assessed the effects of aspirin on non-fatal stroke, hemorrhagic stroke, non-fatal myocardial infarction, all-cause mortality, cardiovascular mortality, major gastrointestinal bleeding, and an analysis of net clinical effect, in populations without a history of clinical or subclinical cardiovascular disease. Summary of review results Among 11 trials (157,054 participants), aspirin was not associated with a statistically significant reduction in non-fatal stroke (odds ratio, 0.94; 95% CI, 0.85 to 1.04) but was associated with an increased risk of hemorrhagic stroke (odds ratio, 1.29; 95% CI, 1.06 to 1.56). Aspirin was not associated with a statistically significant reduction in all-cause mortality (odds ratio, 0.97; 95% CI, 0.92 to 1.03) or cardiovascular mortality (odds ratio, 0.94; 95% CI, 0.85 to 1.03). Aspirin was associated with a reduction in non-fatal myocardial infarction (odds ratio, 0.80; 95% CI, 0.69 to 0.94) and an increased risk of major gastrointestinal bleeding (odds ratio, 1.83; 95% CI, 1.43 to 2.35). Using equal weighting for non-fatal events and major bleeding, we observed no net clinical benefit with aspirin use for primary prevention. Conclusion Our meta-analysis reports no benefit of aspirin for primary stroke prevention.


2018 ◽  
Author(s):  
Omowunmi Aibana ◽  
Chuan-Chin Huang ◽  
Said Aboud ◽  
Alberto Arnedo-Pena ◽  
Mercedes C. Becerra ◽  
...  

ABSTRACTBackgroundFew studies have evaluated the association between pre-existing vitamin D deficiency (VDD) and incident TB. We assessed the impact of baseline vitamin D on TB risk.MethodsWe assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6751 household contacts of TB patients in Peru. We also conducted a one-stage individual participant data meta-analysis searching PubMed and Embase for studies of vitamin D and TB until December 31, 2017. We included studies that assessed vitamin D before TB diagnosis. We defined VDD as 25–(OH)D <50 nmol/L, insufficiency as 50–75 nmol/L and sufficiency as >75nmol/L. We estimated the association between vitamin D and incident TB using conditional logistic regression in the Peru cohort and generalized linear mixed models in the meta-analysis.FindingsIn Peru, baseline VDD was associated with a statistically insignificant increase in incident TB (aOR 1·70, 95% CI 0·84–3·46; p=0·14). We identified seven studies for the meta-analysis and analyzed 3544 participants. Individuals with VDD and very low vitamin D (<25nmol/L) had increased TB risk (aOR 1·48, 95% CI 1·04–210;p=0· 03 and aOR 2 08, 95% CI 0·88–4·92; p trend=002 respectively). Among HIV-positive patients, VDD and very low vitamin D conferred a 2-fold (aOR 2.18, 95% CI 1· 22–3·90; p=0· 01) and 4-fold (aOR 4·28, 95% CI 0·85–21·44; p trend=0·01) increased risk of TB respectively.InterpretationOur findings suggest vitamin D predicts TB risk in a dose-dependent manner and vitamin D supplementation may play a role in TB prevention.FundingNational Institute of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Dental and Craniofacial Research (NIDCR), Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Foundation, Ujala Foundation, Wyncote Foundation, NIH - Fogarty International Center Program of International Training Grants in Epidemiology Related to AIDS, NIAID Byramjee Jeejeebhoy Medical College HIV Clinical Trials Unit, NIAID’s Baltimore-Washington-India Clinical Trials Unit, National Commission on Biotechnology, the Higher Education Commission, International Research Support Initiative Program of the Higher Education Commission Government of Pakistan, the Bill and Melinda Gates Foundation, and the NIH Fogarty International Center.Research in ContextEvidence before this studyNumerous studies have found lower serum vitamin D levels among patients with active TB disease compared to healthy controls. However, research has not clarified whether low vitamin D increases TB risk or whether TB disease leads to decreased vitamin D levels. We conducted PubMed and Medline searches for all studies available through December 31, 2017 on the association between vitamin D status and TB disease. We included the following keywords: “vitamin D,” “vitamin D deficiency,” “hypovitaminosis D,” “25-hydroxyvitamin D,” “1,25-dihydroxyvitamin D,” “vitamin D2,” “vitamin D3,” “ergocalciferol,” “cholecalciferol,” and “tuberculosis.” We found only seven studies had prospectively evaluated the impact of baseline vitamin D levels on risk of progression to TB disease.We report here the results of a case control study nested within a large prospective longitudinal cohort study of household contacts of TB cases and the results of an individual participant data (IPD) metaanalysis of available evidence on the association between vitamin D levels and incident TB disease.Added value of this studyWe demonstrated that low vitamin D levels predicts risk of future progression to TB disease in a dose-dependent manner.Implications of all the available evidenceThese findings suggest the possibility that vitamin D supplementation among individuals at high risk for developing TB disease might play a role in TB prevention efforts.


Author(s):  
Steve Raoul Noumegni ◽  
Thomas Grangereau ◽  
Arzu Demir ◽  
Luc Bressollette ◽  
Francis Couturaud ◽  
...  

AbstractMany studies from current literature show that cardiovascular diseases in patients with venous thromboembolism (VTE) are more frequent than in the general population without VTE. However, data summarizing the impact of cardiovascular diseases on mortality of patients with VTE are lacking. In this systematic review and meta-analysis, we aimed to determine the frequency and incidence rate of cardiovascular death in patients with VTE. MEDLINE and EMBASE were searched from January 1, 2000 to February 28, 2021. Eligible studies were observational prospective cohort studies including patients with VTE and reporting all causes of death. Cardiovascular death was defined as deaths that result from new or recurrent pulmonary embolism, death due to acute myocardial infarction, sudden cardiac death or heart failure, death due to stroke, death due to cardiovascular procedures or hemorrhage, death due to ruptured aortic aneurysm or aortic dissection and death due to other cardiovascular causes. Random-effect models meta-analysis served to determine all pooled effect size of interest with their 95% confidence interval (CI). Thirteen observational studies enrolling 22,251 patients were identified and included. The mean/median age varied between 49 and 75 years. The proportion of men ranged from 38.3 to 53.2%. The overall pooled frequency of cardiovascular death in patients with VTE was 3.9% (95% CI: 2.5–5.6%), while the overall pooled frequency of all-cause mortality was 12.0% (95% CI: 9.1–15.4%). The pooled proportion of cardiovascular death among all causes of deaths in patients with VTE was 35.2% (95% CI: 22.2–49.3%). The pooled incidence rate of cardiovascular death was 1.92 per 100 patient-years (95% CI: 0–4.1). The frequency of cardiovascular death in patients with VTE was significantly higher than in patients without VTE (risk ratio: 3.85, 95% CI: 2.75–5.39). Based on this updated meta-analysis from 13 prospective cohort studies, cardiovascular death in patients with VTE is more frequent than in the general population without VTE.


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