scholarly journals Use and Misuse of Aspirin in Primary Cardiovascular Prevention

2017 ◽  
Vol 11 ◽  
pp. 117954681770214 ◽  
Author(s):  
Sergio Coccheri
Keyword(s):  
Primary Prevention ◽  
Clinical Benefit ◽  
Cardiovascular Prevention ◽  
Bleeding Risk ◽  
Threshold Value ◽  
Low Risk ◽  
Risk Levels ◽  
Net Clinical Benefit ◽  
European Society Of Cardiology ◽  
Meta Analyses

The use of low-dose aspirin in primary prevention of cardiovascular (CV) events in healthy or apparently healthy people is a widely debated topic. Many arguments indicate that “primary prevention” is only a conventional definition and that the transition from primary to secondary prevention represents a continuum of increasing levels of CV risk. Although there are no direct proofs of a different efficacy of aspirin at different CV risk levels, in low-risk populations aspirin will appear to be less efficient. In fact, the lower number of events occurring in patients at low risk yields lower absolute numbers of events prevented. As many as 6 meta-analyses of trials of primary CV prevention with aspirin versus placebo, performed between 2009 and 2016, confirmed the above concepts and showed a concordant, significant reduction in nonfatal myocardial infarction, with no significant effects on stroke, as well as on CV and all-cause mortality. The recent demonstration of a moderate protective effect of aspirin on cancer (especially colorectal) confers, however, additional value to the use of aspirin, although unusually long durations of treatment and optimal daily compliance seem to be necessary. Because aspirin increases the bleeding risk, the evaluation of its net clinical benefit is an important point of debate. Thus, it is justified to search for a cutoff level of global CV risk above which the net clinical benefit of aspirin becomes evident. Such a threshold value has been calculated considering the data of 9 primary prevention trials, by the Thrombosis Group of the European Society of Cardiology, and has been indicated as a risk value of 2 or more major CV events per 100 persons per year. Also, in the recent 2016 US Guidelines, the main criterion adopted for the indication of aspirin is the level of global CV risk (suggested cutoff is 1 or more major CV events per 100 persons per year). Beyond the different values selected, it is seems very important to introduce to clinical practice and future trials a new criterion based on the level of global CV risk.

scholarly journals Ischemic and bleeding risk stratification in diabetic patients after acute coronary syndrome based on insulin requirement

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Cavallari ◽  
E Sagazio ◽  
E Antonucci ◽  
P Calabro' ◽  
F Gragnano ◽  
...  
Keyword(s):  
Insulin Therapy ◽  
Antiplatelet Therapy ◽  
Clinical Benefit ◽  
Dual Antiplatelet Therapy ◽  
Bleeding Risk ◽  
Diabetic Patients ◽  
Coronary Syndrome ◽  
Diabetes Status ◽  
Increased Risk ◽  
Net Clinical Benefit

Abstract Background Diabetes is a known risk factor for a first or recurrent cardiovascular event, however, its association with an increased risk of bleeding is controversial. To date, no study has explored the prognostic weight of insulin therapy in the setting of ACS. Purpose To investigate the differential role of insulin versus no insulin therapy on ischemic and bleeding risks in patients with diabetes and ACS. Methods START-ANTIPLATELET is a prospective, real-world multicenter registry including consecutive patients admitted for ACS. For the purpose of this analysis, patients were stratified according to diabetes status and insulin therapy. We compared 1-year rates of major adverse cardiovascular events, a composite of cardiovascular death, myocardial infarction and stroke, and of any bleeding, according to diabetes status (no diabetes, diabetes not on insulin therapy, diabetes on insulin therapy). In addition, we evaluated the net clinical benefit of dual antiplatelet therapy with the newer P2Y12 inhibitors (ticagrelor or prasugrel) vs dual antiplatelet therapy with clopidogrel according to diabetes status. Results In an overall population of 907 patients, 198 had diabetes, 10.6% of whom were on insulin. From non-diabetic patients to diabetic patients not on insulin and diabetic patients on insulin there was a stepwise decrease of MACE-free survival (log-rank p 0.039) with incidence of events at 1 year being 3.8%, 6.8% (adjusted p vs no diabetes 0.49) and 12.5% (adjusted p vs no diabetes 0.047), respectively (Figure, panel A). The rates of any bleeding were higher in patients on insulin (20.8% vs 8.8% in those without diabetes and 5.8% in diabetic patients not receiving insulin; log-rank p 0.028; Figure, panel B). Multivariable analysis demonstrated an almost 5-fold increase of any bleeding in diabetic patients with vs without insulin (OR 4.98, 95% CI 1.46–16.92; p=0.010). In the overall population, the incidence of the net composite endpoint including MACE or major bleeding with the use of ticagrelor/prasugrel on top of aspirin was significantly lower compared to use of clopidogrel (4.7% vs 8.4%; OR 0.54, 95% CI 0.30–0.94, p=0.031). This net clinical benefit in patients receiving a newer P2Y12 inhibitor was regardless of the diabetes status (p for interaction 0.48). Conclusions In this cohort of ACS patients, the presence of diabetes stratified by insulin therapy was associated with a graded increase in the 1-year rates of MACE. Conversely, insulin therapy significantly contributed to the overall increase of bleeding risk in diabetes. Funding Acknowledgement Type of funding source: None

Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study

2011 ◽  
Vol 106 (10) ◽  
pp. 739-749 ◽  
Author(s):  
Gregory Lip ◽  
Jesper Lindhardsen ◽  
Deirdre Lane ◽  
Ole Ahlehoff ◽  
Morten Hansen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Study ◽  
Clinical Benefit ◽  
Vitamin K Antagonists ◽  
Bleeding Risk ◽  
Chads2 Score ◽  
Risk Of Bleeding ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Net Clinical Benefit

SummaryIt was the aim of this study to determine the efficacy and safety of vitamin K antagonists (VKAs) and acetylsalicylic acid (ASA) in patients with non-valvular atrial fibrillation (AF), with separate analyses according to predicted thromboembolic and bleeding risk. By individual levellinkage of nationwide registries, we identified all patients discharged with non-valvular AF in Denmark (n=132,372). For every patient, the risk of stroke and bleeding was calculated by CHADS2, CHA2DS2-VASc, and HAS-BLED. During follow-up, treatment with VKA and ASA was determined time-dependently. VKA consistently lowered the risk of thromboembolism compared to ASA and no treatment; the combination of VKA+ASA did not yield any additional benefit. In patients at high thromboembolic risk, hazard ratios (95% confidence interval) for thromboembolism were: 1.81 (1.73–1.90), 1.14 (1.06–1.23), and 1.86 (1.78–1.95) for ASA, VKA+ASA, and no treatment, respectively, compared to VKA. The risk of bleeding was increased with VKA, ASA, and VKA+ASA compared to no treatment, the hazard ratios were: 1.0 (VKA; reference), 0.93 (ASA; 0.89–0.97), 1.64 (VKA+ASA; 1.55–1.74), and 0.84 (no treatment; 0.81–0.88), respectively. There was a neutral or positive net clinical benefit (ischaemic stroke vs. intracranial haemorrhage) with VKA alone in patients with a CHADS2 score of ≥ 0, and CHA2DS2-VASc score of ≥ 1. This large cohort study confirms the efficacy of VKA and no effect of ASA treatment on the risk of stroke/thromboembolism. Also, the risk of bleeding was increased with both VKA and ASA treatment, but the net clinical benefit was clearly positive, in favour of VKA in patients with increased risk of stroke/thromboembolism.

scholarly journals Net Clinical Benefit of Edoxaban for Stroke, Mortality, and Bleeding Risk

2016 ◽  
Vol 2 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Andrew D. Blann ◽  
Ron Pisters ◽  
Gregory Y.H. Lip
Keyword(s):  
Clinical Benefit ◽  
Bleeding Risk ◽  
Stroke Mortality ◽  
Net Clinical Benefit

scholarly journals Ischemic Stroke and Bleeding

Stroke ◽  
2020 ◽  
Vol 51 (3) ◽  
pp. 808-814
Author(s):  
Robert J. Stanton ◽  
Mark H. Eckman ◽  
Daniel Woo ◽  
Charles J. Moomaw ◽  
Mary Haverbusch ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Major Bleeding ◽  
Clinical Benefit ◽  
Bleeding Event ◽  
Bleeding Risk ◽  
International Normalized Ratio ◽  
Unique Identifier ◽  
Entire Cohort ◽  
Life Years ◽  
Net Clinical Benefit

Background and Purpose— Patients with intracerebral hemorrhage (ICH) and atrial fibrillation (AF) are at risk for ischemic events. While risk calculators (CHA 2 DS 2 -VASc and HAS-BLED) have been validated to assess risk for ischemic stroke and major bleeding in AF patients, decisions about anticoagulation must consider the net clinical benefit of anticoagulation. Furthermore, stroke and bleeding risk are highly correlated, making decisions more difficult. Methods— We examined patients in the GERFHS III study (Genetic and Environmental Risk Factors for Hemorrhagic Stroke)—a population-based retrospective study of spontaneous ICH patients without a structural or traumatic cause in the Greater Cincinnati/Northern Kentucky region between July 2008 and December 2012. CHA 2 DS 2 -VASc and HAS-B(L)ED (minus L because labile international normalized ratio was unavailable) scores were calculated for ICH patients with AF. Using a Markov state transition model, we estimated net clinical benefit of anticoagulation relative to no treatment in quality-adjusted life years (QALYs). We defined minimal clinically relevant benefit as 0.1 QALYs. Results— Among 1186 cases of spontaneous ICH, 95 cases had AF and met our survival criteria. Within 1 year, 8 of 95 (8%) would be expected to have a major bleeding event on anticoagulation, and 5 of 95 (5%) of patients would be expected to have an ischemic stroke off anticoagulation. Sixty-eight of 95 (71%) patients would have higher risk for major bleeding than for ischemic stroke. Anticoagulation with directly acting anticoagulants would result in no clinically significant gain or loss in 73%. Roughly 12% would gain >0.1 QALYs, and 15% would lose >0.1 QALYs. Among patients receiving aspirin, most have no significant net clinical benefit or loss. Overall, anticoagulation of the entire cohort would result in an aggregate loss of 0.92 QALYs. Conclusions— Our analysis suggests that universal anticoagulation after ICH would be associated with a net loss of QALY. Additional factors should be considered before anticoagulating patients with AF after ICH. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00930280.

Abstract 4016: Does Prasugrel Provide a Clinically Important Treatment Benefit Compared with Clopidogrel? A Bayesian Analysis of TRITON-TIMI 38

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Sanjay Kaul ◽  
Prediman K Shah ◽  
George A Diamond
Keyword(s):  
Bayesian Analysis ◽  
Clinical Benefit ◽  
Statistical Significance ◽  
Clinical Importance ◽  
Minimum Clinically Important Difference ◽  
Threshold Value ◽  
Relative Difference ◽  
Minor Bleeding ◽  
Treatment Benefit ◽  
Net Clinical Benefit

Background: In contrast to the conventional frequentist analysis, the Bayesian method is ideally suited to provide a quantitative estimate of a given magnitude of treatment benefit or harm. Objective: A reappraisal, with emphasis on both statistical significance and clinical importance, of the recently reported TRITON-TIMI 38 trial that compared prasugrel with clopidogrel in ACS patients scheduled for PCI. Methods: Posterior probabilities (Pr) that the relative difference (d) in benefit and risk is greater than the putative threshold value for clinical importance (d>0% to 20%) were derived from a Bayesian analysis using an uninformative or “agnostic” prior (log mean RR, = 0, SD = 2) and empirical evidence from TRITON-TIMI 38. Results (Table ) : Although the Pr(d>0%) and Pr(d>10%) difference in the primary endpoint are 100% and 97.5%, respectively, the Pr(d>20%), the “minimum clinically important difference” that the study was powered to detect, is only 40%. Similar patterns are observed with all-cause death/MI/CVA. The Pr(d>10%) harm (for either TIMI major or TIMI major plus minor bleeding) exceeds 90%, and Pr (d>20%) harm exceeds 65%. The Pr(d>20%) harm exceeds the Pr(d>20%) benefit. Combining ischemic endpoints and TIMI major bleeding into net clinical benefit, the Pr(d>10%) benefit is <80% and Pr(d>20%) benefit is <5%. If TIMI major plus minor bleeding is included, the probability of net clinical benefit with prasugrel therapy is reduced even further (<5% for d>10% and <1% for d>20%). Conclusions: The probability of clinically important benefit associated with prasugrel treatment in TRITON-TIMI 38 is far less than that implied by conventional statistical significance. Bayesian analysis provides a useful tool in quantifying clinically meaningful difference. Ultimately, the clarity of the balance between “clinically important”, not just “statistically significant”, benefit or harm should influence guideline recommendations and treatment decisions. Bayesian Analysis of TRITON-TIMI 38 Trial

Low Molecular Weight Heparin Therapy: Is Monitoring Needed?

1994 ◽  
Vol 72 (03) ◽  
pp. 330-334 ◽  
Author(s):  
B Boneu
Keyword(s):  
Molecular Weight ◽  
Clinical Trials ◽  
Plasma Proteins ◽  
Bleeding Risk ◽  
Heparin Therapy ◽  
Low Molecular Weight ◽  
Vein Thrombosis ◽  
Meta Analyses ◽  
Deep Vein ◽  
Initial Check

SummaryRecent meta-analyses indicate that low molecular weight heparins (LMWH) are more effective than unfractionated heparin (UH) in preventing and treating deep vein thrombosis. This article presents the arguments for and against the need for laboratory monitoring. At the present time, the only tests currently available for monitoring LMWH therapy are those which measure the anti Xa activity in the plasma. Due to lower binding to plasma proteins and to cell surfaces,the plasma anti Xa activity generated by a given dose of LMWH is more predictable than for UH.Some clinical trials suggest that LMWH delivered at the recommended dose expose the patient to less bleeding risk than UH. Several . meta-analyses indicate comparable risk while any overdose unaccept-ably increases the haemorrhagic risk. The lowest dose of LMWH still effective in treating established DVT is presently unknown; some reports indicate that inadequate doses of LMWH are associated with a lack of efficacy for prevention. An overview of the published clinical trials indicates that the LMWH dose has never been monitored for prevention of DVT. In the treatment of established DVT, several trials have been performed without any monitoring, while in others the dose was adapted to target a given anti Xa activity. These considerations suggest that in prevention of DVT, monitoring the dose is not required. In the treatment of established DVT, considering the haemorrhagic risk of LMWH, the risk of undertreating the patient and the absence of large clinical trials comparing the advantages of monitoring the dose or not, it might be useful to check anti Xa activity at least once at the beginning of the treatment but the need for this initial check remains to be established. Because a large proportion of patients will be in the desired range, dose adjustments will be far less frequent than for UH.

Perioperative Management of DOACs in Vascular Surgery: A Practical Approach

2019 ◽  
Vol 24 (38) ◽  
pp. 4518-4524 ◽  
Author(s):  
George Kouvelos ◽  
Miltiadis Matsagkas ◽  
Nikolaos Rousas ◽  
Petroula Nana ◽  
Konstantinos Mpatzalexis ◽  
...  
Keyword(s):  
Vascular Surgery ◽  
Perioperative Management ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Low Risk ◽  
Practical Approach ◽  
Current Evidence ◽  
Thromboembolic Risk ◽  
Specific Data ◽  
Vascular Procedure

Background: Approximately 10–15% of patients on DOACs have to interrupt their anticoagulant before an invasive procedure every year. The perioperative management and monitoring of DOACs have proved to be challenging, as differences in patients’ status and in the invasiveness of each procedure develop different situations that need a tailored therapeutic approach to each patient’s needs. Methods: This review aims to summarize current evidence on the perioperative management of DOACs in patients undergoing a vascular surgical procedure focusing with a practical approach on three key clinical questions: (i) can we stop DOAC therapy before the vascular procedure? (ii) is bridging therapy necessary? and (iii) which is the best perioperative strategy for interruption and resumption of the anticoagulant therapy? Results: No specific data exist for the perioperative management of vascular surgery patients on DOACs, as most studies include low number of such patients. Therapeutic strategy on how to handle DOACs perioperatively must be based on their half-life, the bleeding risk of the invasive procedures, and on the thromboembolic risk of the patient. Renal function plays a crucial role in such situations, increasing thromboembolic and bleeding risk. In general, DOACs should be stopped 2 days for high bleed risk, 1 day for low risk and should be resumed 48-72 hrs after high risk, 24 hrs after low-risk procedure. Bridging is almost never needed. Conclusion: Further perioperative research studies on patients undergoing vascular surgery are needed to confirm whether currently accepted therapeutic perioperative strategy is appropriate for these patients.

scholarly journals Meta-regression of randomized control trials with antithrombotics: weak correlation between net clinical benefit and all cause-mortality

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Roubi Kilo ◽  
Silvy Laporte ◽  
Rama Arab ◽  
Sabine Mainbourg ◽  
Steeve Provencher ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Surrogate Endpoint ◽  
Weak Correlation ◽  
Surrogate Outcome ◽  
Randomized Controlled ◽  
Relative Risks ◽  
All Cause Mortality ◽  
Prevention Studies ◽  
Randomized Control ◽  
Net Clinical Benefit

AbstractThis study aimed to explore the validity of the use of the net clinical benefit (NCB), i.e. the sum of major bleeding and thrombotic events, as a potential surrogate for all-cause mortality in clinical trials assessing antithrombotics. Published randomized controlled trials testing anticoagulants in the prevention or treatment of venous thromboembolism (VTE) and non-valvular atrial fibrillation (NVAF) were systematically reviewed. The validity of NCB as a surrogate endpoint was estimated by calculating the strength of correlation of determination (R2) and its 95% confidence interval (CI) between the relative risks of NCB and all-cause mortality. Amongst the 125 trials retrieved, the highest R2trial values were estimated for NVAF (R2trial = 0.41, 95% CI [0.03; 0.48]), and acute VTE (R2trial = 0.30, 95% CI [0.04; 0.84]). Conversely, the NCB did not correlate with all-cause mortality in prevention studies with medical (R2trial = 0.12, 95% CI [0.00; 0.36]), surgical (R2trial = 0.05, 95% CI [0.00; 0.23]), and cancer patients (R2trial = 0.006, 95% CI [0.00; 1.00]). A weak correlation between NCB and all cause-mortality was found in NVAF and acute VTE, whereas no correlation was observed in clinical situations where the mortality rate was low. Consequently, NCB should not be considered a surrogate outcome for all cause-mortality in anticoagulation trials.

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