Hart and colleagues provide an update of a previous meta-analysis of antithrombotic agents for stroke prevention in patients with atrial fibrillation. The updated meta-analysis shows that, compared...

Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)60938-7.pdf

Peptic ulcer disease

This document has been developed by the American College of Cardiology Foundation (ACCF) Task Force on Clinical Expert Consensus Documents, the American College of Gastroenterology (ACG), and the American Heart Association (AHA). Expert consensus documents (ECDs) are intended to inform practitioners, payers, and other interested parties of the opinion of the ACCF and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community. Topics chosen for coverage by ECDs are so designed because the evidence base, the experience with technology, and/or the clinical practice are not considered sufficiently well developed to be evaluated by the formal American College of Cardiology/American Heart Association (ACC/AHA) practice guidelines process. Often the topic is the subject of ongoing investigation. Thus, the reader should view ECDs as the best attempt of the ACCF and other cosponsors to inform and guide clinical practice in areas where rigorous evidence may not be available or the evidence to date is not widely accepted. When feasible, ECDs include indications or contraindications. Topics covered by ECDs may be addressed subsequently by the ACC/AHA Practice Guidelines Committee as new evidence evolves and is evaluated.

The Task Force on ECDs makes every …

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ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents

During the 1980s, the free radical, nitric oxide (NO), was discovered to be a crucial signalling molecule, with wide-ranging functions in the cardiovascular, nervous and immune systems. Aside from providing a credible explanation for the actions of organic nitrates and sodium nitroprusside that have long been used in the treatment of angina and hypertensive crises respectively, the discovery generated great hopes for new NO-based treatments for a wide variety of ailments. Decades later, however, we are still awaiting novel licensed agents in this arena, despite an enormous research effort to this end. This review explores some of the most promising recent advances in NO donor drug development and addresses the challenges associated with NO as a therapeutic agent.

/pdf/recent-developments-in-nitric-oxide-donor-drugs-3fzti6amun.pdf

Recent developments in nitric oxide donor drugs

Background—The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. Methods and Results—We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, ...

Six-Month Versus 12-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents The Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) Randomized, Multicenter Study

Objectives To assess the risk of serious upper gastrointestinal bleeding associated with the newer antithrombotic agents used alone or in combination with other antithrombotic drugs; to describe the trends in use of antithrombotic drugs in the background population. Design Population based case-control study. Setting Funen County, Denmark (population 470 000). Subjects 1443 cases of serious upper gastrointestinal bleeding identified during 2000-4; 57 720 age and sex matched controls. Main outcome measure Exposure to low dose aspirin, clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic treatment. Results Adjusted odds ratios associating drug use with upper gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3 (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for dipyridamole and aspirin. Other combinations were used too infrequently to allow estimation. The number of treatment years needed to produce one excess case varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel alone. During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population. Conclusion Antithrombotic treatment is becoming increasingly aggressive. Combined antithrombotic treatment confers particular risk and is associated with high incidence of gastrointestinal bleeding.

https://www.bmj.com/content/bmj/333/7571/726.full.pdf

Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT



• Recent studies have suggested an increased risk of upper gastrointestinal bleeding (UGB) in spironolactone users.



• We conducted this population-based case–control study to confirm the association between spironolactone use and acute nonvaricose UGB alone or in combination with low-dose aspirin and other antithrombotic drugs.



WHAT THIS STUDY ADDS



• The current use of spironolactone is associated with an increased risk of nonvaricose UGB.



• The effect is most pronounced for cases aged 55–74 years.



• Persons with a high current dose have a higher risk.



• The risk is not modified by high cumulative doses or by concurrent use of antithrombotic or nonsteroidal anti-inflammatory drugs.



AIMS

Recent studies have suggested an increased risk of upper gastrointestinal bleeding (UGB) in spironolactone users. The aim was to confirm the association, identify the risk factors and quantify the absolute risk.



METHODS

A population based case–control study was conducted in the County of Funen, Denmark. Cases (n = 3652) were all subjects with a first discharge diagnosis of serious UGB during the period 1995 to 2006. Age- and gender-matched controls (10 for each case) (n = 36 502) were selected by risk set sampling. Data on all subjects' drug exposure and past medical history were retrieved from a prescription database and from the County's patient register. Confounders were controlled by conditional logistic regression.



RESULTS

The adjusted odds ratio (OR) associating current use of spironolactone with UGB was 2.7 [95% confidence interval (CI) 2.2, 3.2]. The risk increased with higher doses of spironolactone (5.4; 3.4, 8.6) for 100-mg tablets. No trend was found with increasing cumulative dose. The strongest association was found among users aged 55-74 years (OR 13.1; 6.5, 26.3). Current use of loop diuretics was also associated with an increased risk of UGB (1.9; 1.7, 2.1).



CONCLUSION

The use of spironolactone is associated with increased risk of UGB. The risk increases with higher doses.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.2008.03205.x

Spironolactone use and the risk of upper gastrointestinal bleeding: a population-based case-control study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT



• An apparent protective effect of statins against upper gastrointestinal bleeding was postulated in a post hoc analysis of a randomized trial



• We aimed to evaluate the effect of statin use on acute nonvariceal upper gastrointestinal bleeding alone or in combinations with low-dose aspirin and other antithrombotic drugs



WHAT THIS STUDY ADDS



• Our study could not demonstrate an inverse association between use of statins and upper gastrointestinal bleeding



• The lack of effect was consistent across most subgroups, across different cumulative or current doses and different statin substances



• In explorative analyses, there appeared to be protective effect only in users of low-dose aspirin



• There was no interaction with use of other antithrombotic drugs



AIMS Recently, an apparent protective effect of statins against upper gastrointestinal bleeding (UGB) was postulated in a post hoc analysis of a randomized trial We aimed to evaluate the effect of statin use on acute nonvariceal UGB alone or in combinations with low-dose aspirin and other antithrombotic drugs



METHODS A population-based case–control study was conducted in the County of Funen, Denmark Cases (n = 3652) were all subjects with a first discharge diagnosis of serious UGB from a hospital during the period 1995 to 2006 Age- and gender-matched controls (10 for each case) (n = 36 502) were selected by a risk set sampling Data on all subjects' drug exposure and past medical history were retrieved from a prescription database and from the County's patient register Confounders were controlled by conditional logistic regression



RESULTS The adjusted odds ratios (ORs) associating use of statins with UGB were 094 (078–112) for current use, 140 (089–220) for recent use and 142 (096–210) for past use The lack of effect was consistent across most patient subgroups, different cumulative or current statin doses and different statin substances In explorative analyses, a borderline significant protective effect was observed for concurrent users of low-dose aspirin [OR 043 (018–105)]



CONCLUSION Statins do not prevent UGB, except possibly in users of low-dose aspirin

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.2009.03362.x

Do statins protect against upper gastrointestinal bleeding

INTRODUCTION: This paper discusses the optimal distribution of responsibility between general practitioners (GPs) and hospitals for follow-up of patients with chronic diseases. We investigated a set of risk stratification criteria developed to optimize specialist shared care for patients with diabetes mellitus. MATERIAL AND METHODS: We included patients with diabetes from the catchment areas of four diabetes out-patient clinics in southern Denmark. Patients were risk-stratified to 3 follow-up levels (level 1 - follow-up only by their GP, level 2 - intensified follow-up by GP and/or shared care schemes, level 3 - follow-up only in out-patient clinics). The results were subsequently compared with the patients' actual follow-up status. RESULTS: A total of 647 patients (563 type 2 diabetes and 84 type 1 diabetes) were included from 15 GPs. Among these, 139 were stratified to level 1, 409 to level 2 and 99 to level 3. A total of 444 patients were actually being followed by their GP, 129 in shared care and 74 in out-patient clinics. The frequency of out-patient and shared care control varied from 13% to 39% between the four centres. CONCLUSION: Patients generally had a higher risk profile than anticipated. The model could select high-risk patients to be followed in specialized out-patient clinics. The model was less suitable for patients with low or moderate risk, and it should be modified before its general introduction.

Risk stratification of patients with diabetes mellitus

The clinical use of anti-thrombotic agents has shifted towards more aggressive therapy and towards regimes with more than one drug. Data on the risk of upper gastrointestinal bleedings (UGB) with combined anti-thrombotic therapy are scarce. In the period 2000 through 2004, 1,443 cases of serious UGB and 57,720 control subjects were identified in Funen County. Anti-thrombotic therapy is becoming increasingly aggressive. Combined anti-thrombotic therapy confers particular risk and is associated with high incidence rates of GI bleeding.

Brug af antitrombotisk behandling i monoterapi eller kombination og risikoen for øvre gastrointestinal blødning: Et populationsbaseret case-kontrol-studie. Sekundærpublikation

Alin Andries

Papers

Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study

Spironolactone use and the risk of upper gastrointestinal bleeding: a population-based case-control study.

Do statins protect against upper gastrointestinal bleeding

Risk stratification of patients with diabetes mellitus

Brug af antitrombotisk behandling i monoterapi eller kombination og risikoen for øvre gastrointestinal blødning: Et populationsbaseret case-kontrol-studie. Sekundærpublikation