Tag: aspirin

Aspirin as Effective as Heparin for Clot Prevention in Bone Fracture Hospitalisation

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Patients hospitalised with fractures typically receive low-molecular-weight heparin to prevent life-threatening blood clots. A new clinical trial, however, found that inexpensive over-the-counter aspirin is just as effective. The findings, published today in the New England Journal of Medicine, may lead surgeons to change their practice and administer aspirin to these patients.

With more than 12 000 patients, the multi-centre randomised clinical trial is the largest trial ever conducted on orthopaedic trauma patients. This multidisciplinary collaboration between orthopaedic surgeons and trauma surgeons points to the importance of evaluating techniques used to prevent post-surgical complications, like blood clots and infections, through high-quality, head-to-head comparison studies.

“Many patients with fractures will likely strongly prefer to take a daily aspirin over receiving injections after we found that both give them similar outcomes for prevention of the most serious outcomes from blood clots,” said the study’s principal investigator Robert V. O’Toole, MD. “We expect our findings from this large-scale trial to have an important impact on clinical practice that may even alter the standard of care.”

Patients who experience fractures that require surgery are at increased risk of developing blood clots, including life-threatening pulmonary embolisms. Current guidelines recommend prescribing low-molecular-weight heparin (enoxaparin) to prevent these clots, although smaller clinical trials in total joint replacement surgery suggested a potential benefit of aspirin as a less-expensive, widely available option.

The study enrolled 12 211 patients with leg or arm fractures that necessitated surgery or pelvic fractures regardless of the treatment. Half were randomised to 30mg of injectable enoxaparin twice daily. The other half received 81mg of aspirin twice daily. Patients were followed for 90 days to measure health outcomes from the two treatments.

The main finding of the study was that aspirin was “non-inferior,” or no worse than low molecular-weight heparin in preventing death from any cause – 47 patients in the aspirin group died, compared with 45 patients in the heparin group. For other important complications, the researchers also found no differences in pulmonary embolisms between the two groups. The incidence of bleeding complications, infection, wound problems, and other adverse events from the treatments was also similar in both groups.

Of all the outcomes studied, the only potential difference noted was in deep vein thrombosis. This condition was relatively uncommon in both groups as it occurred in 2.5% of patients in the aspirin group, and in 1.7% of patients in the heparin group.

“This relatively small difference was driven by clots lower in the leg, which are thought to be of less clinical significance and often do not require treatment,” said study co-principal investigator Deborah Stein, MD, MPH.

“Many patients don’t like giving themselves injections. It’s not fun in terms of giving the actual injection because it burns, and your stomach tends to bruise more easily compared to aspirin,” said Debra Marvel, a 53-year-old from Columbia, MD, who served as a patient advisor on the study. She received Lovenox (low-molecular-weight heparin) after her legs were crushed in a 2015 pedestrian accident, requiring multiple surgeries at the University of Maryland Shock Trauma Center. “Patients also prefer aspirin because Lovenox can be expensive based on insurance.”

“An estimated one million Americans are hospitalised each year with extremity fractures, and this new finding could help prevent potentially fatal blood clots in these patients using a medication that is cheaper and far easier to administer,” said Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “Given these important results, we can expect the guidelines for the prevention of blood clots to be revised to include the option of aspirin for patients with traumatic bone fractures.”

Source: University of Maryland School of Medicine

Antibiotics Reduce the Gastrointestinal Bleeding Risk of Long-term Aspirin

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A major clinical trial found that the risk of gastrointestinal bleeding caused by long-term aspirin use can be reduced with a short course of antibiotics, potentially improving the safety of aspirin when used to prevent heart attacks, strokes and possibly some cancers.

The results of the HEAT (Helicobacter pylori Eradication Aspirin) trial, which was led by Professor Chris Hawkey from the University of Nottingham, are published in The Lancet.

Aspirin in low doses is a very useful preventative drug in people at high risk of strokes or heart attacks. However, on rare occasions, its blood thinning effect can provoke internal ulcer bleeding. These ulcers may be caused by Helicobacter pylori.

The STAR (Simple Trials for Academic Research) team from the University of Nottingham investigated whether a short course of antibiotics to remove these bacteria would reduce the risk of bleeding in aspirin users.

The HEAT trial, conducted in 1208 UK general practices, was a real-life study which used clinical data routinely stored in GP and hospital records, instead of bringing patients back for follow up trial visits.

The researchers recruited 30 166 who were taking aspirin. Those who tested positive for H. pylori were randomised to receive antibiotics or placebos (dummy tablets) and were followed for up to 7 years.

Over the first two and a half years, those who had antibiotic treatment were less likely to be hospitalised for ulcer bleeding than those taking placebo (6 versus 17). Protection occurred rapidly: with the placebo group, the first hospitalisation for ulcer bleeding occurred after 6 days, compared to 525 days following antibiotic treatment.

Over a longer time period, protection appeared to wane. However, the overall rate of hospitalisation for ulcer bleeding was lower than expected and this in line with other evidence that ulcer disease is on the decline. Risks for people already on aspirin are low. Risks are higher when people first start aspirin, when searching for H. pylori and treating it is probably worthwhile.

Aspirin has many benefits in terms of reducing the risk of heart attacks and strokes in people at increased risk. There is also evidence that it is able to slow down certain cancers. The HEAT trial is the largest UK-based study of its kind, and we are pleased that the findings have shown that ulcer bleeding can be significantly reduced following a one-week course of antibiotics. The long-term implications of the results are encouraging in terms of safe prescribing.

Professor Chris Hawkey, University of Nottingham’s School of Medicine and Nottingham Digestive Diseases Centre

Source: University of Nottingham

With Warfarin, Dropping Aspirin Reduces Bleeding Complications for Some

Red blood cells
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Research from Michigan Medicine suggests that, for venous thromboembolism (VTE) or atrial fibrillation (AF) patients without a history of heart disease who are taking warfarin, stopping aspirin use causes their risk of bleeding complications to drop significantly.

For the study, which is published in JAMA Network Open, researchers analysed over 6700 people treated at anticoagulation clinics across Michigan for VTE as well as AF. Patients were treated with warfarin but also took aspirin despite not having history of heart disease.

“We know that aspirin is not a panacea drug as it was once thought to be and can in fact lead to more bleeding events in some of these patients, so we worked with the clinics to reduce aspirin use among patients for whom it might not be necessary,” said senior study author and cardiologist Geoffrey Barnes, MD.

Over the course of the study, aspirin use among patients fell by 46.6%. With aspirin used less commonly, the risk of a bleeding complication dropped by 32.3% – equivalent to preventing one major bleeding event per every 1000 patients who stop taking aspirin.

“When we started this study, there was already an effort by doctors to reduce aspirin use, and our findings show that accelerating that reduction prevents serious bleeding complications which, in turn, can be lifesaving for patients,” said Dr Barnes. “It’s really important for physicians and health systems to be more cognisant about when patients on a blood thinner should and should not be using aspirin.”

Several studies had found concerning links between concurrent use of aspirin and different blood thinners, which prompted this aspirin de-escalation.

One study reported that patients taking warfarin and aspirin for AF and VTE experienced more major bleeding events and had more ER visits for bleeding than those taking warfarin alone. Similar results were seen for patients taking aspirin and direct oral anticoagulants – who were found more likely to have a bleeding event but not less likely to have a blood clot.

“While aspirin is an incredibly important medicine, it has a less widely used role than it did a decade ago,” Dr Barnes said. “But with each study, we are seeing that there are far fewer cases in which patients who are already on an anticoagulant are seeing benefit by adding aspirin on top of that treatment. The blood thinner they are taking is already providing some protection from clots forming.”

For some people, aspirin can be lifesaving. Many patients who have a history of ischaemic stroke, heart attack or a stent placed in the heart to improve blood flow — as well as those with a history of cardiovascular disease — benefit from the medication.

The challenge comes when some people take aspirin without a history of cardiovascular disease and are also prescribed an anticoagulant, said first author Jordan Schaefer, MD.

“Many of these people were likely taking aspirin for primary prevention of heart attack or stroke, which we now know is less effective than once believed, and no one took them off of it when they started warfarin,” Dr Schaefer said. “These findings show how important it is to only take aspirin under the direction of your doctor and not to start taking over-the-counter medicines like aspirin until you review with your care team if the expected benefit outweighs the risk.”

Source: Michigan Medicine – University of Michigan

Shift in Recommendations for Aspirin in CVD Prevention

Anatomical model of a human heart
Photo by Robina Weermeijer on Unsplash

The US Preventive Services Task Force (USPSTF) has issued a recommendation statement on the use of aspirin in the prevention of cardiovascular disease (CVD). The recommendation shifts the use of aspirin to an earlier window, and making it an individualised decision for people in their 40s to 50s with a > 10% 10-year CVD risk.

The previous recommendation from 2016 had called for low-dose aspirin for people in their 50s with a > 10% 10-year CVD risk and individualised decisions for those in their 60s with similar risk. The update comes after new evidence emerged in a number of randomised controlled trials.

For the update, which appears in JAMA Network, a systematic review was conducted on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD. The effect of aspirin use on colorectal cancer incidence and mortality was also investigated in primary CVD prevention populations, as well as the harms (particularly bleeding) associated with aspirin use.

The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults aged 40–59 years with a 10% or greater 10-year CVD risk has a small net benefit, and starting low-dose aspirin use for CVD prevention should be an individual decision for them. Those not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit. The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older.

Aspirin’s mechanism of action in CVD protection is well known. Aspirin at low doses is an irreversible cyclooxygenase 1 (COX-1) enzyme inhibitor, and at higher doses, it also inhibits COX-2. By inhibiting platelet function through COX-1, aspirin reduces atherothrombosis risk, and has been used widely for the prevention of CVD events, particularly for secondary prevention. However the COX-1 is also involved with protection of the gastrointestinal mucosa, and inhibition of it can promote gastrointestinal bleeding. The mechanism for the possible antineoplastic effects of aspirin is not as well understood.

Older age is one of the strongest risk factors for CVD, and men have a higher overall CVD disease burden and tend to experience CVD events earlier in life. Race and ethnicity affects CVD burden, with Black persons having the highest prevalence of CVD.

Similar CVD benefits appear for a low aspirin dose (≤ 100mg/d) and for all doses that have been studied in CVD prevention trials (50 to 500mg/d). A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the US.

Because CVD risk estimation is imprecise and imperfect at the individual level, the USPSTF suggests using these risk estimates as a starting point to discuss with appropriate candidates their desire for daily aspirin use. The benefits of initiating aspirin use are greater for individuals at higher risk for CVD events (eg, those with > 15% or > 20% 10-year CVD risk).

In addition to age and estimated level of CVD risk, decisions about initiating aspirin use should be based on shared decision-making between clinicians and patients about the potential benefits and harms, based on the relative values the patient places on these (reduced CVD risk vs increased bleeding and stroke risk).

Annual bleeding events in individuals without risk factors for increased bleeding (eg, history of gastrointestinal bleeding risk, history of peptic ulcer disease, or use of nonsteroidal anti-inflammatory drugs or corticosteroids) are rare, but risk for bleeding increases modestly with advancing age. For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. However, benefits shrink with advancing age because of increased bleeding risk, with modelling data suggesting stopping aspirin use around age 75.

Researchers Halt Aspirin Trial to Prevent Breast Cancer Recurrence

Source: National Cancer Institute

A large randomised trial was halted after preliminary analysis found that taking aspirin after treatment for breast cancer did not reduce the risk of disease recurrence.

Laboratory studies had previously shown that aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) reduced breast cancer growth and invasion. Non-steroidal anti-inflammatory drugs (NSAIDs) display anticancer activity through the inhibition of the COX-2 enzyme, triggering processes such as apoptosis, a reduction in proliferation and inhibition of carcinogenesis.  Several observational studies have shown a reduced risk of breast cancer mortality among regular aspirin users. 

There was a 25% higher risk of invasive recurrence in patients who took aspirin for a median of 18 months, but not statistically different from placebo (P = 0.1258). The aspirin group had an excess of all disease-related events, including death, local and distant recurrence/progression, and new primary tumours.

The results are in line with similar trials that ended while the Aspirin after Breast Cancer (ABC) trial was ongoing, Wendy Y. Chen, MD, of Dana-Farber Cancer Institute in Boston, said during a presentation at the American Society of Clinical Oncology (ASCO) Plenary Series.

“In this double-blind, placebo-controlled randomised trial, there was no benefit of aspirin 300 milligrams daily in terms of breast cancer invasive disease-free survival,” reported Dr Chen. “Although follow-up was short, the futility bound was clearly crossed. We had reached 50% of the events, and there was a numerically higher number of events in the aspirin arm. Therefore, it was unlikely that even with further follow-up there wouldn’t be any benefit associated with aspirin.”

“Although inflammation may still play a key role in cancer, it’s important to remember that aspirin may have different effects in other cancers, such as colon, or in different settings, such as primary versus secondary prevention,” she added.

Though the trial was well designed, enrolled the right population and with adequate dosing. the trial was stopped early for futility, commented Angela DeMichele, MD, of the Abramson Cancer Center at the University of Pennsylvania.

“The direction and magnitude [of the difference in events] highly preclude the possibility that there would have been a benefit with more follow-up,” said Dr DeMichele. “Although it was not statistically significant, we cannot rule out the possibility of a potential increase in breast cancer recurrence from the use of aspirin.”

“For patients and providers at this time, aspirin should not be used simply to prevent breast cancer recurrence,” she continued. “For those situations in which there are other options, decisions about aspirin use for other indications should definitely include an individualised risk/benefit discussion between physician and patient.”

The results underscore the need for prospective, randomised clinical trials to validate the effects of interventions from observational studies, she concluded.

The ABC trial involved patients under 70 with HER2-negative, high-risk breast cancer. The study randomised 3021 participants to 300 mg of aspirin daily or matching placebo for 5 years, with the primary endpoint being invasive disease-free survival. 

Dr Chen further noted that three clinical trials of aspirin or NSAID treatment ended while the ABC trial was ongoing. The Canadian-led MA.27 trial of an aromatase inhibitor plus celecoxib ended due to toxicity in the celecoxib arm. The randomised REACT trial of celecoxib in HER2-negative breast cancer showed no difference in disease-free survival after more than 6 years of follow-up.

The ASPREE trial tested low-dose aspirin on all-cause mortality in healthy older patients, and results showed a trend to increased all-cause mortality and significantly higher cancer mortality in the aspirin arm. 
During the post-presentation discussion, an audience member asked whether the results definitively ruled out a late benefit of aspirin, given that most patients had HR-positive disease wherein late relapse is not uncommon.

“It’s always frustrating when a study is closed early, and it was done in this case after we had reached 50% of the expected benefits,” said Chen. “There was an increase [in clinical events]. Not a statistically significant increase, but it was bordering on statistical significance. In order for aspirin to have a benefit, it would mean that in the second half, there would need to be a significantly decreased risk. It would basically need to flip and that would be biologically difficult to imagine.”

“I think it’s fair to say that this study doesn’t say definitively that there’s harm, but as for the likelihood of a benefit of aspirin, that would be extremely unlikely,” she said.

Source: MedPage Today

New Guidance Pivot on Daily Aspirin Advice

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In a distinct on previous advice, new draft recommendations posted by the U.S. Preventive Services Task Force (USPSTF) advise against adults 60 and older to begin taking aspirin to lower their risk of a first heart attack or stroke. 

They further advise that people aged 40 to 59 at higher risk for cardiovascular disease, but without a history of it, should talk to a health care provider before starting an aspirin regimen.

The proposed guidance is based on new evidence that suggests the potential harms of taking aspirin can outweigh the benefits. While daily aspirin use reduces the odds of a first heart attack or stroke, it increases the risks of gastrointestinal and intracerebral bleeding, which progressively increase with age.

“The latest evidence is clear: starting a daily aspirin regimen in people who are 60 or older to prevent a first heart attack or stroke is not recommended,” UPTSTF member Chien-Wen Tseng, MD, a professor at the University of Hawaii John A. Burns School of Medicine, said in a statement. “However, this Task Force recommendation is not for people already taking aspirin for a previous heart attack or stroke; they should continue to do so unless told otherwise by their clinician.”

The new guidance will be finalised after public comments close in November. It pivots from previous recommendations issued in 2016, which suggest that people ages 50 to 59 with a risk of cardiovascular disease ≥ 10% in the next decade and a low risk for bleeding take a daily low-dose aspirin (≤ 100mg/day) to reduce the likelihood of suffering a heart attack or stroke. According to the 2016 recommendations, the decision to start taking aspirin for preventive reasons should be “an individual one” for adults ages 60 to 69 who are at risk for cardiovascular disease

At present, neither the American Heart Association nor the American College of Cardiology recommend aspirin use for the prevention of heart attack and stroke in the general population; this only applies for some people between the ages of 40 and 70 who have never had a heart attack or stroke but have an increased risk for cardiovascular disease and a low risk for bleeding. The groups recommend that adults 70 and up should not take aspirin for first stroke or heart attack prevention.

Still, aspirin use for cardiovascular risk prevention is widespread in the US, “and is often self-initiated rather than recommended by a physician,” the latest USPSTF report states. A 2017 National Health Interview Survey (NHIS) found that 23.4 percent of adults age 40 or older and without cardiovascular disease took aspirin for primary prevention; among adults 60-69 years, 34.7 percent reported aspirin use.
Tomas Ayala, MD, a cardiologist at Mercy Personal Physicians, said that this pivot had been anticipated by doctors.

“It is not that aspirin is less effective at reducing heart attacks or strokes than it once was,” he told Health. “Rather, it is that we have other therapies at our disposal that have reduced the overall population risk of these conditions, so the relative benefit of aspirin is less, and in many cases, is outweighed by the risks.” 

Source: AARP

Aspirin Could Cut Cancer Deaths by 20%

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Patients with a wide range of cancers who take aspirin as part of their treatment could have their risk of death decrease by 20%, according to a major review of existing research.

Researchers at Cardiff University carried out a huge  systematic review of 118 published observational studies in patients with 18 different cancers. Pooling the results, 250 000 patients with cancer who reported taking aspirin, which was associated with a reduction of about 20% in cancer deaths.

The review said the available body of evidence regarding its efficacy and safety “justifies its use” as a supplementary treatment in a wide range of cancers—and that patients should be made aware of this.

Lead author Professor Peter Elwood, Honorary Professor at Cardiff University who has studied the effects of aspirin for over five decades, said: “In recent years, my research team and I have been struck by the actions of aspirin on the biological mechanisms relevant to cancer—and these seem to be the same in many different cancers.

“We therefore wanted to review the scientific evidence available on the use of aspirin as an additional treatment for a wide range of cancers.

“Overall, we found that at any time after a diagnosis of cancer, about 20% more of the patients who took aspirin were alive, compared with patients not taking aspirin.”

The team took into consideration aspirin taking risks and wrote to an author on each of the papers asking about any stomach or other bleeding episodes.

A minority of patients had experienced a bleed, but no evidence of any excess deaths attributable to bleeding in the patients on aspirin was found, the review noted.

“Our research suggests that not only does aspirin help to cut risk of death, but it has also been shown to reduce the spread of cancer within the body—so-called metastatic spread,” said Prof Elwood.

“There is now a considerable body of evidence to suggest a significant reduction in mortality in patients with cancer who take aspirin—and that benefit appears to not be restricted to one or a few cancers.

“Aspirin therefore appears to deserve serious consideration as an adjuvant treatment of cancer and patients with cancer and their carers should be informed of the available evidence.

“However, we must also stress that aspirin is not a possible alternative to any other treatment.”

It started in 1974 when a research team led by Professor Elwood and Professor Archie Cochrane at the Medical Research Council’s Unit in Wales showed for the first time that taking an aspirin tablet a day reduced deaths from heart disease and stroke by about 24%.

In 1990, the finding gained global traction and was judged by the BMJ to have been one of the top 50 most important research studies published since 1945. A meta-analysis of 13 randomised controlled studies found a major adverse cardiovascular event risk reduction for statin users (12%), non-smokers (10%) and males (11%).

Prof Elwood said his original study stimulated a new phase of research work on aspirin. At the time of the report about 100 clinical research studies on aspirin were published each year—but now, in excess of 1 000 are reported each year. He said a number of new clinical trials had been set up to test aspirin treatment in several cancers and the results of these should offer further clear evidence.

“Further research into aspirin and cancer would clearly be of great value, and new studies should be encouraged, especially if focused on some of the less common cancers,” said Prof Elwood.

Source: Medical Xpress

Journal information: Peter C Elwood et al, Aspirin and cancer survival: a systematic review and meta-analyses of 118 observational studies of aspirin and 18 cancers, ecancermedicalscience (2021). DOI: 10.3332/ecancer.2021.1258

Aspirin Plus Blood Thinners Isn’t Always Better

Collection of pills. Photo by Myriam Zilles on Unsplash

A new study has confirmed that combining two different blood thinners doesn’t necessarily improve outcomes. 

The new publication examined the minimal pros and the serious cons of combining a daily aspirin with a drug from the newer class of direct oral anticoagulants (DOACs) which include apixaban, dabigatran, edoxaban and rivaroxaban.

Patients were taking DOACs to prevent strokes from non-valvular atrial fibrillation or for the treatment of venous thromboembolic disease (deep vein thrombosis or pulmonary embolism). The included patients lacked another reason to take aspirin, such as a recent history of a heart attack or having had a heart valve replacement. One-third of those taking DOACs

“The patients on combination therapy were more likely to have bleeding events but they weren’t less likely to have a blood clot,” said lead author Jordan Schaefer, MD, an assistant professor of internal medicine and a haematologist at the University of Michigan. “Therefore, it’s important that patients ask their doctors if they should be taking aspirin when they are prescribed a direct oral anticoagulant.”

Combination therapy with an anticoagulant and an antiplatelet may be appropriate for people who have had a recent heart attack, recent coronary stent placement or bypass surgery, prior mechanical valve surgery or known peripheral artery disease, among other conditions, according to co-author Geoffrey Barnes, MD, MSc, an assistant professor of internal medicine and a vascular cardiologist at the Michigan Medicine Frankel Cardiovascular Center.

For the others, “combination therapy may not be happening intentionally; rather, the addition of aspirin might get overlooked because it’s not in any one specialist or general care provider’s territory,” Prof Barnes said.

There are many situations where an aspirin and DOAC combination has been insufficiently studied, and Prof Schaefer added that they are planning a larger, lengthier study since there were insufficient blood clots during the study to assess aspirin’s potential benefit.

Profs Schaefer and Barnes had also previously reported increased adverse outcomes for patients receiving both aspirin and warfarin, which is not a DOAC.

Source: Medical Xpress

Journal information: “Adverse Events Associated with the Addition of Aspirin to DOAC Therapy Without a Clear Indication,” JAMA Internal Medicine. DOI: 10.1001/jamainternmed.2021.1197