Aspirin: An oldie, but a goodie

Potential benefits include cancer prevention, cognitive protection, and reduced VTE risk

Aspirin has been around for decades, and its benefits for those with cardiovascular disease are well known. More recently, however, numerous publications have highlighted the benefits of aspirin for the prevention of cancer-associated morbidity and mortality, its positive effects on cognitive decline, and its use for preventing recurrent venous thromboembolism (VTE) and rates of major vascular events in those with a history of VTE. Pharmacists need to understand this emerging data on aspirin in order to counsel patients on this common OTC agent.

Cancer prevention

In three recent studies, two published in the April 28, 2012, issue of Lancet and one published in the May 2012 issue of Lancet Oncology, the use of aspirin resulted in significant reductions in the risk of cancer, metastasis, and cancer-related mortality. Overall, cancer mortality was 15% lower among regular aspirin users, metastases were 35% to 40% less common in those taking aspirin, and aspirin users had a 38% reduction in the risk of colorectal cancer compared with nonusers.

For cancer mortality, the investigators analyzed data from 34 trials involving 69,224 participants and found that aspirin use resulted in a 15% reduction in the risk for cancer deaths (P = 0.008), with the effect greatest after 5 years or more (P = 0.0005). In an additional analysis of data from six trials (n = 35,535) on low-dose aspirin for primary prevention, cancer incidence was 24% (P = 0.0003) lower with aspirin use after 3 years. The researchers also noted that aspirin use did not significantly increase the risk of major bleeding, with major extracranial bleeding actually occurring less often in those on low-dose aspirin versus controls.

For cancer metastases, researchers analyzed data from five large randomized trials involving 17,285 patients followed for a mean duration of 6.5 years. The investigators reported that randomization to aspirin was associated with a 36% reduction in the hazard ratio for cancer with distant metastasis (P = 0.001), including a 46% reduction in the hazard ratio for metastatic adenocarcinoma (P = 0.0007). They also noted that aspirin use reduced the risk of metastatic adenocarcinoma at diagnosis (31%, P = 0.02) and during subsequent follow-up periods (56%, P = 0.0009). The greatest benefits were observed for those with colorectal cancer who did not have metastatic disease at the time of diagnosis.

In the third analysis, researchers assessed data from 195 case–control and cohort studies to determine the association between aspirin use and risk of cancer; with results compared with recent reports of randomized trials. The investigators reported that use of aspirin was associated with a 38% risk reduction for colorectal cancer in the observational studies. They also observed similar consistent reductions for esophageal, gastric, biliary, and breast cancers, as well as when comparing data with randomized trial results. Use of aspirin was also associated with a 31% reduction in the proportion of cancers with distant metastasis.

In an accompanying editorial in the April 28 issue of Lancet, Andrew T. Chan, MD, and Nancy R. Cook, ScD, of Harvard and Brigham and Women’s Hospital in Boston, noted a number of limitations in these analyses. They pointe out that the analyses did not include data from the Women’s Health Study and the Physician’s Health Study, the largest randomized trials in primary prevention, which both showed that long-term use of alternative-day aspirin was not associated with a reduced risk of colorectal cancer. Chan and Cook also commented that since the trials included in the analyses evaluated cardiovascular outcomes, they may not have obtained information regarding cancer screening and surveillance.

Despite these caveats, Chan and Cook wrote, the analyses “show quite convincingly that aspirin seems to reduce cancer incidence and death across different subgroups and cancer sites, with an apparent delayed effect.” They go onto say, “For most individuals, the risk-benefit calculus of aspirin seems to favor aspirin’s long-term anticancer benefit.” They concluded, “Future evidence-based guidelines for aspirin prophylaxis can no longer consider the use of aspirin for the prevention of vascular disease in isolation from cancer prevention.”

Protecting cognition

Older women with high cardiovascular risk who used low-dose aspirin in a prospective, population-based cohort study experienced less decline on the Mini–Mental State Examination (MMSE) over a 5-year follow-up compared with those not on aspirin, according to research published in the October 3, 2012, issue of BMJ Open.

Researchers derived a sample of 681 women aged 70 years to 92 years without a diagnosis of dementia from the Swedish Population Register. The majority of these women had high cardiovascular risk, defined as 10% or higher 10-year risk of any cardiovascular disease event, according to Framingham criteria. The investigators treated 129 women with low-dose aspirin, while the remaining 552 did not receive aspirin. The women who received low-dose aspirin had smaller declines on MMSE over the 5-year follow-up period than nonusers (P = 0.004). The researchers did not, however, observe any difference between groups for short-term risk of dementia.

The authors commented that aspirin may influence cognitive decline by enhancing cerebral blood flow via a reduction in platelet aggregation. They also noted that aspirin may exert a neuroprotective effect via its ability to act through cyclooxygenase-2 to generate new neuroprotective docosanoids from docosahexaenoic acid and arachidonic acid. The researchers concluded that additional trials are needed, but for now, their data show that low-dose aspirin may have a neuroprotective effect in older women at high cardiovascular risk.

Benefits in those with VTE

Results from two trials published in the New England Journal of Medicine last year, in the May 24 and November 22 issues, showed that aspirin reduced the risk of VTE recurrence when given to patients with unprovoked VTE who had discontinued anticoagulation treatment, and that long-term aspirin use resulted in a significant reduction in the rate of major vascular events in a similar patient population.

Cecilia Becattini, MD, PhD, and colleagues conducted a multicenter, double-blind study to assess the clinical benefit of aspirin for the prevention of VTE recurrence after a course of treatment with a vitamin K antagonist in patients with unprovoked VTE. Patients with first-ever unprovoked VTE who had completed 6 months to 18 months of oral anticoagulant treatment were randomly assigned to aspirin 100 mg daily (n = 205) or placebo (n = 197) for 2 years, with the option of extending the study treatment.

During a median study period of 24.6 months, VTE recurred in 6.6% of patients who received aspirin and 11.2% of patients who received placebo (P = 0.02). Only one patient in each treatment group had a nonfatal major bleeding episode, and adverse events were similar between groups. The investigators concluded that low-dose aspirin is a potential alternative to extended oral anticoagulant treatment for long-term secondary prevention of VTE.

Timothy Brighton, MB, BS, and colleagues conducted a double-blind, placebo-controlled study to assess the use of low-dose aspirin (100 mg/d) in patients who had a first unprovoked VTE and who completed between 6 weeks and 24 months of initial anticoagulation therapy. A total of 822 patients were randomized to either low-dose aspirin (n = 411) or placebo (n = 411) and followed for a median duration of 37.2 months.

In contrast to the study results from Becattini and colleagues, these researchers found no significant difference in the rate of recurrent VTE in those assigned to aspirin or placebo (4.8% vs. 6.5%, P = 0.09). Use of aspirin reduced the rate of the two prespecified secondary composite outcomes, however. Low-dose aspirin reduced the rate of VTE, myocardial infarction, stroke, or cardiovascular death by 34% (P = 0.01) and the rate of VTE, myocardial infarction, stroke, major bleeding, or death from any cause by 33% (P = 0.01).

Brighton and colleagues also noted that the between-group differences were not significantly different for the rates of major or clinically relevant nonmajor bleeding episodes and serious adverse events. The investigators concluded that these results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy.

Implications for pharmacists

The decision to initiate aspirin in patients should be an individualized one, and health professionals should consider the benefits of therapy and potential risks. New data support the potential benefits of aspirin for cancer and recurrent VTE prevention or prevention of major vascular events in those with a history of VTE. In addition, data support the benefits of aspirin for the preservation of cognition in older women at high risk for cardiovascular events.

Educate patients inquiring about the use of aspirin for these effects on the quality of the current data, and tell them that additional well-designed trials may be needed to confirm some of these findings.