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Discontinuation of Low Dose Aspirin Can Lead To Risk Of Cardiovascular Events

Among long-term users, discontinuation of low-dose aspirin in absence of surgery or bleeding had a >30% increased risk of cardiovascular events.

Low-dose aspirin is recommended in guidelines and has strong evidence for secondary prevention of cardiovascular disease. In some studies, the discontinuation of aspirin has been associated with the higher risk of cardiovascular events.

In this cohort study from Circulation, 601,527 patients using low-dose aspirin as primary or secondary prevention in the Swedish prescription register from 2005 to 2009, were >40 years of age, free from previous cancer, and had greater than 80% adherence during the first observed year of treatment. The first three months after a major bleed or a surgical procedure were excluded from the time at risk.

To time the event of aspirin discontinuation, the researchers recorded the risk of cardiovascular events in relation to the time of aspirin discontinuation among patients that collected their prescription in a timely manner. They then compared patients who collected a timely fifth dispense with patients who did not pick up prescriptions after a series of 4 timely dispenses. The cardiovascular events were identified with the Swedish in-patient and cause-of-death registers. The outcome investigated was the first incidence of cardiovascular disease after the start of the follow-up, defined as a hospitalization for myocardial infarction, stroke, or cardiovascular death. Follow-up started after 1 year of aspirin treatment with high adherence. The patients were followed up until the first instance of the cardiovascular outcome, a new diagnosis of cancer, non-cardiovascular death, or the end of follow-up on December 31, 2009.

The timing of events after aspirin discontinuation analyses included 38,736 patients with 40,355 times at risk during which 216 cardiovascular events occurred. The patients who stopped aspirin treatment after 4 timely dispenses had an early risk increase for cardiovascular events compared to those who collected their fifth timely dispense.

The results found that aspirin discontinuation was associated with nonfatal cardiovascular events with a 10% higher risk of nonfatal cardiovascular events among people off as compared to on aspirin. The results showed that the discontinuation of long-term low-dose aspirin was associated with a >30% higher risk of cardiovascular events. The risk appeared to increase as soon as patients stopped aspirin, with no safe interval. Aspirin discontinuation seemed to be more precarious in patients with a previous cardiovascular disease with an additional cardiovascular event per year with 1 of every 36 secondary prevention patients with discontinued aspirin use as compared with an additional cardiovascular events per year in 1 of every 146 primary prevention patients that discontinued aspirin. Which means that there was an additional cardiovascular event observed per year in 1 of every 74 patients who discontinued aspirin. The patients on consistent aspirin treatment had the lowest incidence of cardiovascular events.

The limitations in this study were the risk of confounding in the observational studies. There was also a risk of reverse causation when patients about to die will stop taking aspirin and die anyway. The strength of this study was its large sample size of >60,000 cardiovascular events and use of universal coverage of the prescription register since aspirin is not available over the counter in Sweden. The study mentions that some experimental studies suggested that there is a rebound effect after aspirin discontinuation, which may result in increased thromboxane levels. The rebound effect may be important because of the large number of aspirin patients and high discontinuation rates. It’s also important to note that for patients who had planned surgery and discontinued aspirin for more than 7 days or more than 24 hours before the procedure it is unknown to be considered safe.

These findings support the use of aspirin as cardiovascular disease prevention and can have more influence for further measures of persistent use of aspirin in patients with risk of cardiovascular diseases.

Practice Pearls:

  • There is no safe window for aspirin discontinuation; risk of cardiovascular events increased immediately after discontinuation.
  • Patients who had consistent aspirin use had the lowest incidence of cardiovascular events.
  • Adherence to low-dose aspirin treatment is an important treatment goal for preventing cardiovascular events.

References:

Sundstrom, J, Hedberg, J, Thuresson, M, et al. Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study. Circulation 2017; 136:1183-1192.

 

Jessica Quach, Doctor of Pharmacy Candidate, Class of 2018, GA-PCOM School of Pharmacy