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Stopping Antiplatelet Therapy and Its Incidence of Cardiovascular Events

Patients who discontinue their daily aspirin for heart disease prevention may be at risk of further complications.

Aspirin is a common drug used for preventing secondary cardiovascular events in patients with history of thrombotic events such a stroke or myocardial infarction. Aspirin exert its effective anti-platelet properties in low doses when taken every day.  A clinician may consider discontinuing aspirin in some patients before surgery or they are at an elevated risk of bleeding; however, stopping therapy may put the patient at risk of thrombotic events as well, as it has been suggested by some studies. Long-term effects of aspirin discontinuation or poor compliance on patients with major cardiovascular risks have not been studied yet. Aspirin is also an over-the-counter drug, so previous studies have relied on self-reported data. In Sweden, however, a prescription is needed for a patient to purchase low-dose aspirin, which offers a more accurate data on adherence.

A cohort study was conducted in Sweden to investigate the associations of aspirin treatment persistence patterns and discontinuation with risk of cardiovascular events for patients taking aspirin for primary and secondary prevention. The investigators accessed the Nationwide Swedish prescribed drug register with the help of the Swedish National Board. A total of 601,527 long-term low dose aspirin users were included in the treatment persistence pattern analysis, 54% of them had a major cardiovascular event and 16% were classified as having been diagnosed with diabetes. They were all distributed in 4 time-updated aspirin persistence groups: 1. On aspirin: patients managing their diabetes with the nominal duration of aspirin dispensing; 2. Accumulation period: the time after the nominal therapy when the patient still has tablets left over; 3. Grace period: after the accumulation period, which corresponds to 80% adherence; 4. Off Aspirin: After the grace period with zero compliance inferred check-out records. The study was based on the On versus Off aspirin groups, but these two intermediate groups were used for transparency of the results. The primary outcome investigated was a first incidence of cardiovascular disease after the start of follow-up, defined as a hospitalization for myocardial infarction, stroke, or cardiovascular death.

Overall, patients who continued taking aspirin had the lowest incidence of cardiovascular events. Patients who had discontinued aspirin had a 37% higher rate of cardiovascular events, as defined by the primary outcomes. This corresponded to an absolute risk increase of 13.5 events per 1000 person-years at risk, meaning on average, 1 of every 74 patients who stopped the aspirin had an additional cardiovascular event in 1 year. Subgroup analyses further revealed that older patients and prior cardiovascular disease were at higher risk for cardiovascular events when off aspirin. However, patients who were also taking anticoagulant or another antiplatelet were found to have the lower risk of cardiovascular events when off aspirin.

Among the group of patients who used aspirin for secondary prevention, those who discontinued aspirin were associated with a 46% higher rate of cardiovascular events than those who were adherent, which was related to an absolute risk increase of 28.0 per 1000 person-years at risk.  Among the group of patients who probably used aspirin as part of primary prevention, discontinuing aspirin was associated with a 28% higher rate of cardiovascular events than continuing aspirin, an absolute risk increase of 6.9 per 1000 person-years at risk.

Aspirin discontinuation was also associated with nonfatal cardiovascular events, with a 10% higher risk of nonfatal cardiovascular events among people off versus on aspirin.

This was a major nationwide cohort study, which found that discontinuation of long-term low-dose aspirin was associated with a >30% higher risk of cardiovascular events. Aspirin discontinuation appeared even more dangerous among patients with history of cardiovascular disease and this risk did not appear to diminish over time. This study, however, did not find the relative risk of CV adverse events for patients who needed to stop aspirin temporarily, for example: when undergoing surgery. Some limitations of this study include lack of  socioeconomic status, physical examinations, including blood pressures, lipid panel or smoking status. Strengths include the large contemporary   sample rendering >60 000 cardiovascular events, universal coverage of the prescription register and inclusion of all long-term low-dose aspirin users nationwide, the nationwide coverage of registers for determining the outcomes, and minimal loss to follow-up.

Practice Pearls:

  • Discontinuation of long-term low-dose aspirin is associated with a higher risk of cardiovascular events.
  • The elderly and patients with prior history of MI or stroke have an even higher risk of cardiovascular events.
  • Upon discontinuation of aspirin, the risk of thrombotic events does not appear to diminish over time.

Reference:

Johan Sundstrom, MD, PhD, Jacob Hedberg, MD, PhD. Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events. Circulation. 2017 Sep 26;136(13):1183-1192

 

Fabio Rodriguez, PharmD. candidate 2018, LECOM School of Pharmacy