Aspirin for CV prevention—for which patients?

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Applied Evidence

Aspirin for CV prevention—for which patients?

J Fam Pract. 2011 September;60(9):518-523

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References

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In the ATT Collaboration¹⁸ analysis, the 5-year risk of bleeding with low-dose aspirin increased with the predicted 5-year CHD risk. Patients with the lowest CHD risk (<5%) demonstrated a 0.4% risk of bleeding vs 2.7% among patients having the highest CHD risk (>10%). However, the high-risk patients also had the largest benefit with low-dose aspirin therapy. According to the ATT Collaboration data, using aspirin alone vs placebo, the estimated number needed to treat (NNT) to prevent 1 serious vascular event (defined as vascular death, nonfatal MI, or stroke) was 50 patients for 5 years. When aspirin was added to other therapies such as statins, the NNT was 100 patients for 5 years. To cause 1 nonfatal extracranial bleeding event with aspirin in the same high-risk patients, the estimated number needed to harm (NNH) was also 100 patients for 5 years. A meta-analysis of 22 trials estimated a NNH to cause 1 additional major bleeding event with aspirin per year was 769 patients (95% CI, 500-1250).¹⁹

The Aspirin for Asymptomatic Atherosclerosis Trial (AAAT)²⁰ involved 3350 men and women ages 50 to 75 years with low ankle-brachial index and no history of CV disease (CVD). Participants were randomized to receive 100 mg enteric-coated aspirin or placebo daily and were followed for a mean of 8.2 years. The primary and secondary end points, which included fatal and nonfatal MI or stroke, were similar in the 2 groups, as were all-cause mortality and total adverse events. A difference in the incidence of major hemorrhage did not reach statistical significance—34 patients in the aspirin arm vs 20 in the placebo arm (hazard ratio [HR]=1.71; 95% CI, 0.99-2.97). One caution: the relative lack of benefit from aspirin reported in the AAAT may be due to the fact that it was powered to detect a 25% reduction in the event rate between groups, whereas the ATT Collaboration study¹⁸ found a 12% risk reduction in MI among those taking aspirin.

TABLE
Should you recommend aspirin? See how these patients “scored”*

Patient	Risk score	Prophylaxis
53-year-old woman, HTN on medication, SBP 152, nonsmoker, Chol 260, HDL 50	4%	No
48-year-old man, HTN on medication, SBP 138, nonsmoker, Chol 220, HDL 41	7%	No^†
68-year-old woman, HTN on medication, SBP 152, nonsmoker, Chol 260, HDL 50	11%	Yes
58-year-old man, HTN on medication, SBP 138, nonsmoker, Chol 220, HDL 41	14%	Yes
51-year-old man, HTN on medication, SBP 140, nonsmoker, Chol 180, HDL 41, Diabetes	6%	No^†
*Score for 10-year risk of CHD calculated with Framingham Heart Study data.¹⁴ ^†Under 2009 USPSTF recommendations, may consider aspirin therapy.¹⁰ Chol, total cholesterol; HDL, high-density lipoprotein; HTN, hypertension; SBP, systolic blood pressure.

Test for aspirin resistance? It’s still too soon
Patients receiving aspirin therapy may demonstrate residual platelet reactivity (laboratory resistance) or recurrent ischemic CV events (clinical resistance).²¹ Estimates of the prevalence of aspirin resistance vary widely.²² And available assays of residual platelet activity yield different results. Higher estimates of aspirin resistance may occur with assays that use an agonist other than arachidonic acid, such as collagen or adenosine diphosphate platelet aggregation, the whole blood platelet function analyzer (PFA-100), or urinary 11-dehydro-thromboxane B₂.²³

Several secondary prevention studies have demonstrated a positive association with laboratory resistance and adverse CV events, regardless of methods and assays used.²⁴ However, prospective primary prevention studies of this association are lacking. A meta-analysis of 20 clinical studies reported an increased risk of recurrent CV events including graft failure, acute coronary syndrome (ACS), and death among patients who exhibited aspirin resistance (odds ratio [OR]=3.85; 95% CI, 3.08-4.80). The authors identified a high level of heterogeneity among the studies, with 9 of the 20 failing to demonstrate an increased risk of events.²⁵

Using the PFA-100 assay, a prospective cohort study verified the presence or absence of aspirin resistance in 140 patients who presented to the emergency department with a non-ST–elevation ACS and who reported using aspirin daily for at least 7 days before the event.²⁶ Fifty-three patients (37.8%) were found to have aspirin resistance. Baseline characteristics of patients with and without aspirin resistance were similar except for an older age (mean 63.8 vs 58.3 years, respectively) and higher cardiac troponin values (mean 1.11 vs 0.41 ng/mL). Both groups were monitored for an average of 20 months; 45 patients with aspirin resistance and 79 without resistance completed follow-up. The presence of aspirin resistance increased the risk of MI (HR=3.02; 95% CI, 1.15-7.95) and decreased the risk of event-free survival (HR=2.46; 95% CI, 1.18-5.13). Adjusted for age, platelet count, cardiac troponin values, and coronary artery disease severity scores, the presence of aspirin resistance was associated with a 3-fold increased risk of CV events (HR=3.03; 95% CI, 1.06-8.62).