Use of Aspirin for primary prevention of cardiovascular disease - USPSTF guideline changes Pawan Hari MD MPH Director cardiac catheterization laboratory Dr. Hari indicated no potential conflict of interest to this presentation. He does not intend to discuss any unapproved/investigative use of a commercial product/device. Disclosures None
Aspirin Timeline 5th century BC Hippocrates 1897 AD Felix Hoffman/Friedrich Bayer 1900 present Most widely used drug in the world Physiology Irreversible cyclooxygenase (COX) inhibitor Preferentially blocks COX-1 activity at lower doses (75-100 mg/day) Decreases Thromboxane A2 activity. Prostacyclin I2 activity remains unimpeded. Decreases platelet activity and vasoconstriction COX-1 also produces multiple Prostacyclins required for maintenance of gastric mucosa. Aspirin therefore increases risk of GI bleeding
Guirguis-Blake et.al. Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113 Questions asked Does Aspirin use decrease the risk of MI, stroke, death from stroke or MI or all cause mortality? Does the effect vary by age, sex, race/ethnicity, smoking status, cardiovascular risk, DM or PAD? Does the effect vary by dose, formulation or duration of use? Does the use of Aspirin increase risk of GI hemorrhage or ICH? Guirguis-Blake et.al. Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113
Studies included in meta-analysis Results Nonfatal MI: 22% reduction (RR, 0.78 [95% CI, 0.71 to 0.87]; I 2 = 61.9%) Nonfatal stroke: No difference (RR, 0.95 [CI, 0.85 to 1.06]; I 2 = 25.1%) CVD mortality: No difference (RR, 0.94 [CI, 0.86 to 1.03]; I 2 = 8.8%) All-cause mortality: Little or no benefit (RR, 0.94 [CI, 0.89 to 0.99]; I 2 = 0%) Guirguis-Blake et.al. Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113
Effect Modification by Dose, Duration, and Formulation Similar reduction in non-fatal MI with low dose Aspirin Pooled analysis of trials using doses of 100 mg or less per day, showed a statistically significant reduction in nonfatal stroke (k = 7; RR, 0.86 [CI, 0.76 to 0.98]; I 2 = 0%) No effect on fatal MI or stroke, CVD mortality or all cause mortality Duration: Benefits begin within 1-5 years Formulation: No conclusions could be drawn Guirguis-Blake et.al. Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113 Differences in Subpopulations Age: Greater relative total MI benefit of aspirin in older age groups. Sex: No difference in outcomes by sex Diabetes: Available evidence does not clearly support the heterogeneity of aspirin's treatment effect based on diabetes status. Guirguis-Blake et.al. Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113
Effect of baseline risk on absolute risk reduction with Aspirin Guirguis-Blake et.al. Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113 Risk vs. Benefit
Risk of bleeding Whitlock et.al. Ann Intern Med. 2016 Jun 21;164(12):826-35. doi: 10.7326/M15-2112. Risk of bleeding by subgroups Whitlock et.al. Ann Intern Med. 2016 Jun 21;164(12):826-35. doi: 10.7326/M15-2112.
Factors that increase GI bleeding risk Patient has one of the following risk factors: History of ulcer disease, History of GI bleeding, Current dual antiplatelet therapy (Clopidogrel plus daily NSAID/aspirin) Current concomitant anticoagulant therapy (warfarin, enoxaparin, etc.) Patient has more than one of the following risk factors: 60 years or older, Systemic corticosteroid use Dyspepsia or GERD symptoms. Bhatt et.al. Circulation. 2008 Oct 28;118(18):1894-909. doi: 10.1161/CIRCULATIONAHA.108.191087. Risk factors for GI bleeding and ICH Concurrent anticoagulation or nonsteroidal anti-inflammatory drug (NSAID) use Uncontrolled hypertension Male sex Older age Bhatt et.al. Circulation. 2008 Oct 28;118(18):1894-909. doi: 10.1161/CIRCULATIONAHA.108.191087.
Other risk factors to consider Bleeding disorders, Renal failure Severe liver disease Thrombocytopenia. Bhatt et.al. Circulation. 2008 Oct 28;118(18):1894-909. doi: 10.1161/CIRCULATIONAHA.108.191087. Benefits of Aspirin Use Aspirin use moderately reduces risk for nonfatal MI and non-fatal stroke in adults aged 50 to 69 years who are at increased CVD risk. The magnitude of benefit varies by age and 10-year CVD risk. The USPSTF found adequate evidence that aspirin use reduces the incidence of CRC in adults after 5 to 10 years of use. Guirguis-Blake et.al. Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113
Net benefit of Aspirin in Men Guirguis-Blake et.al. Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113 Net benefit of Aspirin in Women Guirguis-Blake et.al. Ann Intern Med. 2016 Jun 21;164(12):804-13. doi: 10.7326/M15-2113
Length of therapy CVD prevention benefit begins within the first 5 years of use and continues as long as aspirin is used. The CRC prevention benefit is more complex. It takes at least 5 to 10 years of daily aspirin use to obtain a CRC benefit, the benefit may take 10 to 20 years to appear. Therefore, older adults and those with shorter remaining life expectancy may receive less benefit. Bleeding harms may occur in the short term. USPSTF conclusion The USPSTF concludes with moderate certainty that in the age group between 50 and 59 with a 10-year CVD risk of >=10%, the benefit of aspirin (CVD and CRC protection) outweighs risk (ICH and GIB) by a moderate amount. The USPSTF concludes with moderate certainty that in the age group between 60 and 69 with a 10-year CVD risk of >=10%, the benefit of aspirin (CVD and CRC protection) outweighs risk (ICH and GIB) by a small amount.
Clinical recommendation for age group 50-59 Initiate low-dose aspirin use for the primary prevention of CVD and CRC in this age group if following criteria are met: 10% or greater 10-year CVD risk, No increased risk for bleeding, Life expectancy of at least 10 years Willing to take aspirin daily for at least 10 years (Class B recommendation). Class B recommendation Clinical recommendation 60-69 years Decision to initiate Aspirin in this age group should be an individual one if following criteria are met: 10% or greater 10-year CVD risk. No increased risk for bleeding, life expectancy of at least 10 years, Willing to take low-dose aspirin daily for at least 10 years. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin. Class C recommendation
Caveats Evidence from primary prevention trials on the benefits of initiating aspirin use in adults younger than 50 years is limited. Adults younger than 50 years who have an increased 10-year CVD risk may gain significant benefit from aspirin use; how much benefit is uncertain. Evidence on the benefits and harms of initiating aspirin use in older adults is limited. Many adults aged 70 years or older are at increased risk for CVD because of their age. They have a high incidence of MI and stroke; thus, the potential benefit of aspirin could be substantial.
Decision making process The balance of benefits and harms of aspirin use is contingent on 4 main factors: Age Baseline CVD risk Risk for bleeding Preferences about taking aspirin