Aspirin’ to figure out if ASA can help prevent a heart attack? Interpreting all the new trials doesn’t have to cause chest pain! Join Dr. Ambarish Pandey from UT Southwestern as he helps The Curbsiders ASCEND the mountains of the latest studies to ARRIVE at some well-informed conclusions on the role of aspirin in primary prevention for cardiac events. The team also discusses secondary prevention, aspirin and dual (or triple) antiplatelet therapy, and whether it’s okay to stop giving aspirin to older adults without known CAD (Spoiler alert: it’s okay). ACP members can visit https://acponline.org/curbsiders to claim free CME-MOC credit for this episode and show notes (goes live 0900 EST).
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Written and produced by: Justin Berk MD, Matthew Watto MD
CME questions by: Justin Berk MD
Hosts: Matthew Watto MD, Paul Williams MD, Stuart Brigham MD
Edited by: Matthew Watto MD and Chris Chiu MD
Guest: Dr. Ambarish Pandey MD
The bleeding risk from aspirin (ASA) is likely worse than benefit of ASA in primary prevention of major adverse cardiac events “MACE” – (ARRIVE, ASCEND, ASPREE trials).
Aggressive reduction of other cardiac risk factors (eg BP control, smoking cessation) is more beneficial than aspirin therapy for primary prevention of MACE. (Ridker NEJM 2018)
Statin therapy has a much greater role than aspirin to prevent adverse cardiac events (Ridker NEJM 2018).
For elderly patients on long term aspirin for primary prevention, it is safe (and encouraged) to discontinue aspirin therapy. (ASPREE NEJM 2018)
Risk for recurrent cardiac events decreases as more times passes from an acute cardiac event (eg STEMI with stent placement). Keep this in mind when balancing bleeding risk with the long term use of antiplatelet agents and anticoagulants. -Dr Pandey’s expert opinion
NHANES data suggest a high percentage of patients are taking aspirin for primary prevention. This might make a nice article in SHM’s “Things we do for no reason” #twdfnr series. -Dr Watto’s non-expert opinion.
Aspirin – In-depth Show Notes
MACE: Major adverse cardiac event is usually defined as myocardial infarction (MI), stroke, or vascular death. Note #1: Detection of clinically insignificant, non-fatal MI is probably more common with higher sensitivity troponin testing. Note #2: MACE has different and stricter (less inclusive) definition than “clinical ASCVD” used in the 2018 AHA/ACC lipid guideline (see next).
Clinical ASCVD: The recently published 2018 AHA/ACC lipid guidelines define clinical atherosclerotic cardiovascular disease (ASCVD) as “acute coronary syndrome (ACS), those with history of myocardial infarction (MI), stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) including aortic aneurysm, all of atherosclerotic origin.” (Grundy et al. JACC 2018)
ASCVD Risk: Risk calculators like Framingham, the Pooled Cohort equations, or MESA typically, provide a 10 year risk estimate for ASCVD defined as “heart attack, stroke, stable angina, coronary revascularization, and peripheral arterial disease” –Ray et al. Eur Heart J 2014 .
*Note: Some sources define secondary prevention differently and consider patients with coronary or peripheral artery disease, and atrial fibrillation to be at high risk –Antithrombotic Trialists’ Collaboration – BMJ 2002 PMID: 11786451. We stick to the more simple definition of “Any patient with prior heart attack, or stroke”.
DAPT: Dual antiplatelet therapy = aspirin + another antiplatelet. Typically, clopidogrel, ticagrelor, prasugrel, etc.
Bleeding: Usually defined as intracranial bleeding, sight-threatening bleed of the eye, GI bleed or bleeding event resulting in hospitalization, transfusion, or fatality.
Number needed to treat (NNT): The number of patients that must receive the treatment in order to observe the benefit.
Number needed to harm (NNH): The number of patients that must receive the treatment in order to observe the harm.
DOAC / NOAC: Direct (Novel) Oral Anticoagulation (e.g. rivaroxaban)
Aspirin for Primary prevention
Does this patient have a history of MI or stroke?
This is a key decision point between primary or secondary prevention.
A patient with calcified coronary arteries seen on a CT chest is still categorized as primary prevention.
The term secondary prevention is used AFTER a cardiac event (see def. of MACE above) or revascularization e.g. percutaneous intervention (PCI), or coronary artery bypass graft (CABG).
Two large trials from the 1990s showed a beneficial effect for ASA in patients without prior MACE. Specifically, they found a decrease in MI (Physicians Health Study 2005) or stroke (Women’s Health Study 1989), but NOT mortality.
The event rates in these studies was much higher than that observed in the newer trials discussed below.
NEJM Editorial: Control of cardiac risk factors was different back then e.g. there was increased smoking in the original cohorts. Naturally, as risk factors decrease the absolute risk reduction from aspirin decreases. Consequently, the number-needed-to-treat to see a beneficial effect also increases.
Based on Physicians’ and Women’s Health studies and other similar studies: the USPSTF recommends using ASA for primary prevention in patients with a 10 year Framingham risk score of 10% or higher at age 50 – 60 years. Dr. Pandey notes that ASA’s bleeding risk is often in excess of its benefit. Thus, he recommends starting a statin before ASA because of better evidence, less bleeding risk, and fewer side effects.
(In fact, “nocebo effect” can partially explain statin-induced myalgia.)
Note: ASA use in a patient with known, but asymptomatic CAD seen on imaging (no history of MACE), is STILL considered primary prevention.
Additionally, ASA use in a patient with chronic stable angina and no history of MACE is STILL consider primary prevention.
A coronary artery calcium (CAC) score, can be used to calculate ASCVD risk with the MESA calculator (BUT n.b. this calculator is designed for for statin eligibility, NOT to decide who needs aspirin).
Dr. Pandey’s expert opinion: Aggressive risk factor modification is better than aspirin for primary prevention e.g. Exercise, diet, new diabetes medications (SGLT2 inhibitors or GLP-1 agonists), and statin treatment would all be better than aspirin.
If a patient has had coronary or peripheral revascularization (stent or arterial bypass), MI or stroke, then ASA use is considered secondary prevention.
Note: Some sources like 2018 AHA/ACC Lipid Guideline, 2002 Anti-thrombotic Trialists Collaboration use a broader definition of secondary prevention e.g. include stable angina and peripheral artery disease.
Case 1 – PCI for stable CAD
If a patient without prior MACE undergoes percutaneous intervention (PCI) with stenting for stable coronary artery disease (CAD), then continue DAPT for 6 months. Consider stopping clopidogrel (or other P2Y12 inhibitors) after this initial 6 months. Aspirin should be continued lifelong as monotherapy. -Dr Pandey’s expert opinion
Case 2 – PCI for Acute coronary syndrome (e.g. acute STEMI)
Continue DAPT (i.e. ASA plus clopidogrel) for one year. Then, calculate a DAPT score (from DAPT study). If the DAPT score is 2 or higher and no bleeding stigmata, then continue DAPT for 30 months before stepping down to aspirin monotherapy -Dr Pandey’s expert recommendation.
Note: You need the stent diameter to calculate a DAPT score.
Antiplatelet and anticoagulant coprescription
These include the DOACs, warfarin, low molecular weight heparin, fondaparinux, etc. We will use DOACs to highlight case examples below, but the rules would be the same for other anticoagulants coprescribed with aspirin.
Case 1 – Patient on ASA for secondary prevention without prior PCI/stent, but now needs long-term anticoagulation (e.g. DOAC)
Note: This group is not well studied and the above recommendation is expert opinion.
Shout out: Sparctool.com: Allows input of the CHA2DS2-VASc and HAS-BLED scores to visually compares medications, calculated benefit and bleeding risk. It’s awesome!
Case 2 – Patient on DAPT after PCI/stent, but now needs long-term anticoagulation (e.g. DOAC)
Dr Pandey recommends: Stop aspirin. Continue DOAC plus clopidogrel for 6-30 months based on patient’s indications for stenting and DAPT score (see ASA for secondary prevention above). Dr Pandey stops clopidogrel after the initial 6-30 months and continues DOAC as monotherapy to balance benefits with risk of bleeding.
In >2,000 patients with atrial fibrillation who underwent PCI/stenting, rivaroxaban 15 mg plus clopidogrel or rivaroxaban 2.5 mg twice daily plus DAPT had lower bleeding rates compared to “triple therapy” (warfarin plus DAPT) at 12 months without an increased rate of MACE.
In >2000 patients with atrial fibrillation who underwent PCI, the risk of bleeding was lower among those who received “dual therapy” with dabigatran and a P2Y inhibitor than among those who received “triple therapy” with warfarin plus DAPT. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events.
Great prescribing algorithm! I must admit I've never had a great rationale for who gets a daily aspirin.
Thanks for breaking this down for me.
Of course! Thank you for listening!