Don’t miss a new accredited #tweetorial launching TOMORROW here on @cardiomet_CE. #Interventional #cardiologist, #researcher, & #SoMe education leader @DLBHATTMD will be talking all about #aspirin, its role in #cardiovascular wellness & prevention, and new approaches to . . .
. . . formulation and dosing. Don't miss it--FOLLOW US NOW! @cpcannon @AnnMarieNavar @DrM_ODonoghue @DrMarthaGulati @practicalcardio @GuyattGH @DrMauricioCohen @SVRaoMD @ASPCardio @PlateletDoc @stephanamayer @CMichaelGibson @JJheart_doc @DrSheilaSahni @mmamas1973 @Drroxmehran
1) Welcome to an #accredited #tweetorial on the foundational role of #aspirin in #cardiovascular care. There are new approaches to #aspirin formulation & dosing. This program is accredited for 0.50h CE/#CME. I am @DLBHATTMD. #FOAMed #cardiotwitter #medtwitter 
2) This tweetorial is supported by an educational grant from PLx Pharma, and is intended for healthcare professionals. Faculty disclosures are listed at cardiometabolic-ce.com/disclosures/ and similar programs on #antiplatelets, still available for credit, are at cardiometabolic-ce.com/category/plate….
3) #Aspirin remains the most commonly used #cardiovascular drug worldwide. A major problem has been underutilization in appropriate pts, especially in secondary prevention. This was documented in the international REACH Registry & remains a problem. See jamanetwork.com/journals/jama/…
4) The goal of REACH was to categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of #atherothrombosis using simple clinical descriptors.
5) Across 4 yrs, among 45,227 patients with baseline data, total of 5,481 patients (12.1%) experienced at least 1 event (#cardiovascular death, #MI, #stroke). The 48.4% w/ a prior history of ischemic events at baseline had the highest rate of subsequent ischemic events (18.3%).
6) Patients with stable #coronary, #cerebrovascular, or #PAD peripheral artery disease (33.7%) had a lower risk (12.2%), and pts without established #atherothrombosis but with risk factors only (17.8%) had the lowest risk (9.1%; p < 0.001 for all comparisons).
7) In multivariable modeling, the presence of #diabetes (hazard ratio [HR], 1.44), an #ischemic event in the previous year (HR, 1.71), & #polyvascular disease (HR, 1.99) each were associated (all p < 0.001) with a significantly higher risk of the primary end point.
8) Aspirin and #statin use were both independently associated with a lower rate of CV death, MI, and stroke. From jamanetwork.com/journals/jama/…:
9) Randomized data support the observations from REACH about aspirin and statins. The REACH data help illustrate how simple therapeutic maneuvers such as aspirin and statin use can reduce CV events in real world practice. @gabrielsteg
10) While there has been some controversy about #aspirin in primary prevention based on conflicting trial data in different populations, for secondary prevention aspirin remains an important part of the core therapies.
11) Even in high-risk primary prevention, such as patients with #diabetes and other #cardiovascular risk factors but without elevated #bleeding risk, it remains a reasonable option to discuss with patients.
12) The ASCEND trial did in fact show a significant reduction in the primary endpoint with #aspirin vs placebo in #diabetes. See 🔓full text at nejm.org/doi/full/10.10….
13) Just published in the Journal of Diabetes and Its Complications, the DCRM Multispecialty Guidelines for Management of Diabetes provides guidance on this issue by Handlesman et al @yhandelsmanmd. Coming now to dcrmi.com/practice-recom….
14) Per that document, released at #WCIRDC2021 just last week, patients with two or more CV risk factors (for example, elevated LDL-C, diabetes, cigarette smoking, family history of CVD) may benefit from low dose aspirin if at low risk of bleeding.
15) So-called aspirin-free strategies have been put forth, and in certain contexts, such as patients with atrial fibrillation #Afib on therapeutic #anticoagulation, this makes sense. We'll explore that more tomorrow.
16) Meanwhile, let's see what you think. In a patient with #Afib and #CAD who undergoes #PCI, what is the recommended LONGEST duration of "triple" therapy (ASA+#P2Y12i+oral anticoagulant)?
17) Return tomorrow, check your answer, and keep learning & earning (CE/#CME, that is). @MedTweetorials @DLBHATTMD @cpcannon @gcfmd @hvanspall @DrMarthaGulati @mirvatalasnag @SABOURETCardio @ErinMichos @purviparwani @ajaykirtane @djc795 @mghmedres @Claudia_Editor @md_pollack
18) Welcome back! We are talking #ASA for #cardiovascular event risk reduction. This is your source for CE/#CME-accredited, serialized education on Twitter! I am @DLBHATTMD. @CardioNerds @radcliffeCARDIO @MGHCVFellows @a_l_bailey
19) Yesterday's poll? The answer is (b) one month, per the recent update, "Antithrombotic Therapy in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Undergoing Percutaneous Coronary Intervention: A North American Perspective."
20) Full text is at pubmed.ncbi.nlm.nih.gov/33555916/. Patients with #AFib and #CAD who then undergo #PCI are challenging for their optimal antithrombotic management because they require oral #anticoagulation for the prevention of cardiac thromboembolism . . .
21) . . . and dual antiplatelet therapy for the prevention of coronary thrombotic complications. BUT, the combination of oral anticoagulation and dual antiplatelet therapy substantially increases the risk of bleeding.
22) However, that one-month period of triple therapy is the longest; data from AUGUSTUS (@RenatoDLopes1 et al: 🔓nejm.org/doi/full/10.10…) suggest that longer than a week is rarely advisable.
23) When de-escalation of #DAPT is performed, typically #ASA should be dropped & the #P2Y12 inhibitor continued, typically clopidogrel in the context of afib. See again pubmed.ncbi.nlm.nih.gov/33555916/ for more detail.
24) The best-known de-escalation study to date (outside afib) is #TWILIGHT by @cardiomet_CE core faculty @Drroxmehran et al,🔓nejm.org/doi/full/10.10…
25) For the majority of patients with conditions such as acute coronary syndromes #ACS or recent #stenting, #aspirin remains an essential part of the therapeutic regimen. Who do the pertinent #guidelines say?
26) The primary prevention guidelines do allow use of #aspirin among select high #CV risk, low #bleeding risk patients (🔓pubmed.ncbi.nlm.nih.gov/30894318/)
27) In secondary prevention, the guidelines are very clear that barring an allergy, indefinite use is indicated. And aspirin remains an important part of both dual antiplatelet therapy and dual pathway inhibition (the #COMPASS regimen, see jacc.org/doi/10.1016/j.…).
28) So, there IS an enduring role for #aspirin in #cardiovascular #wellness & #prevention. But how much to give? There have been questions about the appropriate dose of chronic aspirin when used for cardiovascular purposes. See pubmed.ncbi.nlm.nih.gov/31196447/.
29) In the CURRENT OASIS-7 trial (free full-text at nejm.org/doi/10.1056/NE…), among 25,086 patients with #ACS, there was no significant difference between higher-dose (300-325mg daily) & lower-dose (75-100mg daily) #aspirin with respect to the primary outcome . . .
30) . . . of cardiovascular death, myocardial infarction, or stroke at 30 days (4.2% v 4.4%) or major #bleeding (2.3% v 2.3%). There was a significant⬆️in the incidence of minor bleeding among patients who received higher-dose aspirin (hazard ratio, 1.13; p=0.04).
31) There was also a small ⬆️in the incidence of major #gastrointestinal bleeding among patients who received higher-dose #aspirin, as compared with those who received lower-dose aspirin (0.4% v 0.2%, p=0.04). Six patients in each aspirin dose group had intracranial bleeding.
32) The more recent ADAPTABLE trial (full text free at nejm.org/doi/full/10.10…) did not find any major differences in efficacy or safety of 81 mg or 325 mg of #aspirin in terms of either #efficacy or #safety.
33) Based on OASIS-7 & several observational datasets (eg, acpjournals.org/doi/full/10.73…), it seems reasonable to use 75-100 mg (81 mg in the USA) daily when aspirin is being used for chronic cardiovascular purposes. When using less doesn't incur an efficacy cost, why not go there?!?
34) So now we turn attention to another area of uncertainty with respect to #aspirin: what is the optimal formulation? If you follow us here at @cardiomet_CE, you should have seen a recent #tweetorial from @CMichaelGibson on this subject. If not, check it out & get credit at ...
35) ... cardiometabolic-ce.com/plts10/. And let's see what you learned. The curves represent "standard" ASA, a new formulation called PL-ASA, and enteric-coated ASA. This study was done in obese diabetes patients, with dosing for 3 days. Which one do you think is ECASA?
Your answer to quiz (Tweet 35): VOTE NOW!!
38) Welcome back! We are talking #ASA for #cardiovascular event risk reduction & closing with new formulations. This is your source for CE/#CME-accredited, serialized education on Twitter! I am @DLBHATTMD. Yesterday's poll? That graph appeared (with the legend not hidden) ...
39) ... in pubmed.ncbi.nlm.nih.gov/28089180/. Absorption of PL-ASA (blue line) was 5X > ECASA (gray) (p<0.0001). Absorption of PL-ASA & "plain" ASA (black) overlap. For you #PK geeks, AUC of plasma concentrations after 325 mg dosing were: PL-ASA (2523), plain ASA (1964), ECASA (456).
40) Plain uncoated #aspirin is effective & cheap. However, concerns about dyspepsia as well as its impact on long-term adherence, & gastrointestinal ulceration & bleeding have persisted. Overall adherence to #ASA may be as low at 66% (pubmed.ncbi.nlm.nih.gov/26879354/).
41) The dyspepsia that aspirin can cause may decrease adherence, and one strategy that has been proposed is use of proton pump inhibitors #PPI, though that does mean an additional long-term medication (pubmed.ncbi.nlm.nih.gov/28363584/).
42) Enteric coated aspirin (#ECASA) may help dyspepsia in some patients, but no robust contemporary data prove any effect on gastrointestinal bleeding, despite that widespread assumption.
43) But several small older studies suggest that the enteric coating can⬇️absorption of aspirin and may therefore have less early #antiplatelet effect. The phospholipid coated aspirin (#PL-ASA) referenced above was found to result in more immediate #antiplatelet effect than ECASA
44) ASA complexed with phospholipids (PL-ASA) maintains gastric hydrophobicity; animal models suggest that in this case ASA exposure to GI lumen would be largely delayed until it exits the stomach. This ⬇️the risk of GI injury and, as seen above, preserves antiplatelet effect.
45) The clinical impact of those pharmacokinetic & pharmacodynamic observations is uncertain & requires testing in future randomized trials, but PL-coated aspirin was also compared with plain ASA & found to ⬇️short-term #GI ulceration on endoscopy (pubmed.ncbi.nlm.nih.gov/21081908/).
46) Future randomized trials will have to determine if this reduces clinical gastrointestinal bleeding. While a number of new approaches for #ASA formulations have been suggested (see @DLBHATTMD & @md_pollack (🔓10.1016/j.amjcard.2020.12.019) . . .
47) PL-ASA is a novel, already FDA-approved phospholipid-ASA formulation in a liquid-filled capsule that has been shown to be bioequivalent to plain ASA, yields faster & more complete absorption after a single 81mg dose & more predictable #antiplatelet effect compared to ECASA.
48) And that's it! You made it! Claim your 0.5h CE/#CME at cardiometabolic-ce.com/plts12/ now, & FOLLOW US for more accredited #tweetorials in #cardiometabolic medicine! Also JOIN US at @ckd_ce for more FREE credit focused on #CKD! Happy Holidays! I am @DLBHATTMD.
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