Douglas Corsi
@corsi_douglas
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#ACCMedStudent Journal Club @ACCinTouch
Philadelphia, PA
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1/13 Welcome to another installment of the
#ACCTweetorialSeries
covering key trials from
#ACCMedStudent
#JournalClub
! ⏰Today we'll be discussing the ADVOR trial on Acetazolamide for Acute Decompensated Heart Failure.🔎
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1/14 Welcome back to the
#ACCTweetorialSeries
! Today we'll review the ELAN trial on the timing of anticoagulation after acute ischemic stroke in patients with atrial fibrillation (AF).
#ACCMedStudent
#JournalClub
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1/14 Welcome back to the
#ACCTweetorialSeries
! Today we'll review the ISCHEMIA trial comparing an initial invasive vs conservative strategy in patients with stable coronary disease and moderate-severe ischemia.
#ACCMedStudent
#JournalClub
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1/14 Welcome to another installment of the
#ACCTweetorialSeries
covering key trials from
#ACCMedStudent
#JournalClub
! Today we'll discuss PARAGLIDE-HF on sacubitril/valsartan vs valsartan in heart failure with mildly reduced or preserved ejection fraction after a worsening event
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@AkivaRosenzveig
@AbdulkaderMoh99
@burke_khristian
@DianeMasket
@Lina_Ayasrah
@_MeghanaIyer
@pyrpyris
@Schroeder_luci
@sean_overy
@SebahatUlusan
@jolee_2022
Hope to have you join us for the next session!
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1/13 Welcome back to the
#ACCTweetorialSeries
covering topics presented in
#ACCMedStudent
#JournalClub
! Today, we'll be diving into the NOAH-AFNET 6 trial examining
#anticoagulation
for
#AHREs
detected by devices.
@pyrpyris
@Schroeder_luci
@sean_overy
@SebahatUlusan
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4/13 ADVOR, conducted at 27 sites in Belgium,
randomized 519 patients admitted for acute decompensated heart failure with signs of volume overload to receive either acetazolamide, 500mg IV daily, or placebo - in addition to protocol-driven IV loop diuretics.💊
@Lina_Ayasrah
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11/13 Limitations include conducting the study with a predominantly White population -which restricts generalizability, uncertain interaction with SGLT2 inhibitors, and the trial may have been underpowered to detect differences in clinical outcomes and adverse events.
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10/13 These findings support the consideration of acetazolamide as an adjunct diuretic therapy to enhance decongestion in acute HF patients with volume overload. Improving the efficiency of fluid removal may reduce HF hospitalizations and associated healthcare costs.💸
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10/14 In summary, ELAN suggests that early initiation of DOACs after acute ischemic stroke may be associated with a lower risk of recurrent stroke compared to later initiation without a significantly increased bleeding risk.
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9/13 ADVOR shows that adding acetazolamide to loop diuretics in acute decompensated HF with congestion can achieve faster and more complete decongestion without increasing adverse events, resulting in shorter hospital stays.🛌
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1/13 🎓Welcome to the ACC MSMC Tweetorial Series! We're excited to introduce this educational journey, where we will summarize pivotal clinical trials discussed with principal investigators at our
#ACCjournalclub
. Stay tuned for insights on the latest in cardiology
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7/13 Acetazolamide also shortened the median hospital stay by 1 day (8 vs 9 days, P=0.02) and increased the proportion of patients discharged without residual signs of volume overload (78.8% vs 62.5%, P<0.001) compared to placebo.
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13/13 Thanks for following along with this tweetorial on the ADVOR trial! Stay tuned for more
#ACCTweetorialSeries
covering the latest in CV research. Thanks to my fellow
#ACCMedStudent
#JournalClub
Members
@brhmrby
@Gamarra_NN
@TashaRWilson
@MarianaHenryL
@AdrianaCMares
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6/13 The primary endpoint, successful decongestion within 3 days, occurred in 42.2% of the acetazolamide group vs 30.5% of the placebo group (risk ratio 1.46; 95% CI 1.17-1.82; P<0.001). Acetazolamide led to greater fluid and sodium loss.❗
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3/13 Loop diuretics are the mainstay treatment for congestion in acute heart failure. However, their effectiveness can be limited by diuretic resistance. Acetazolamide, a carbonic anhydrase inhibitor, has been proposed as an adjunct therapy to enhance diuresis.❓
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2/13 ADVOR was a multicenter, double-blind, randomized, placebo-controlled trial that evaluated whether adding acetazolamide to loop diuretics could improve decongestion in patients hospitalized with acute decompensated heart failure and volume overload.🏥
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5/13 Key inclusion criteria were age ≥18 years, acute decompensated HF admission with ≥1 sign of volume overload (≥2+ edema, pleural effusion, ascites), elevated natriuretic peptides, and chronic oral loop diuretic use. Mean age was 78 years and 37% were women.
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13/14 In conclusion, PARAGLIDE-HF provides evidence for the potential benefits of sacubitril/valsartan over valsartan alone in heart failure with mildly reduced or preserved EF, especially after a recent worsening event.
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2/13 NOAH-AFNET 6 was a large randomized trial that compared edoxaban to placebo for
#stroke
prevention in older patients with subclinical atrial tachyarrhythmias.
@DianeMasket
@Gamarra_NN
@Lina_Ayasrah
@MarianaHenryL
@_MeghanaIyer
@jolee_2022
@AkivaRosenzveig
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8/13 There were no significant differences in the secondary endpoint of death or heart failure rehospitalization at 3 months. Rates of adverse events including hypotension, hypokalemia, and worsening renal function were also similar between groups.
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4/14 Patients were randomized 1:1 to sacubitril/valsartan titrated to 97/103 mg twice daily or valsartan 160 mg twice daily. The primary endpoint was time-averaged proportional change in NT-proBNP from baseline to Weeks 4 and 8.
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14/14 Thanks for following this
#ACCTweetorial
on the pivotal ISCHEMIA trial! Let us know your thoughts and insights on this practice-changing study.
#ACCMedStudent
#JournalClub
@brhmrby
@Gamarra_NN
@TashaRWilson
@MarianaHenryL
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11/14 These findings challenge the common practice of delaying anticoagulation for up to 2 weeks after a major stroke based on the 1-3-6-12 day rule. Earlier DOAC initiation may be reasonable in selected patients.
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8/14 The hierarchical composite outcome numerically favored sacubitril/valsartan but was not statistically significant (win ratio 1.19, 95% CI 0.93-1.52, p=0.16). There was a potential larger treatment effect in the EF ≤60% subgroup.
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5/14 Secondary endpoints included a hierarchical composite of CV death, HF hospitalizations, urgent HF visits, and change in NT-proBNP as well as recurrent CV events and worsening renal function.
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2/14 ELAN was an international, open-label RCT that enrolled 2014 patients (median age = 77 years, 45% female, median CHA2DS2-VASc = 5), with recent acute ischemic stroke and AF. Patients were randomized to early vs later initiation of direct oral anticoagulants (DOACs).
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10/14 In summary, sacubitril/valsartan led to greater NT-proBNP reduction and a potential clinical benefit vs valsartan in heart failure with mildly reduced or preserved EF after a worsening event, despite more hypotension.
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4/14 In the early group (n=1006), DOACs were started within 48 hours for minor/moderate strokes and on days 6-7 for major strokes. In the later group (n-=1007), DOACs were initiated on days 3-4, 6-7, and 12-14 for minor, moderate, and major strokes, respectively (1-3-6-12 rule).
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12/14 Limitations include the relatively small sample size, short follow-up duration, and lack of NT-proBNP data in 19% of patients. Only a few patients were on SGLT2 inhibitors, requiring further study of this combination.
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9/14 Rates of symptomatic hypotension were higher with sacubitril/valsartan (OR 1.73, 95% CI 1.09-2.76) but worsening renal function was lower (OR 0.61, 95% CI 0.40-0.93) compared to valsartan.
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14/14 Thanks for following this tweetorial on the practice-changing ELAN trial! Please respond with thoughts on how this trial affects practicing clinicians' decisions on when to initiate AC in patients with stroke and AF?
#ACCTweetorial
#StrokeNeurology
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11/14 These findings support considering sacubitril/valsartan in this population, particularly those with EF ≤60%, to enhance decongestion and potentially reduce HF hospitalizations after a worsening event.
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14/14 Thanks for following this
#ACCTweetorial
on the PARAGLIDE-HF trial! Let us know your thoughts and stay tuned for more updates from
#ACCMedStudent
#JournalClub
.
@brhmrby
@Gamarra_NN
@TashaRWilson
@MarianaHenryL
@AdrianaCMares
@AkivaRosenzveig
@AbdulkaderMoh99
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2/14 ISCHEMIA enrolled 5,179 patients with at least moderate ischemia on stress testing and randomized them to an initial invasive strategy of angiography and revascularization if feasible vs. an initial conservative strategy of medical therapy alone.
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3/14 Baseline characteristics: Median NIHSS score = 5 (IQR 2-11) at admission and 3 (IQR 1-6) at randomization. 38% in the early group and 37% in the later group had minor stroke; 40% and 39% had moderate stroke; 23% in each group had major stroke. ~50% were on aspirin at screen.
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6/14 For hierarchical composite analysis, win ratio is preferred as it prioritizes events based on their severity. Read more:
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7/14 The time-averaged reduction in NT-proBNP was greater with sacubitril/valsartan than valsartan (ratio of change 0.85, 95% CI 0.73-0.999, p=0.049).
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9/14 Rates of symptomatic intracranial hemorrhage were very low in both groups at 30 days (0.2% in each arm). There were also no significant differences in major extracranial bleeding or vascular death between groups.
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12/14 ISCHEMIA does not support routine invasive evaluation in all patients with stable CAD and moderate-severe ischemia, but an individualized approach is still warranted.
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13/13 We hope you enjoyed this
#ACCTweetorial
! Let us know your thoughts on key implications from the NOAH-AFNET 6 trial & future directions for the field. Thanks to my fellow tagged throughout!
#ACCMedStudentMembers
@AbdulkaderMoh99
@AdrianaCMares
@brhmrby
@burke_khristian
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3/14 The trial enrolled 466 patients stabilized after a worsening HF event. Mean age was 70 years, 52% women, median EF 55%. 33% had de novo HF and 69.5% were enrolled during the index hospitalization. Median NT-proBNP was 2009 pg/mL at screening.
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13/14 Nonetheless, ELAN provides important randomized data to help guide the timing of DOAC initiation after acute ischemic stroke. Shared decision-making is still needed based on individual bleeding and stroke recurrence risks.
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6/14 The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days.
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13/14 More research is still needed on optimal management of stable ischemic heart disease, including assessing quality of life and economic outcomes from ISCHEMIA.
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12/14 Limitations include the open-label design, relatively wide confidence intervals, and lack of data on functional outcomes or quality of life. The results provide an estimate of effect size but not definitive efficacy or safety conclusions.
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5/14 Infarct size was determined with standardized visual rating scheme: infarct < 1.5 cm = minor, infarct in cortical superficial branch of the MCA/ACA/PCA = moderate, and larger infarcts in the distribution of these arteries or brain-stem or cerebellar infarct > 1.5 cm = major.
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3/13 The trial enrolled 2536 patients ≥65yrs with ≥6min AHREs detected by cardiac devices and additional stroke risk factors. Patients had a median of 2.8 AHREs lasting 2.8 hours.
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2/14 PARAGLIDE-HF was a multicenter, double-blind, randomized trial that compared sacubitril/valsartan to valsartan alone in patients with ejection fraction >40% enrolled within 30 days of a worsening heart failure event requiring IV diuretics.
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3/14 Key exclusion criteria were an eGFR < 30 mL/min/1.73m2, a recent acute coronary syndrome, unprotected left main stenosis of at least 50%, LVEF < 35%, NYHA class III or IV heart failure, and unacceptable angina despite the use of medical therapy at maximum acceptable doses.
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8/14 Recurrent ischemic stroke at 30 days occurred in 1.4% with early DOAC vs 2.5% with later DOAC (OR 0.57, 95% CI 0.29-1.07). Results were similar at 90 days (1.9% vs 3.1%, OR 0.60, 95% CI 0.33-1.06).
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11/14 Limitations include lower-than-expected event rates, early stopping for futility, and potential offsetting effects of procedural vs spontaneous MIs impacting power.
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10/13 But more data is still needed on the best management of subclinical AF detected by devices before firm conclusions can be drawn.
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9/14 Results were insensitive to degree of ischemia or other baseline characteristics. No difference in primary outcome across subgroups including diabetes, angina, or CAD severity.
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5/13 Mean age was 78yrs, 37% female. Median CHA2DS2VASc score 4. ~20% developed diagnosed
#AF
during the trial. Median f/u 21m.
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11/13 Limitations include predominantly White European population, early termination, & groups not stratified by AHRE duration.
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7/13 ⭐️ So what did we find in the FIRE trial? A significant reduction in the primary composite endpoint of death, MI, stroke, or ischemia-driven revasc at 1 year. Specifically, 15.7% in the complete-revasc group vs. 21.0% in the culprit-only group, with a hazard ratio of 0.73.
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7/13 Stroke rate ~1%/yr in both groups - lower than predicted by risk scores. Suggests withholding anticoagulation in AHRE patients without diagnosed AF may be reasonable.
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6/13 Primary outcome (CV death, stroke, or systemic embolism): 3.2%/yr with edoxaban vs 4.0%/yr placebo (NS). More major bleeding with edoxaban.
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12/13 In summary, jury still out on
#anticoagulation
for
#AHREs
without diagnosed
#AF
. Weighing risks vs benefits is complex & more research is needed!
@TashaRWilson
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3/13 🚀 Launching into a deep dive on the Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) Trial. This study compared complete revascularization to culprit-only revascularization in patients aged 75 and above.
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7/14 Primary outcome events occurred in 2.9% with early DOAC vs 4.1% with later DOAC at 30 days (risk difference -1.18%, 95% CI -2.84 to 0.47). This suggests early DOAC may be safer, but the confidence interval includes the null.
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13/13 Stay tuned for more updates and thanks to my fellow
#ACCMedStudent
Members
#CardioTwitter
#FIREtrial
@_MeghanaIyer
@Lina_Ayasrah
@jannelalawrence
@DizzyToufik
@Andy35138551
@LukaMitar2
@jolee_2022
@AkivaRosenzveig
@OmneyaKandil
@farihahameed97
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9/13 Interpretation: NOAH-AFNET 6 does not clearly support starting
#anticoagulation
based purely on device-detected AHREs given ↑bleeding & no benefit.
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8/13 📉 This translates to a 27% lower relative risk of the primary composite outcome for those who underwent complete revascularization. These findings suggest that a more comprehensive treatment approach may be beneficial for older patients with MI and multivessel disease.
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10/14 In summary, routine invasive therapy did not reduce risk of ischemic events or death vs. initial conservative strategy over 3 years in patients with stable CAD and moderate-severe ischemia.
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4/13 The trial used a double-blind, double-dummy design. Patients were randomized 1:1 to edoxaban 60mg daily or placebo containing aspirin for some.
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8/13 However, the trial was underpowered due to early stoppage for futility & safety due to the increased risk of CV death and major bleeding with edoxaban.
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4/14 Enrolled patients had a median age of 64, 77.4% male, 66.3% White, 4.0% Black, 29.0% Asian, 15.8% Hispanic or Latino, 0.7% Other/multiple ethnic groups. 73.4% had HTN, 41.8% had diabetes, 4.0% had HF, and median Ejection Fraction was 60%.
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2/13 Remember to follow the series for post-journal club reports and expert discussions on groundbreaking trials. Let's dive into the evidence and learn together! 📈👨⚕️👩⚕️
#ACCTweetorials
#CardioEdRemember
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12/13 🎯 That's a wrap! The FIRE trial hints that complete revascularization could be a game-changer for older patients with MI and multivessel disease. But let's not get ahead of ourselves - we need more research to back this up and figure out the best strategy for each patient.
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8/14 Early hazard was higher with invasive strategy due to more procedural MIs, but late hazard was lower with fewer spontaneous MIs, suggesting potential offsetting effects over time.
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5/14 In the invasive group, 96% underwent angio and 79% had revascularization (74% PCI, 26% CABG). In the conservative group, 26% crossed over to angio and 21% had revascularization during follow-up.
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7/14 There was also no significant difference in the key secondary outcome of CV death or MI (14.2% vs 16.5% respectively, NS). Mortality was similar in both groups.
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9/13 📚 The FIRE trial adds to the evidence supporting the use of complete revascularization in patients with MI and multivessel disease. However, it's important to note that the trial's population was older (75 years and above), which is often underrepresented in such trials.
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6/14 Over median 3.2 year follow-up, the primary outcome of CV death, MI, or hospitalization for unstable angina/HF/arrest occurred in 16.4% with invasive strategy vs 18.2% with conservative strategy (Non-significant difference).
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5/13 📊 The trial was investigator-initiated, multicenter, prospective, superiority, open-label randomized. It included patients aged 75 and above admitted for Myocardial Infarction (MI) with multivessel disease.
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11/13 🛑 Limitations of the FIRE trial include its open-label design and the fact that it was conducted in only three countries (Italy, Spain, and Poland).
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10/13 🔄The results of the FIRE trial may change clinical practice by encouraging more complete revascularization in older patients with MI and multivessel disease. However, individual patient characteristics and preferences should always be considered.
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6/13 📝 1445 patients were randomly assigned to receive either physiology-guided complete revascularization (n=720) or culprit-only revascularization (n=725). The trial included patients with STEMI and NSTEMI. The median age was ~80 years, and 36.5% of the patients were female.
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4/13 How did we got here? Prior trials. COMPLETE showed benefits of complete revasc in younger patients. SWEDEHEART and PROSPECT highlighted issues with non-culprit lesions post-MI. FAME-2 showed advantages of FFR-guided revascularization in stable CAD
#Guidelines
#Trials
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