ISAR-REACT 5: Ticagrelor vs prasugrel in ACS

Schupke S, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. NEJM 2019

Bottom line: In patients with ACS planned for invasive management (90% treated with new-gen drug-eluting stent), prasugrel reduced death/MI/stroke versus ticagrelor (NNT=42) at 1 year, which was driven by fewer MIs.

Patients (n=4018 randomized)

  • Enrolled from 21 centres in Germany & 2 centres in Italy

  • Included if:

    • Hospitalized for ACS (STEMI, NSTEMI or unstable angina)

    • Planned invasive strategy (i.e. scheduled for coronary angiogram)

  • Key exclusion criteria:

    • Hx of any stroke, TIA or intracranial hemorrhage

    • Intracranial abnormality at risk of bleeding

    • Lysis <24h before randomization

    • Ticagrelor or prasugrel <5 days before randomization

  • Average baseline characteristics

    • Age 65 y, female 24%

    • Diagnosis @ admission: STEMI 41%, NSTEMI 46%, UA 13%

    • Final diagnosis of ACS at discharge 91%

    • Index ACS managed with: PCI 84% (90% of which were drug-eluting stents), CABG 2%, medical management only 14%

    • Prior MI 16%, prior PCI 23%, prior CABG 6%

    • Cardiac risk factors: HTN 70%, diabetes 22%, dyslipidemia 58%

    • BMI 28, wt <60 kg 5%

Interventions: Ticagrelor ASAP vs Prasugrel x1 year

  • Ticagrelor: Loading dose of 180 mg x1 ASAP after randomization (i.e. pre-loading before coronary angiogram), then 90 mg PO BID

  • Prasugrel: Loading dose of 60 mg x1, then 10 mg once daily

    • If STEMI: Loading dose given ASAP after randomization

    • If NSTEMI/UA: Loading dose given after coronary angiogram

    • Lower maintenance dose of 5 mg daily given if age age 75+ or weight <60 kg

  • ~20% in both groups were not discharged on their assigned study P2Y12i (most because they were not confirmed to have obstructive CAD on angiography, had indication for oral anticoagulant, or underwent CABG)

  • Note: Patients did not get the medication for free as part of the trial; they had to obtain it as they otherwise would need to do in standard practice

Outcomes @ 1 year

  • Primary outcome (composite of all-cause death, MI, stroke): Ticagrelor 9.3% vs prasugrel 6.9%

    • Hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.09-1.70

    • NNT (using prasugrel instead of ticagrelor)=42 @ 1 year

  • Secondary outcomes

    • Death: 4.5% vs 3.7% (HR 1.23, 95% CI 0.91-1.68)

    • CV death: 3.2% vs 3.0%

    • MI: 4.8% vs 3.0% (HR 1.63, 1.18-2.25), NNT=56 in favor of prasugrel

    • Definite/probable stent thrombosis: 1.3% vs 1.0%

    • Stroke: 1.1% vs 1.0%

    • Major bleed (BARC 3, 4 or 5): 5.4% vs 4.8% (HR 1.12, 0.83-1.51)

  • Discontinued study intervention: Ticagrelor 15.2% vs prasugrel 12.5%

    • Median time to D/C: 84 vs 109 days

Risk of bias: Overall some concern

  • Some concerns re: bias arising from the randomization process (allocation bias)

    • Computer-generated random sequence

    • Allocation concealment only by sealed, opaque envelopes (no details on storage location, sequential numbering or assignment); prone to tampering & less robust than other methods

  • Some concerns re: bias due to deviations from intended interventions

    • Open-label design

    • Higher & earlier discontinuation of study drug in ticagrelor group, though no other evidence of differences in management between groups

    • Predicted direction of bias in favor of prasugrel for the primary efficacy outcome

  • Low risk of bias due to missing outcome data (attrition bias)

    • Low loss-to-follow-up: <1% in both groups

    • Analyzed the intention-to-treat population

  • Low risk of bias in measurement of the outcome (detection bias)

    • Open-label design; however objective outcome definition (especially for MI, the driver of the difference between ticagrelor & prasugrel), & outcomes adjudicators not aware of assigned intervention

  • Low risk of bias in selection of the reported result (outcome reporting bias)

Other considerations

  • The findings of this trial conflict with results of prior trials of prasugrel & ticagrelor:

    • The results of the primary outcome of ISAR-REACT 5 expressed as prasugrel vs ticagrelor are 6.9% vs 9.3%, HR 0.74 (0.59-0.92)

    • In the PLATO trial comparing ticagrelor to clopidogrel in ACS patients managed medically or with PCI, ticagrelor reduced death/MI/stroke vs clopidogrel.

      • 10.2% vs 12.3%, HR 0.84 (0.77-0.92)

      • Notably, ticagrelor also reduced death vs clopidogrel (HR 0.78)

    • Similarly, in the TRITON-TIMI 38 trial comparing prasugrel to clopidogrel in ACS patients managed almost exclusively with PCI, prasugrel reduced death/MI/stroke vs clopidogrel @ 15 months

      • 10.7% vs 12.7%, HR 0.83 (0.75-0.92)

      • Prasugrel did not reduce death vs clopidogrel (HR 0.96)

    • Conversely, in TRILOGY, in which only medically-managed ACS patients were randomized, prasugrel did not reduce CV death/MI/stroke vs clopidogrel, HR 0.96 (0.86-1.07)

    • Note: The previous PRAGUE-18 trial (n=1230) that also compared prasugrel to ticagrelor was severely underpowered & inconclusive.

  • In terms of pharmacodynamics, ticagrelor inhibits platelet function at least as well as prasugrel, irrespective of assay technique (e.g. Rollini et al., SWAP-2, SWAP-3).

  • Adherence to the P2Y12 inhibitor was apparently assessed (as briefly described in the protocol), but not reported in sufficient detail in this article. Of patients who discontinued the study P2Y12 inhibitor, those in the ticagrelor discontinued approximately 1 month earlier than prasugrel, which may explain at least in part the early higher MI rate with ticagrelor vs prasugrel.

  • Overall, it’s unclear how much the findings of this trial are attributable to:

    • A yet-unidentified pharmacodynamic benefit of prasugrel;

    • Lower adherence to ticagrelor due to BID dosing;

    • Greater & earlier discontinuation of ticagrelor due to dyspnea.

  • Arguably, it’s also unclear how the efficacy of prasugrel compares to clopidogrel in the era of modern drug-eluting stents with incredibly low rates of stent thrombosis, and in this emerging era of complete revascularization.

IV iron in HFrEF with iron deficiency

Zhou X, et al. Iron supplementation improves cardiovascular outcomes in patients with heart failure. Am J Med 2019 [epub].

Bottom line: In patients with HFrEF who have iron deficiency, IV iron therapy:

  • has no clear effect on all-cause or CV mortality;

  • reduces the risk of HF hospitalizations (NNT 10 at 6-12 months);

  • improves quality of life (~4-point improvement on 100-point scale), functional capacity, & walking distance.

  • Current evidence does not suggest that oral iron supplementation offers any benefit.


  • In patients with heart failure with reduced ejection fraction (HFrEF), iron deficiency is defined as having a serum ferritin <100 ug/L OR ferritin 100-300 ug/L pls transferrin saturation (tsat) <20%

  • In HFrEF, iron deficiency is:

    • Present in 2/3 of patients with anemia & 1/2 of patients without anemia;

    • Associated with higher NYHA class (i.e. worse symptom burden), higher serum NT-proBNP, & higher risk of death (independent of hemoglobin concentration).

  • In the IRONOUT HF trial, oral iron supplementation (using Feramax 150 mg BID x4 months) in patients with HFrEF + iron deficiency did not improve quality of life or exercise capacity;

    • Importantly, 4-months of oral supplementation only modestly improved tsat (+3%) & non-significantly increased ferritin (+11 ug/L, 95% confidence interval [CI] -0.3 to +23), suggesting that this does not efficiently replace iron stores;

    • It remains unknown if other PO iron formulations, such as sulfate or fumarate salts, may be effective in these patients;

    • Also unknown whether PO iron could adequately maintain iron stores in patients first treated with IV iron.

  • 3 prior meta-analyses (Can J Cardiol 2016, Eur J Heart Fail 2016, Eur J Heart Fail 2018) all demonstrated a reduction in HF hospitalizations with intravenous iron (number needed to treat [NNT] over 6-12 months of 10-12); however, these studies were limited by restrictive eligibility criteria that included only 4-5 of the ~10 randomized controlled trials (RCTs).


  • Search timeframe: Database inception to March 2018

  • Databases searched: PubMed, Embase, CENTRAL

  • Additional measures: None

  • Eligibility criteria:

    • Published in English

    • Design: Randomized controlled trial (RCT), at least single-blind

    • Population: “systolic” HF (i.e. HFrEF)

    • Intervention: Iron supplementation

  • 10 trials identified (including the 2 largest trials, FAIR-HF & CONFIRM-HF)

  • Risk of bias: Variable, 2 largest IV iron trials (FAIR-HF & CONFIRM-HF) rated as being at overall low risk of bias

Patients (n=1404)

  • Inclusion criteria of FAIR-HF & CONFIRM-HF, the 2 largest trials:

    • HF with LVEF ≤45%

    • NYHA 2-3

    • Hb 95-135 g/L in FAIR-HF, <150 g/L in CONFIRM-HF

    • Iron deficiency (ferritin <100 ug/L or 100-300 ug/L plus tsat <20%)

  • Baseline characteristics in FAIR-HF:

    • Age 67, female 55%

    • Ischemic cardiomyopathy ~80%, prior MI ~58%

    • NYHA 2 (19%) or 3 (81%); 6-minute walk test (6MWT) distance 270 m

    • LVEF ~33%

    • Hb 119 g/L, MCV 92 um^3, ferritin ~60 ug/L, tsat ~17%

    • eGFR 65 mL/min/1.73 m^2

    • Meds: ACEI/ARB >90%, beta-blocker ~85%, MRA ?, digoxin ~15%

  • Baseline characteristics in CONFIRM-HF:

    • Age 69, female 45-50%

    • Ischemic cardiomyopathy 83%, prior MI 60%

    • NYHA 2 (~55%) or 3 (~45%); 6MWT distance ~290 metres

    • LVEF ~37%

    • Hb 124 g/L, ferritin 57 ug/L, tsat 18-20%

    • eGFR ~65 mL/min/1.73 m^2

    • Meds: ACEI 77%, ARB 23%, beta-blocker ~90%, MRA ?, digoxin 19-27%


  • Intervention: Iron

    • IV iron in 8 studies, with variable doses

      • e.g. mean 1850 mg given over 24 weeks in FAIR-HF, mean 1500 mg given over 1 year in CONFIRM-HF

    • PO iron in 3 studies, 200-600 mg/d

  • Control: Matching placebo infusion

Results @ ~6-12 months (range 2 weeks to 1 year)

  • Mortality (6 trials): Iron 3.3% vs control 4.6%; odds ratio (OR) 0.76, 95% CI 0.43-1.37

  • HF hospitalizations: (5 trials, all IV iron): 5.3% vs 14.5%; OR 0.39, 95% CI 0.19-0.80 (NNT 11)

  • Quality of life (4 trials; measured with Kansas City Cardiomyopathy Questionnaire [KCCQ]): 4.1 points better with iron than control

    • KCCQ range 0-100; 5-point change considered minimally clinically important difference (MCID)

    • Note: Mean improvement over placebo of 4.4 (CONFIRM-HF), 6.6 (FAIR-HF), & 7.6 in 3 trials of IV iron vs placebo; mean improvement 0.1 in 1 trial of PO iron vs placebo (the aforementioned neutral IRONOUT HF trial)

    • Other QoL scales: EQ-5D (2 trials; 4 points better with IV iron), MLHFQ (2 trials; 19 points better with IV iron)

  • NYHA functional class (5 trials): -0.7 (better) with IV iron vs control

  • 6MWT (5 trials): Distance 33 m farther with IV iron vs control

  • LVEF (3 trials): 3.8% higher with IV iron vs control

Ongoing areas of uncertainty:

  • What is the long-term efficacy & safety of IV iron therapy for HFrEF? Does IV iron therapy reduce the risk of death in patients with HFrEF? (ongoing trials: FAIR-HF2, HEART-FID, IRONMAN)

  • Can IV iron therapy reduce the risk of recurrent HF hospitalizations among patients admitted for acute HF? (ongoing trial: AFFIRM-AHF)

  • Would a different PO iron formulation be effective for iron replacement in patients with HFrEF? (ongoing trial: NCT03344523)

  • What is the optimal duration, route & maintenance regimen for iron therapy following IV iron replacement?

  • Is IV iron beneficial in patients with HF with LVEF >45%? (ongoing trials to assess this: FAIR-HFpEF)

AUGUSTUS - Antithrombotic regimens including apixaban vs warfarin, & aspirin vs placebo, in patients with AFib plus PCI &/or ACS

Reference: Lopes RD, et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. NEJM 2019.

Bottom line: In patients with atrial fibrillation who either undergo PCI and/or have ACS, in combination with a P2Y12 inhibitor (almost always clopidogrel):

  • Apixaban reduces the risk of major or clinically-relevant non-major bleeding (NNT=24), hospitalizations (NNT=27), & stroke (NNT=84) compared to warfarin at 6 months;

  • Aspirin (beyond the first week) increases the risk major or clinically-relevant non-major bleeding (NNH=15), without a clear effect on hospitalization/death or ischemic events compared to placebo at 6 months;

  • Therefore, an antithrombotic regimen of apixaban + clopidogrel (without aspirin) should be routinely considered in these patients. Warfarin should be limited to patients for whom a DOAC is contraindicated, intolerable or unaffordable; & aspirin beyond the first week should be limited to patients with very high risk of stent thrombosis/recurrent coronary events.

Patients (n=4614 from 33 countries)

  • Included if (all of the following):

    • Age 18+ years

    • Known AF (paroxysmal, persistent or permanent) with planned long-term oral anticoagulation

    • Recent (<14 days) ACS &/or PCI with plan for 6+ months of P2Y12 inhibitor

  • Key exclusion criteria:

    • Other indication for anticoagulation (prosthetic valve, VTE, mitral stenosis, etc)

    • History of intracranial hemorrhage, ongoing bleeding or coagulopathy

    • Recent/planned CABG

    • “Severe” renal insufficiency

  • Average baseline characteristics:

    • Age 71 years, male (71%), white (92%)

    • Qualifying event: ACS+PCI (37%), medically-managed ACS (24%), elective PCI (39%)

      • ~6.6 days from ACS/PCI to randomization

    • CHA2DS2-VASc ~4, HAS-BLED ~3

    • Prior stroke/TIA/thromboembolism (14%), HF (43%), HTN (88%), diabetes (36%)

    • SCr >133 (8%)

    • Previous oral anticoagulant (49%)

Interventions x6 months

  • 2x2 factorial design: Patients were simultaneously randomized to apixaban vs warfarin & aspirin vs placebo within 14 days of ACS &/or PCI, so total of 4 different intervention groups.

  • Management prior to randomization: At the discretion of treating physicians according to local standard of care (likely that all at least received DAPT +/- anticoagulation leading up to randomization, though not recorded/reported)

  • Anticoagulation: Apixaban vs warfarin

    • Apixaban arm: 5 mg PO BID

      • Reduced to 2.5 mg PO BID if 2 of the following: Age >80 years, wt <60 kg, SCr >133 umol/L

      • Discontinued study regimen prematurely: 13%

    • Warfarin to target INR 2.0-3.0

      • Median time in therapeutic range (TTR)=59%; INR<2.0 23% of the time, INR>3.0 3% of the time

      • Discontinued study regimen prematurely: 14%

  • Antiplatelet: Aspirin 81 mg PO daily vs matching placebo

    • Discontinued study drug prematurely: 15-17%

  • All: P2Y12 inhibitor left at the discretion of the treating clinicians (clopidogrel 93%, prasugrel 1%, ticagrelor 6%)

  • After 6 months, anticoagulation & antiplatelets were managed according to local standard of care (i.e. not standardized for the trial)

Results @ 6 months

  • Primary outcome: Major or clinically-relevant non-major bleeding, ISTH definition

  • Key secondary outcomes: Composite of death or hospitalization; composite of death or ischemic events (stroke, MI, definite/probable stent thrombosis, or urgent revascularization).

Outcomes at 6 months of apixaban versus warfarin in combination with P2Y12 inhibitor +/- aspirin

Outcomes at 6 months of aspirin versus placebo in combination with P2Y12 inhibitor + apixaban or warfarin

Risk of bias

  • Low risk of: Allocation bias (allocation concealed via interactive voice-response system), attrition bias (low [0.3%] loss to follow-up & analyzed by intention-to-treat), outcome reporting bias (all outcomes of interest defined & reported).

  • Variable risk of performance/detection bias:

    • Apixaban vs warfarin comparison was open-label (i.e. patients & clinicians aware of treatment assignment):

      • All outcomes were adjudicated by a blinded clinical endpoint committee, therefore providing some protection against (but not eliminating) detection bias.

    • Aspirin vs placebo comparison was blinded (patients, clinicians, outcome adjudicators unaware of treatment assignment): Low risk of performance & detection bias.

TRED-HF - Withdrawal of HF meds in patients with recovered (non-ischemic) dilated cardiomyopathy

Halliday BP, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet 2019 Jan 5;393(10166):61-73.

Bottom Line: In patients with recovered dilated cardiomyopathy (DCM), even careful withdrawal of HF medications will result in relapse of DCM (based on clinical signs, imaging or biomarkers) in approximately 4 out of 10 patients within 6 months, compared to no deterioration in this timeframe if these medications are continued.

These medications should be considered “lifelong” medications until we have tools that can reliably predict which patients can stop them without deteriorating.


  • In patients who initially have HF with reduced ejection fraction (HFrEF), recovery of ejection fraction >50% portends a more favorable prognosis

    • e.g. In one study, vs patients who had initial HFrEF followed by LVEF recovery to >50%, patients with non-recovered HFrEF had an increased risk of death, transplant or VAD placement (HR 3.4) & CV hospitalization (HR 1.8)

  • The 2017 Canadian Cardiovascular Society (CCS) heart failure (HF) guidelines recommend consideration of monitored, sequential discontinuation of HF meds in certain subsets of patients with recovered non-ischemic cardiomyopathy

    • Including: chemotherapy-related, ETOH overuse-related, peripartum, tachycardia-related, or valvular cardiomyopathy

    • If: Asymptomatic (NYHA 1), LVEF and LV volumes normalized, trigger eliminated (e.g. ETOH abstinence, HR controlled, valve repaired/replaced)

  • There is limited evidence for pharmacological treatment withdrawal in patients with HFrEF who get EF recovery

    • e.g. in an early observational study of 13 participants with DCM taking metoprolol for >2.5 years who weaned off metoprolol, 54% (7/13) experienced clinical deterioration (4 deaths & 3 patients who worsened by 1 NYHA functional class).

Design: Open-label RCT (pilot trial designed to plan larger trial)

Patients (n=51)

  • Included if:

    • 16+ y/o

    • Previous dx of dilated cardiomyopathy (DCM) with LVEF 40% or lower

    • Currently:

      • NYHA functional class 1 (no current HF symptoms)

      • LVEF 50% or higher & left ventricular end diastolic volume indexed (LVEDVi) WNL (based on cardiac MRI, or 3D echo if MRI contraindicated)

      • NT-proBNP <250 ng/L

      • Treatment with 1+ of the following HF meds: Loop diuretic, ACEI, ARB, mineralocorticoid-receptor antagonist (MRA; spironolactone or eplerenone)

  • Key exclusion criteria

    • Uncontrolled HTN (>160/100 mmHg in clinic)

    • Mod-severe valvular disease

    • Angina

    • Beta-blocker required for AF/flutter, VT, or SVT

    • GFR <30

    • Pregnant.

  • Baseline characteristics (average of both groups unless specified)

    • Median age 55 y/o (IQR 45-64), male (67%)

    • Time since dx (4.9 y), median LVEF at dx 25%

    • Cause: Idiopathic (69%), familial (14%), trigger (excess ETOH, pregnancy, anthracycline, hyperthyroidism or myocarditis; 18%), pathogenic TTN truncation (22%)

    • Time since LVEF >50% (2 y)

    • CV symptom burden (0=none, 185=severe): 10-11

    • Quality of life using Kansas City Cardiomyopathy Questionnaire (KCCQ; 0=worst, 100=best)): 94-97

    • LVEF 60%, LVEDVi 83 mL/m^2, NT-proBNP 72 ng/L

      • Global longitudinal strain median 14% (values <16% considered abnormal)

    • Meds: ACEI/ARB (100%), beta-blocker (88%), MRA (47%), loop diuretic (12%)

Intervention & Comparator

  • Intervention: Sequential discontinuation of HF meds over max 4 months, total 6 months follow-up

    • Order of drug dose reduction/discontinuation:

      • (1) Loop diuretic (reduced by 50% q2 weeks until furosemide 40 mg/d-equivalent, then D/Ced)

      • (2) MRA (reduced by 50% until equivalent to spiro 50 mg/d, then D/Ced)

      • (3) Beta-blocker (reduced by 50% until 25% target dose or lower, then D/Ced)

      • (4) ACEI/ARB (reduced by 50% until 25% target dose or lower, then D/Ced)

    • Follow-up schedule:

      • Baseline: Clinic visit, symptom & QoL questionnaire, exercise stress test, cardiac MRI, NT-proBNP

      • q4 weeks: Clinic visit & NT-proBNP

      • @ week 16: Repeat cardiac MRI

      • @ month 6: Same as baseline

  • Comparator:

    • Phase 1 (randomized phase) x6 months: Continued all HF meds per baseline

      • @ baseline & month 6: Same as intervention group

      • @ weeks 8 & 16: Clinic visit, NT-proBNP

    • Phase 2: Then, non-randomized crossover to sequential discontinuation of HF meds as per intervention protocol


Primary outcome: DCM relapse in 6-month randomized phase

  • Defined as meeting 1+ of:

    • Clinical HF based on signs & symptoms

    • LVEF reduced by >10%, to <50%

    • LVEDVi increased by >10%, to above normal range

    • NT-proBNP doubled, to >400 ng/L

  • Discontinuation group 44%, control group 0% (p=0.0001) - “number needed to harm” = 3 (rounded up from 2.3)

Figure 3 from TRED-HF. Kaplan-Meier curve of time to relapsed DCM comparing discontinuation versus continuation of HF meds

Secondary outcomes:

  • Composite safety outcome (CV death, major adverse CV events, unplanned CV hospitalization): 0 in both groups

  • (Select) differences in means between groups from baseline to month 6:

    • KCCQ: -5.1 (95% CI -9.9 to -0.4; lower with discontinuation vs continuation of HF meds)

    • LVEF -9.5% (lower with discontinuation vs continuation)

    • LVEDVi +4.7 mL/m^2 (95% CI -1.5 to +11.0, p=0.14)

    • Vitals: HR +15 bpm, BP +7/+7 mmHg

    • Inconclusive: CV symptom burden, exercise time, peak VO2, log-transformed NT-proBNP

Secondary analyses including withdrawals from phase 1 + phase 2

  • DCM relapse in control group phase 2: 36%

  • Overall DCM relapse rate after HF med discontinuation: 40% (26% relapse <2 months of discontinuation)

Figure 4 from TRED-HF. Venn diagram breakdown of component of primary outcome met (includes all withdrawals from randomized phase + single-arm crossover phase)

Figure 4 from TRED-HF. Venn diagram breakdown of component of primary outcome met (includes all withdrawals from randomized phase + single-arm crossover phase)

Internal validity

  • Allocation bias: Low risk

    • Computer-generated random sequence, 1:1 allocation in permuted blocks, stratified by baseline NT-proBNP

    • Centralized allocation via online system

  • Performance bias: Low/unclear risk

    • Patients & their clinicians aware of treatment allocation; however, the study employed a standardized protocol to wean & D/C HF meds, as well as standardized monitoring

  • Detection bias

    • Low risk of bias for objective outcomes (core lab MDs reading imaging unaware of study group allocation)

    • High risk of bias for QoL outcomes (patients completed the questionnaires aware of treatment allocation)

  • Attrition bias: Low risk

    • Loss to follow-up 2% (1 participant in withdrawal group left trial after 7 days)

    • Analyzed intention-to-treat population

Other Considerations

  • We can’t yet predict which stable, recovered DCM patients will deteriorate with D/C of HF meds

    • In this trial, predictors of DCM relapse after withdrawal of therapy included: greater age, use of >2 meds, use of MRA, higher NT-proBNP, lower global radial strain on cardiac MRI, & possibly lower peak VO2

      • However, based on univariable analysis only (no adjusting for other variables) & small n of events

    • DCM etiology did not clearly predict risk of deterioration with therapy withdrawal. Some patients with a seemingly reversible cause of DCM (e.g. ETOH use, pregnancy) did have DCM relapse upon D/Cing HF meds. Therefore, presence of a trigger does not indicate that D/Cing HF meds after HF remission will be safe.