2 Announcements Thank you attending the ACCP Cardiology PRN Journal Club Thank you if you attended last timeThank you for doing the survey after second journal clubChanges we made include:Only have 1 resident at timeImprove soundChanged format with mentorsOffering recordings of the presentationsOur summary article from first journal club will be up soon! I can if you would like a copy for now.
3 Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT) Janna Beavers, PharmDPGY2 Cardiology ResidentWakeMed Health & HospitalsRaleigh, NCTOPCAT = Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist
4 Janna Beavers has no conflicts of interest to disclose. Disclosure StatementJanna Beavers has no conflicts of interest to disclose.
6 BackgroundRAAS ActivationAngiotensin II increased release of aldosteroneAldosterone: sodium/water retention, fibrosis, vascular inflammation, hypertrophyAldo-DHFNo change in exercise capacity, symptoms, quality of lifeImproved LV diastolic function at 12 monthsJAMA 2013;300(8):
7 TOPCAT Study Objective Determine whether treatment with spironolactone would improve clinical outcomes in patients with symptomatic heart failure with preserved ejection fraction.NEJM 2014;370:
8 Study Population Inclusion Criteria Exclusion Criteria 50 years of age or olderAt least one sign and at least one symptom of heart failureEF≥45%Controlled BP (SBP<140 mmHg or ≤160 mmHg if patients are taking 3 or more meds)Potassium <5 mmol/LHx of hospitalization within 12 months (major component of hospitalization is management of HF) OR elevated BNP within 60 days (BNP≥100 pg/mL or NT-proBNP≥360 pg/mL)Severe systemic illness (life-expectancy <3 years)Severe renal dysfunction (GFR<30 mL/min/1.73m2 or SCr ≤2.5 mg/dL)Specific coexisting conditions (i.e., COPD requiring oxygen, atrial fibrillation with resting HR >90, MI/PCI/CABG in the past 90 days)NEJM 2014;370:
9 Study DesignInternational, multi-center, double-blind, placebo-controlled, randomized trialRandomizationStudy GroupsSpironolactone 15 mg once daily (max 45 mg/day)PlaceboStratificationPrevious hospitalization or BNP elevationPatients received other heart failure medications throughout studyMedicationSpironolactonePlaceboDiuretics81.4%82.3%Beta blocker84.3%84.2%ACEi or ARB78.2%77.3%NEJM 2014;370:
10 Outcomes Primary Outcome Secondary Outcomes Composite – death from CV causes, aborted cardiac arrest, hospitalization for management of HFSecondary OutcomesDeath from any causeHospitalization for any causeHyperkalemia (K≥5.5 mmol/L) or hypokalemia (K<3.5 mmol/L)Elevated SCr (≥2 times above the upper limit of normal OR SCr ≥3 mg/dL)NEJM 2014;370:
11 Statistics & Enrollment 3,515 subjects (551 events) required to detect 20% relative reduction in composite primary outcome 80% powerIntention to treat analysisN=3,445Mean follow-up = 3.3 yearsRegions:Americas (N=1,767)Eastern Europe (N=1,678)Mean dose at 8 months: spironolactone 25 mg, placebo 28 mgNEJM 2014;370:
12 Baseline Characteristics Age 68.7 yrs (median)~89% white raceNYHA II (~64%) & III (~33%)Ejection fraction 56% (median)SCr ~1 (median)Eligibility based on hospitalization (71.5%) or elevated BNP (28.5%)NEJM 2014;370:
16 D/C due to breast tenderness SafetySpironolactonePlaceboDoubling of SCrD/C due to breast tenderness↓ Systolic BP↑ Hyperkalemia↑ HypokalemiaNEJM 2014;370:
17 Author’s ConclusionsIn patients with HFpEF, spironolactone did NOT significantly reduce the incidence of the primary outcome. Spironolactone -> reduced hospitalizationsNEJM 2014;370:
18 Study Critique Strengths Limitations First large study of aldosterone antagonists in HFpEF to look at morbidity and mortalityDoses achieved similar to other HF studies (i.e., RALES)Fewer HF hospitalizations in spironolactone groupMild adverse event profile for spironolactoneInclusion criteria for hospitalization: Major component of hospitalization was heart failure but no standard diagnosisDifferent standards of care and definitions of heart failure in different countriesNot powered to detect differences in subgroup or post-hoc analyses
19 Impact on Clinical Practice Increased use of aldosterone antagonists in patients with HFpEF?Particularly those with elevated BNPFuture StudiesGeographic regionsInclude only patients with elevated BNP
20 Acknowledgements Carolyn Hempel, PharmD, BCPS State University of New York at Buffalo, School of Pharmacy and Pharmaceutical SciencesJenna Huggins, PharmD, BCPS-AQ CardiologyWakeMed Health & HospitalsHerb Patterson, PharmD, FCCPUNC Eshelman School of PharmacyCraig Beavers, PharmD, AACC, BCPS-AQ CardiologyTriStar Centennial Medical Center
22 Thank you for attending! If you would like to have your resident present, would like to be a mentor, or have questions or comments please the journal club at orOur next Journal Club will be November 25th, same time.Robert Tunny from Vanderbilt Medical Center will be presenting PARADIGM-HF