Announcements Thank you attending the ACCP Cardiology PRN Journal Club Thank you if you attended last time Thank you for doing the survey after second journal club Changes we made include Only have 1 resident at time ID: 427662
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Slide1
ACCP Cardiology PRN Journal ClubSlide2
Announcements
Thank you attending the ACCP Cardiology PRN Journal Club
Thank you if you attended last time
Thank you for doing the survey after second journal club
Changes we made include:
Only have 1 resident at time
Improve sound
Changed format with mentors
Offering recordings of the presentations
Our summary article from first journal club will be up soon! I can e-mail if you would like a copy for now.Slide3
Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT)
Janna Beavers,
PharmD
PGY2 Cardiology Resident
WakeMed
Health & Hospitals
Raleigh, NCSlide4
Disclosure Statement
Janna Beavers has no conflicts
of interest to disclose.Slide5
Background
JACC
; 2013:62(16):e147-239
Eur
Heart J
2012(33):1787-1847Slide6
Background
JAMA
2013;300(8):781-797Slide7
TOPCAT Study Objective
Determine whether treatment with spironolactone would improve clinical outcomes in patients with symptomatic heart failure with preserved ejection fraction.
NEJM
2014;370:1383-1392Slide8
Study Population
Inclusion Criteria
Exclusion Criteria
50 years of age or older
At
least one sign and at least one symptom of heart failure
EF
≥45%
Controlled BP (SBP<140 mmHg or ≤160 mmHg if patients are taking 3 or more meds)
Potassium <5
mmol
/L
Hx
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;370:1383-1392Slide9
Study Design
International, multi-center, double-blind, placebo-controlled, randomized trial
Randomization
Study Groups
Spironolactone 15 mg once daily (max 45 mg/day)
Placebo
Stratification
Previous hospitalization or BNP elevation
Patients received other heart failure medications throughout study
NEJM
2014;370:1383-1392
Medication
Spironolactone
Placebo
Diuretics
81.4%
82.3%
Beta blocker
84.3%
84.2%ACEi or ARB78.2%77.3%Slide10
Outcomes
NEJM
2014;370:1383-1392Slide11
Statistics & Enrollment
Statistics
3,515 subjects (551 events) required to detect 20% relative reduction in composite primary outcome
80% power
Intention to treat analysis
Enrollment
N=3,445
Mean follow-up = 3.3 years
Regions:
Americas (N=1,767)
Eastern Europe (N=1,678)
Mean dose at 8 months: spironolactone 25 mg, placebo 28 mg
NEJM
2014;370:1383-1392Slide12
Baseline Characteristics
NEJM
2014;370:1383-1392Slide13
Outcomes
NEJM
2014;370:1383-1392Slide14
Subgroup Analysis
Outcome
Hospitalization (
n=2464)
Elevated BNP (n=981)
Spiro
(n=1232)
Placebo (n=1232)
HR
(p-value)
Spiro (n=490)
Placebo (n=491)
HR
(p-value)
Primary Outcome
19.6%
19.1%
1.01 (p=0.923)
15.9%
23.6%0.65 (p=0.003) CV Mortality9.7%9.5%1.01 (p=0.924)
8.2%
12%
0.69 (p=0.069)
Aborted cardiac arrest
0.1%
0.4%
0.2 (p=0.138)
0.4%
0
N/A
Hospitalization for heart failure
12.3%
13.1%
0.92 (0.44)
11.2%
16.9%
0.64 (p=0.011)
NEJM
2014;370:1383-1392Slide15
Post-hoc Analysis
Outcome
Americas
Eastern Europe
Spiro (n=886)
Placebo (n=881)
HR
(p-value)
Spiro
(n=836)
Placebo (n=842)
HR
(p-value)
Primary Outcome
27.3%
31.8%
0.82 (p=0.026)
9.3%
8.4%
1.1 (p=0.576)Adjusted Cox Model: HR 3.96, p<0.001 NEJM 2014;370:1383-1392Slide16
Safety
NEJM
2014;370:1383-1392Slide17
Author’s Conclusions
In patients with
HFpEF
, spironolactone did NOT significantly reduce the incidence of the primary outcome.
Spironolactone -> reduced hospitalizations
NEJM
2014;370:1383-1392Slide18
Study Critique
Strengths
Limitations
First
large study of aldosterone antagonists in
HFpEF
to look at morbidity and mortality
Doses achieved similar to other HF
studies (i.e., RALES)
Fewer HF hospitalizations in spironolactone group
Mild
adverse event profile for spironolactone
Inclusion
criteria for hospitalization:
Major component of hospitalization was heart failure but no standard diagnosis
Different
standards of care and definitions of heart failure in different countries
Not
powered to detect differences in subgroup or post-hoc analysesSlide19
Impact on Clinical Practice
Increased use of aldosterone antagonists in patients with
HFpEF
?
Particularly those with elevated BNP
Future Studies
Geographic regions
Include only patients with elevated BNP Slide20
Acknowledgements
Carolyn Hempel,
PharmD
, BCPS
State University of New York at Buffalo, School of Pharmacy and Pharmaceutical Sciences
Jenna Huggins,
PharmD
, BCPS-AQ Cardiology
WakeMed
Health & Hospitals
Herb Patterson,
PharmD
, FCCP
UNC
Eshelman
School of Pharmacy
Craig
Beavers,
PharmD
, AACC, BCPS-AQ CardiologyTriStar Centennial Medical CenterSlide21
Questions??Slide22
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 e-mail the journal club at
accpcardsprnjournalclub@gmail.com
or
craig.beaverspharmd@gmail.com
Our next Journal Club will be November 25
th
, same time.
Robert
Tunny
from Vanderbilt
Medical Center
will be presenting PARADIGM-HF