journal club
DESCRIPTION
Jim Hoehns, Pharm.D. Journal Club. HF r EF and HF p EF. TOPCAT - HF p EF. Randomized, double-blind trial, N=3,445 Mean duration: 3.3 years Sponsor: NHLBI Treatment Spironolactone 15mg QD; increased to max of 45mg/day by month 4 Placebo Outcome - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/1.jpg)
Journal Club
Jim Hoehns, Pharm.D.
![Page 2: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/2.jpg)
HFrEF and HFpEFClassification EF (%) DescriptionHF with reduced EF (HFrEF)
≤40 “systolic HF”; RCTs have mainly enrolled these HF patients; only in these pts have efficacious therapies been demonstrated
HF with preserved EF (HFpEF)
≥50 “diastolic HF”; dx is challenging due to excluding other noncardiac causes of symptoms suggestive of HF; efficacious therapies have not been identified
HFpEF, borderline 41-49 Characteristics, treatment patterns, and outcomes appear similar to those of pts with HFpEF
HFpEF, improved >40 Subset of pts who previously had HFrEF
![Page 3: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/3.jpg)
![Page 4: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/4.jpg)
TOPCAT - HFpEF Randomized, double-blind trial, N=3,445
Mean duration: 3.3 years Sponsor: NHLBI
Treatment Spironolactone▪ 15mg QD; increased to max of 45mg/day by month 4
Placebo Outcome
Primary: death from CV causes, aborted cardiac arrest, or hospitalization for HF
Endpoints adjudicatedN Engl J Med 2014;370:1383-92.
![Page 5: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/5.jpg)
TOPCAT - Methods Inclusion criteria
≥ 50 years of age At least one sign of HF (at screening)▪ PND, orthopnea, or dyspnea with exertion
At least one symptom of HF (w/i 1 year)▪ Rales, ↑JVD, edema, or + CXR (effusions, cardiomegaly)
LVEF ≥45% BP: SBP <140 or SBP <160 (if on ≥3 BP meds) K+ < 5.0 HF hospitalization within previous 12 months (non-
adjudicated) OR BNP >100 or NT-proBNP >360
![Page 6: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/6.jpg)
TOPCAT – Methods
Exclusion criteria GFR <30 ml/min Scr ≥2.5 mg/dL COPD requiring steroids, home oxygen, or
hospitalized exacerbation within 1 yr Stats
Intention-to-treat Power: 80% to detect 20% relative reduction Assumption: 17.4% outcome rate at 3 yrs▪ Target enrollment is 3,515
![Page 7: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/7.jpg)
TOPCAT - Methods
Enrollment (2006 – 2012); 233 sites – 6 countries USA: 1151 Canada: 326 Brazil: 167 Argentina: 123 Russia: 1066 Georgia: 612
![Page 8: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/8.jpg)
![Page 9: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/9.jpg)
![Page 10: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/10.jpg)
![Page 11: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/11.jpg)
TOPCAT - Results Dosage
Mean dose: 25 mg/day Discontinued study participation
Spironolactone: 9.3% Placebo: 8.8%
Permanently discontinued study drug Spironolactone: 34.3% Placebo: 31.4%
SBP changes at 8 months Spironolactone: -2.7 mm Hg Placebo: -0.2 mm Hg (P<0.001)
![Page 12: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/12.jpg)
TOPCAT – Dosage at 8 Months
![Page 13: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/13.jpg)
![Page 14: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/14.jpg)
![Page 15: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/15.jpg)
Analysis of total HFHospitalizations:
Spiro: 6.8/100person-yearsPlacebo: 8.3/100 person-years(P=0.03)
![Page 16: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/16.jpg)
Subgroup Analyses by Randomization
![Page 17: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/17.jpg)
Subgroup Analyses by Region
![Page 18: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/18.jpg)
Early Permanent Drug Discontinuation
![Page 19: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/19.jpg)
Reasons for Drug Discontinuation
![Page 20: Journal Club](https://reader036.vdocument.in/reader036/viewer/2022070423/568166ee550346895ddb43f5/html5/thumbnails/20.jpg)
Summary Spironolactone did not reduce primary
outcome in HFpEF Adequately powered for primary outcome Spironolactone associated with 36% RRR in
HF hospitalizations among BNP enrolled stratum
Were patients enrolled in Russia/Georgia (i.e. more likely to be in prior HF hospitalization stratum) less likely to have actual heart failure?
If HFpEF and elevated BNP, spironolactone worth consideration