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TABLE 1 . Secondary Endpoints
Secondary Endpoint
Dyspnea numerical response AUC through day 5 **
Patient global assessment response
Death or worsening HF within 7 days
Length of initial hospital stay , median days ( 95 % CI )
Days alive out of hospital through 30 days , median ( 95 % CI )
NT-proBNP change from baseline ( pg / ml ) at 48 hours , median ( 95 % CI )
Pooled Placebo ( n = 303 )
3.5 ( 3.3 to 3.8 )
127 ( 41.9 )
52 ( 17.2 )
9 ( 8 to 9 )
22 ( 21 to 23 )
-1,805 ( -2,271 to -1,370 )
Placebo ( n = 103 )
3.6 ( 3.1 to 4.0 )
35 ( 34.0 )
25 ( 24.3 )
9 ( 8 to 10 )
22 ( 21 to 23 )
-1,602 ( -2,099 to -797 )
Cohort 1 Cohort 2 Cohort 3
OM ( n = 103 )
3.5 ( 3.1 to 3.9 )
44 ( 42.7 )
13 ( 12.6 ) p = 0.027 *
8 ( 7 to 9 )
22 ( 21 to 23 )
-2,076 ( -2,746 to -1292 )
Placebo ( n = 99 )
3.2 ( 2.8 to 3.6 )
50 ( 50.5 )
15 ( 15.2 )
8 ( 7 to 9 )
23 ( 22 to 24 )
-1,987 ( -3,373 to -1695 )
OM ( n = 99 )
3.6 ( 3.2 to 4.0 )
48 ( 48.5 )
9 ( 9.1 )
7 ( 7 to 8 )
23 ( 23 to 24 )
-2,161 ( -4,273 to -1,336 )
Placebo ( n = 101 )
3.8 ( 3.4 to 4.3 )
42 ( 41.6 )
12 ( 11.9 )
9 ( 9 to 11 )
21 ( 20 to 23 )
-1788 ( -2,805 to -890 )
OM ( n = 101 )
3.7 ( 3.3 to 4.0 ) p = 0.038 *
51 ( 50.5 )
9 ( 8.9 )
9 ( 8 to 10 )
22 ( 21 to 23 )
-1742 ( -2,517 to -1,017 )
Values are mean ( 95 % confidence interval ) or n (%) unless otherwise indicated .
* Nominal p value compared to matching placebo from same cohort ; all others nonsignificant . ** Smaller value indicates better dyspnea condition . Analysis of covariance model least square mean ( SE ) for the 6 cohort / treatment arm , when compared within the same cohort , are 3.6 ( 0.2 ), 3.4 ( 0.2 ), 3.4 ( 0.2 ), 3.4 ( 0.2 ), 4.1 ( 0.2 ), 3.6 ( 0.2 ).
AUC = area under the curve
TABLE 2 . Adverse Events
Patient Incidence
Pooled Placebo ( n = 303 )
Pooled OM ( n = 303 )
Cohort 1 OM ( n = 103 )
Cohort 2 OM ( n = 99 )
Cohort 3 OM ( n = 101 )
All AEs 191 ( 63.0 ) 177 ( 58.4 ) 73 ( 70.9 ) 49 ( 49.5 ) 55 ( 54.5 ) 3 most common AEs
Cardiac failure * 53 ( 17.5 ) 46 ( 15.2 ) 17 ( 16.5 ) 14 ( 14.1 ) 15 ( 14.9 ) Hypokalemia 18 ( 5.9 ) 20 ( 6.6 ) 7 ( 6.8 ) 7 ( 7.1 ) 6 ( 5.9 ) Hypotension 14 ( 4.6 ) 24 ( 7.9 ) 14 ( 13.6 ) 5 ( 5.1 ) 5 ( 5.0 ) All serious AEs 70 ( 23.1 ) 66 ( 21.8 ) 24 ( 23.3 ) 24 ( 24.2 ) 18 ( 17.8 ) 3 most common serious AEs Cardiac failure * 29 ( 9.6 ) 26 ( 8.6 ) 8 ( 7.8 ) 11 ( 11.1 ) 7 ( 6.9 ) Acute renal failure 4 ( 1.3 ) 6 ( 2.0 ) 2 ( 1.9 ) 2 ( 2.0 ) 2 ( 2.0 ) Hypotension 0 ( 0.0 ) 3 ( 1.0 ) 3 ( 2.9 ) 0 ( 0.0 ) 0 ( 0.0 )
Deaths through 30 days 10 ( 3.3 ) 8 ( 2.6 ) 1 ( 1.0 ) 4 ( 4.0 ) 3 ( 3.0 ) HF 9 ( 3.0 ) 4 ( 1.3 ) 0 ( 0.0 ) 2 ( 2.0 ) 2 ( 2.0 ) Sudden cardiac death 1 ( 0.3 ) 2 ( 0.6 ) 1 ( 1.0 ) 1 ( 1.0 ) 0 ( 0.0 ) MI 0 ( 0.0 1 ( 0.3 ) 0 ( 0.0 ) 0 ( 0.0 ) 1 ( 1.0 ) Other cardiovascular 0 ( 0.0 ) 1 ( 1.0 ) 0 ( 0.0 ) 0 ( 0.0 ) 1 ( 1.0 )
AEs leading to discontinuation of Investigational Product
15 ( 5.0 ) 15 ( 5.0 ) 7 ( 6.8 ) 4 ( 4.0 ) 4 ( 4.0 )
Number of subjects reporting AEs of ischemic heart disease , MI , troponins increased |
5 ( 1.7 ) |
9 ( 3.0 ) |
2 ( 1.9 ) |
2 ( 2.0 ) |
5 ( 5.0 ) |
Number of subjects reporting AEs of SVT or VT |
34 ( 11.2 ) |
26 ( 8.6 ) |
13 ( 12.6 ) |
5 ( 5.1 ) |
8 ( 7.9 ) |
SVT |
20 ( 6.6 ) |
11 ( 3.6 ) |
6 ( 5.8 ) |
0 ( 0.0 ) |
5 ( 5.0 ) |
AF or atrial flutter |
16 ( 5.3 ) |
7 ( 2.3 ) |
3 ( 2.9 ) |
0 ( 0.0 ) |
4 ( 4.0 ) |
Ventricular tachyarrhythmias |
18 ( 5.9 ) |
16 ( 5.2 ) |
8 ( 7.8 ) |
5 ( 5.1 ) |
3 ( 3.0 ) |
beta blockers or MRAs .“ The researchers also noted that a related study looking at an oral version of OM ( COSMIC-HF ), taken with the ATOM- IC-AHF results , would provide guidance for the design of future trials .
“ Data from COSMIC-HF data were quite encouraging and were presented in the LBCT session at the American Heart Association Congress in November 2015 ,” they said . “ The results of COSMIC-HF have informed the potential Phase 3 designs being considered . “
The authors reported no surprises in the data , and also expressed encouragement at the low incidence of severe adverse events .
“ Overall , we think ATOMIC-AHF was an important step in further defining the pharmacokinetics , safety , and potential efficacy of OM in an AHF setting .” ■
PAPER CITATION Teerlink J , Felker M , McMurray J , et al . J Am Coll Cardiol . 2016 ; 67:1444-55 .
REFERENCES 1 . Felker GM , Pang PS , Adams KF , et al . Circ Heart
Fail . 2010 ; 3:314-25 .
2 . Hasenfuss G , Teerlink JR . Eur Heart J . 2011 ; 32:1838-45 .
3 . Teerlink J , Felker M , McMurray J , et al . J Am Coll Cardiol . 2016 ; 67:1444-55 .
Disclosures : This study was funded by Amgen , Inc ., in collaboration with Cytokinetics , Inc . Dr . Teerlink has received research grants from Amgen , Inc ., Cytokinetics , Mast Therapeutics , Novartis , Sorbent , and Trevena , and has served as a consultant to Amgen , Inc ., Cytokinetics , Mast Therapeutics , Novartis , and Trevena . Dr . Malik is an employee of Cytokinetics , Inc ., and is a stockholder in the company .
Values are n (%). * Cardiac failure includes both “ Cardiac failure ” and “ Cardiac failure congestive ” preferred terms . AE = adverse event ; SVT = supraventricular tachyarrhythmias ; VT = ventricular tachyarrhythmias ; other abbreviations as in TABLE 1 .