Effects of omecamtiv mecarbil on haemodynamics in large animal models and clinical trials
| Study . | Species, condition . | Appl. . | n . | Time of OM admin. . | OM Plasma Conc. (ng/mL) . | SET . | SV . | HR . | C. O. . | SVR . | LVEDP . | LVEDV (LVEDD) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Shen | Dog MI/Pacing | i.v. | 6 | 15 min–72 h | ? | +20-30% | +44% | −15% | +22% | −15% | −17% | |
| Malik | Dog MI/Pacing | i.v. | 5 | 15 min | ? | +25% | +61% | −17% | +29% | |||
| Bakkehaug | Pig (stunning) | i.v. | 7 | 20 min | 500–1000 | +20% | 0 | 0 | 0 | −17% | −31% | −18% |
| Teerlink | Human Con | i.v. | 34 | 1–24 h | 400–500 | +18% | +11% | −3% | ||||
| Cleland | Human CHF | i.v. | 45 | 1.5–96 h | 400–500 | +19% | +13% | +9% | 0 | |||
| ATOMIC-HF | Human AHF | i.v. | 89 | 48 h | 300–787 | +17%a | 0 | −2 b.p.m. | 0 (EDD) | |||
| COSMIC | Human CHF | oral | 427 | 20 weeks | 318 | +8% | +7% | -4% | 0b | c | −2% (EDD) |
| Study . | Species, condition . | Appl. . | n . | Time of OM admin. . | OM Plasma Conc. (ng/mL) . | SET . | SV . | HR . | C. O. . | SVR . | LVEDP . | LVEDV (LVEDD) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Shen | Dog MI/Pacing | i.v. | 6 | 15 min–72 h | ? | +20-30% | +44% | −15% | +22% | −15% | −17% | |
| Malik | Dog MI/Pacing | i.v. | 5 | 15 min | ? | +25% | +61% | −17% | +29% | |||
| Bakkehaug | Pig (stunning) | i.v. | 7 | 20 min | 500–1000 | +20% | 0 | 0 | 0 | −17% | −31% | −18% |
| Teerlink | Human Con | i.v. | 34 | 1–24 h | 400–500 | +18% | +11% | −3% | ||||
| Cleland | Human CHF | i.v. | 45 | 1.5–96 h | 400–500 | +19% | +13% | +9% | 0 | |||
| ATOMIC-HF | Human AHF | i.v. | 89 | 48 h | 300–787 | +17%a | 0 | −2 b.p.m. | 0 (EDD) | |||
| COSMIC | Human CHF | oral | 427 | 20 weeks | 318 | +8% | +7% | -4% | 0b | c | −2% (EDD) |
From Shen et al.,84 Malik et al.,83 Bakkehaug et al.,86 Teerlink et al.,16 Cleland et al.,15 ATOMIC-HF,18 and COSMIC-HF.19
C. O., cardiac output; HR, heart rate; ICM, dog model of ischaemic cardiomyopathy; LVEDP, LV end-diastolic pressure; LVEDV(D), LV end-diastolic volume (dimension); n, number of animals/patients; SET, systolic ejection time; SV, stroke volume; SVR, systemic vascular resistance.
Estimated; no baseline SET indicated; assuming a SET of 316 ms as in Cleland et al. (2011).
Estimated from the least square mean changes in SV and HR.
Decrease of NT-proBNP by 970 pg/mL vs. placebo.
Effects of omecamtiv mecarbil on haemodynamics in large animal models and clinical trials
| Study . | Species, condition . | Appl. . | n . | Time of OM admin. . | OM Plasma Conc. (ng/mL) . | SET . | SV . | HR . | C. O. . | SVR . | LVEDP . | LVEDV (LVEDD) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Shen | Dog MI/Pacing | i.v. | 6 | 15 min–72 h | ? | +20-30% | +44% | −15% | +22% | −15% | −17% | |
| Malik | Dog MI/Pacing | i.v. | 5 | 15 min | ? | +25% | +61% | −17% | +29% | |||
| Bakkehaug | Pig (stunning) | i.v. | 7 | 20 min | 500–1000 | +20% | 0 | 0 | 0 | −17% | −31% | −18% |
| Teerlink | Human Con | i.v. | 34 | 1–24 h | 400–500 | +18% | +11% | −3% | ||||
| Cleland | Human CHF | i.v. | 45 | 1.5–96 h | 400–500 | +19% | +13% | +9% | 0 | |||
| ATOMIC-HF | Human AHF | i.v. | 89 | 48 h | 300–787 | +17%a | 0 | −2 b.p.m. | 0 (EDD) | |||
| COSMIC | Human CHF | oral | 427 | 20 weeks | 318 | +8% | +7% | -4% | 0b | c | −2% (EDD) |
| Study . | Species, condition . | Appl. . | n . | Time of OM admin. . | OM Plasma Conc. (ng/mL) . | SET . | SV . | HR . | C. O. . | SVR . | LVEDP . | LVEDV (LVEDD) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Shen | Dog MI/Pacing | i.v. | 6 | 15 min–72 h | ? | +20-30% | +44% | −15% | +22% | −15% | −17% | |
| Malik | Dog MI/Pacing | i.v. | 5 | 15 min | ? | +25% | +61% | −17% | +29% | |||
| Bakkehaug | Pig (stunning) | i.v. | 7 | 20 min | 500–1000 | +20% | 0 | 0 | 0 | −17% | −31% | −18% |
| Teerlink | Human Con | i.v. | 34 | 1–24 h | 400–500 | +18% | +11% | −3% | ||||
| Cleland | Human CHF | i.v. | 45 | 1.5–96 h | 400–500 | +19% | +13% | +9% | 0 | |||
| ATOMIC-HF | Human AHF | i.v. | 89 | 48 h | 300–787 | +17%a | 0 | −2 b.p.m. | 0 (EDD) | |||
| COSMIC | Human CHF | oral | 427 | 20 weeks | 318 | +8% | +7% | -4% | 0b | c | −2% (EDD) |
From Shen et al.,84 Malik et al.,83 Bakkehaug et al.,86 Teerlink et al.,16 Cleland et al.,15 ATOMIC-HF,18 and COSMIC-HF.19
C. O., cardiac output; HR, heart rate; ICM, dog model of ischaemic cardiomyopathy; LVEDP, LV end-diastolic pressure; LVEDV(D), LV end-diastolic volume (dimension); n, number of animals/patients; SET, systolic ejection time; SV, stroke volume; SVR, systemic vascular resistance.
Estimated; no baseline SET indicated; assuming a SET of 316 ms as in Cleland et al. (2011).
Estimated from the least square mean changes in SV and HR.
Decrease of NT-proBNP by 970 pg/mL vs. placebo.
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