TABLE 4.
Incidence rates for cardiovascular event outcomes (MACE endpoints; all exposed patients) [92]
| Cardiovascular event parameter | Placebo (n = 1742) | PHEN/TPM-ER 3.75/23 (n = 240) | PHEN/TPM-ER 7.5/46 (n = 604) | PHEN/TPM-ER 15/92 (n = 1737) | PHEN/TPM-ER total (n = 2581) | Hazard ratiob (95% CI) |
| MACE endpointa | ||||||
| Cardiovascular death, MI, stroke | 0.3 | 0.5 | 0.3 | 0.2 | 0.3 | 0.84 (0.26, 2.64) |
| Jupiter MACE | 0.6 | 0.5 | 0.3 | 0.3 | 0.3 | 0.55 (0.21, 1.42) |
| US FDA MACE | 0.6 | 0.5 | 0.3 | 0.3 | 0.3 | 0.49 (0.19, 1.25) |
| Modified US FDA MACE | 0.8 | 0.5 | 0.6 | 0.5 | 0.5 | 0.62 (0.29, 1.33) |
| Cardiac disorders SOC SAEs | 0.6 | 0.5 | 0.6 | 0.3 | 0.4 | 0.68 (0.28, 1.68) |
| Cardiovascular/neurovascular SAEs | 1.5 | 1.0 | 0.9 | 0.7 | 0.8 | 0.54 (0.29, 0.98) |
CI, confidence interval; MACE, major adverse cardiovascular event; MedDRA, Medical Dictionary for Regulatory Activities; MI, myocardial infarction; PHEN/TPM-ER, phentermine and topiramate extended-release; SAE, serious adverse event; SOC, system organ class; US FDA, US Food and Drug Administration.
aComposite endpoint definitions: Jupiter MACE – cardiovascular death, myocardial infarction, stroke, coronary revascularization, and unstable angina; US FDA MACE – cardiovascular death, stroke, coronary revascularization, unstable angina, and congestive heart failure; modified US FDA MACE – cardiovascular death, acute coronary syndrome (nonfatal transient ischaemic attack), coronary revascularization, hospitalization for heart failure, stent thrombosis, hospitalization for other cardiovascular causes, carotid artery revascularization, peripheral vascular revascularization, lower extremity amputation, hospitalization for cardiac arrhythmia; cardiac disorders SOC SAEs – all SAE-preferred terms mapping to MedDRA; cardiovascular and neurovascular SAEs – all SAE-preferred terms mapping to the MedDRA Cardiac Disorders SOC, and SAEs with preferred terms of deep vein thrombosis, hypertension, hypotension, brain stem infarction, cerebral infarction, cerebrovascular accident, haemorrhage intracranial, transient ischaemic attack, chest pain, non-cardiac chest pain, and pulmonary embolism.
bHazard ratio is from a univariate Cox proportional hazards regression analysis comparing PHEN/TPM-ER total to placebo.