 A review published in 2015 concluded that these agents, when used in patients with high LDL-particle concentrations (thus at greatly elevated risk for cardiovascular disease) seem to be safe and effective at reducing all-cause mortality, cardiovascular mortality, and heart attacks.However more recent reviews conclude that while PCSK9 inhibitor treatment provides additional benefits beyond maximally tolerated statin therapy in high-risk individuals, PCSK9 inhibitor use probably results in little or no difference in mortality.Regeneron Pharmaceuticals (in collaboration with Sanofi) became the first to market a PCSK9 inhibitor, with a competitor Amgen reaching market slightly later.