Paradigm-HF: a Paradigm Shift in Heart Failure Treatment?

Application and impact of run-in studies

“…Notably, recent RCTs of other medications with runin phases [16][17][18] have reported rates of adverse events that some have speculated are artificially low. [19][20][21][22] For example, in PARADIGM-HF, patients were randomized to receive a neprilysin inhibitor (LCZ696) or enalapril after they completed three phases: a screening period, a run-in phase with enalapril, and then a run-in phase with LCZ696. 16 The authors stated that the multiple run-in phases were intended to "ensure an acceptable side-effect profile of the study drugs."…”

“…16 Some have argued that the rates of adverse events reported in PARADIGM-HF therefore underestimated the actual risks that might be expected of neprilysin inhibitors among "real-world" patients after FDA approval. [19][20][21]23 Our study has several limitations. We assessed the impact of run-in phases within a single class of medications, and thus our results might not be generalizable to other classes of medications.…”

PARADIGM-HF denemesinin sonuçlarını istatistiksel ve metodolojik bakış açısı ile farklı kılan özellikler nelerdir?

“…PARADIGM-HF'in bu şekilde dizayn edilmesi ile ilgili birtakım eleştiriler yapılmıştır. Örneğin, [14] Bir başka eleştiri ise, kontrol grubunda neden plasebo kullanılmadığı şeklindeydi. Ancak, yukarıda ki tabloda da belirtildiği gibi, kontrol grubunda renin-anjiyotensin blokerleri olmaksızın sadece plasebo kullanımı etik açıdan uygun değildir.…”