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Responder analysis

treated patients, proportions that increased by 8% and fell by 8%, respectively at 16 weeks.

Right atrial pressure (RAP) <8mmHg was found in 45% of patients receiving riociguat and 44% of those taking placebo at baseline. At 16 weeks, the proportion of riociguat-treated patients with RAP <8mmHg had increased by 14% in the riociguat group and by 12% in the placebo-treated group. In terms of cardiac index, similar proportions – 32% for the riociguat group and 29% for placebo-treated patients – had an index of ≥2.5l/min/m2

Those proportions increased to 58% among patents taking riociguat and fell marginally to 28% among those taking placebo.

At baseline, SvO2 levels of ≥65% were

recorded in 42% of both riociguat and placebo-treated groups. After 16 weeks it was observed that the proportion of riociguat-treated patients achieving the threshold was up by 12% whereas the proportion of those in the placebo group with SvO2

≥65% had fallen by 7%.

Compared with baseline values (25% for the riociguat group and 27% for the placebo group), the proportion of patients with a PVR <500dyn•sec•cm–5

, 40

which, as mentioned previously, is a parameter known to be associated with

survival in CTEPH, doubled to 50% in the riociguat group and remained almost unchanged for patients taking placebo at 26%.

To look at the robustness of their conclusion, the authors applied a combined response threshold of 6MWD ≥380m, WHO FC I/II, cardiac index ≥2.5l/min/m2

and SVO2

, NT-proBNP <1800pg/ml ≥65%, as for the PATENT-1


data: with a significant (p=0.0007) result in favour of riociguat (25%) versus placebo (6%; approximately 10% lower for both groups compared with PATENT-1).

The authors note that ‘most

responder analysis studies performed to date have been undertaken in patients with PAH, and the threshold values for 6MWD, WHO FC, NT-proBNP, SvO2, RAP, and cardiac index used in the current analysis were based on these data. No single parameter has been found to correlate consistently with survival in patients with PAH. Current treatment guidelines recommend assessing multiple parameters when monitoring the efficacy of a therapy. More recently, updated treatment goals for PAH include New York Heart Association functional class I or II, 6MWD ≥380m to 440m, cardiopulmonary exercise test –

measured peak oxygen consumption 415ml/min/kg and ventilator equivalent for carbon dioxide <45l/min, brain natriuretic peptide levels toward ‘normal,’ echocardiography and/or cardiac magnetic resonance imaging demonstrating normal/near-normal right ventricular size and function, and haemodynamics showing normalisation of right ventricular function with RAP <8mmHg and cardiac index >2.5–3l/min/m2

.’1 The authors say that ‘…the

improvement in multiple parameters with riociguat compared with placebo in CHEST-1 may be indicative of a beneficial effect on survival.’ However, they remind readers that the treatment goals are not defined and validated for patients with CTEPH per se, rather mainly for those with PAH. And while there are similarities between the two conditions, there are also fundamental and significant differences, not least in terms of pathophysiology, diagnosis and treatment response. In conclusion, the authors say that the exploratory analysis of CHEST-1 shows that treatment with riociguat may increase the proportion of patients who achieve clinically relevant responder thresholds. They recommend caution when extrapolating responder thresholds for

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