Sildenafil worked in pulmonary hypertension due to CHF with preserved EF (RCT, Circulation) - PulmCCM
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Dec 262011
 

See Update Below: the larger RELAX trial (enrolling patients with less severe pulmonary hypertension) did not show a benefit of sildenafil.

Guazzi et al randomized 44 people with heart failure with preserved ejection fraction and associated pulmonary hypertension (confirmed by right heart catheterization) to receive the phosphodiesterase-5 inhibitor sildenafil or placebo for one year, along with standard therapy. Those in the sildenafil group experienced improvement in cardiac output and reduction in pressures on both the left and right sides of the heart (right atrial pressure, pulmonary artery, pulmonary vascular resistance, and wedge pressures). DLCO also improved. Improved diuresis in the treatment group did not appear to be responsible.

After past failures to show a benefit from endothelin antagonists or prostacyclin analogues in PAH due to heart failure, this trial may open the door to wider use of sildenafil for heart failure with preserved ejection fraction with associated pulmonary hypertension. However, it’s way too small a sample to draw firm conclusions or change clinical practice.

Wait for results from the  larger RELAX trial to help better answer the question of the role of vasodilator therapy for WHO group II pulmonary hypertension (i.e., owing to left heart disease). Circulation 2011;124:164-174.

Update: the larger RELAX trial published in JAMA 2013 showed no benefit of sildenafil in patients with CHF with preserved EF. Almost all of the enrollees had pulmonary hypertension (estimated by echocardiography but unconfirmed by right heart catheterization), with less severe PH than the patients in Guazzi et al. RELAX strongly suggests that there is no benefit of sildenafil in most patients with heart failure with preserved ejection fraction who also have pulmonary hypertension on echocardiography.

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  3 Responses to “Sildenafil worked in pulmonary hypertension due to CHF with preserved EF (RCT, Circulation)”

  1. [...] vascular disease and could theoretically benefit from pulmonary vasodilator therapy. In fact, a small trial suggested potential benefit of PDE-5 inhibitors in patients with heart failure and a preserved [...]

  2. The RELAX study does not refute the results of the Guazzi et al study. These two investigations had very different enrollment criteria, with Guazzi including a very specific subset of patients with HFpEF-PH and markedly elevated right atrial pressure, whereas the RELAX study was a HFpEF trial that did not require PH for enrollment. RELAX informs us that sildenafil did not change exercise capacity in those with HFpEF, while Guazzi et al suggest that there may be a subtype of HFpEF-PH that may benefit from PDE-5 inhibition, although this remains to be confirmed.

  3. Thanks Matthew. I’ll soften the wording to something other than “refute” based on your comment. You’re right the trials had different enrollment criteria. However, RELAX to me still provides a strong argument against giving PDE-5 inhibitors to most patients with pulmonary hypertension due to left sided CHF.

    The fact that RELAX did not require PH for enrollment is a distinction without a difference — since almost all the patients probably had PH (accepting that we don’t know their exact right atrial pressures since right heart cath was not done): the average estimated pulmonary artery pressure by echocardiography was 41, with more than 75% of the patients greater than 33 mm Hg (and probably >90% over 25 mm Hg). Despite the absence of invasive measurements, it’s still persuasive given the rough correlation between echocardiography and invasive measurements of PA pressure.

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