PH-Targeted Therapies Show Modest-at-Best Benefit in PH Due to Left Heart Disease, Review Study Reports

Stacy Grieve, PhD avatar

by Stacy Grieve, PhD |

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A large review of clinical trials evaluating whether pulmonary hypertension (PH)-targeted therapies can improve exercise capacity in patients with pulmonary hypertension due to left heart disease (PH-LHD) found varying effectiveness and modest benefit.

The findings were reported in the study “Pulmonary hypertension-targeted therapies in heart failure: A systematic review and meta-analysis,” published in the journal PLOS One

The most common type of PH is due to left heart failure, where the heart’s left ventricle pumps significantly less blood.  It is estimated that almost 80% of patients with LHD will go on to develop pulmonary hypertension. Furthermore, symptoms in patients with PH-LHD are often more severe, with evidence of poorer exercise capacity and an increased risk of mortality in these people compared to LHD patients without PH.

The combination of both heart failure and pulmonary dysfunction make treating PH-LHD difficult. Treatments that can improve heart function, for instance, may have limited effects on improving pulmonary function.

Some studies suggest that therapies used to treat pulmonary arterial hypertension (PAH) may be effective in PH-LHD patients. But these studies were often small, used different therapies, and have conflicting results.

Researchers in Canada looked at all  clinical studies published between January 1990 and July 2017 that evaluated PH-targeted therapies in patients with LHD. A total of 22 studies, representing 5,448 patients, assessed exercise tolerance after treatment with PH-targeted therapies.

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Therapies used included endothelial receptor antagonists, PDE5-inhibitors, prostanoids, and soluble guanylate cyclase stimulators. The duration of the trials ranged from 12 to 52 weeks (median of 22 weeks), and included mostly Caucasians. Most patients had moderate heart function, classified as New York Heart Association (NYHA) functional class II or III (on a scale of I-IV).

PH-targeted therapies were associated with a “modest” improvement in exercise capacity in PH-LHD patients, primarily in studies that tested PDE5-inhibitors and prostanoids. However, there was a significant amount of variation in the outcomes of these studies.

The research team also reported that several of these studies had a high risk of bias; bias in these type of studies can lead to an overestimation or underestimation of true effect. Therefore, results from these studies should be regarded carefully, the team emphasized.

A lesser variation in outcomes was seen when studies with low or unknown risk of bias were included, but the improvement in exercise capacity seen with PH-targeted therapies was still quite modest.

PH-targeted therapies were also linked to a significant rise in treatment discontinuation compared to standard treatment, suggesting they are not well-tolerated by the patients. There were no significant differences in mortality rates.

Researchers concluded that despite the current use of PH-targeted therapies in the clinical management of PH-LHD, the results of their study “do not provide evidence to support the use of these drugs in the clinical management of patients until future trials provide stronger evidence of safety and efficacy.”