Pulmonary hypertension-targeted therapies in heart failure: A systematic review and meta-analysis

Abstract

BackgroundPulmonary hypertension (PH) due to left heart failure (HF) is the most common form of PH. However, treatment is unclear because there are conflicting results about safety and efficacy of PH-targeted therapies.ObjectivesTo assess the effects of PH-targeted therapy on exercise capacity in HF patients.MethodsMEDLINE, EMBASE and the Cochrane Library were searched from January 1990 to July 2017 for randomized controlled trials comparing PH-targeted therapies to conventional therapy in HF. The primary outcome was to assess the effects on exercise capacity. Secondary outcomes included mortality, hospitalisation, NT-proBNP levels, echocardiographic and hemodynamics parameters and discontinuation rate.Results22 studies were included (n = 5448), including 3, 8 and 11 studies with low, high and unknown risk of bias, respectively. PH-targeted therapies were associated with an improvement of exercise capacity (standardized mean difference 0.29;95%CI:0.08–0.50, p = 0.006). Pre-specified subgroup analyses found that this improvement was predominantly observed in studies evaluating phosphodiesterase-5 inhibitors and prostanoids and in patients with reduced ejection fraction. Moreover, systolic pulmonary artery pressure measured by echocardiography was improved (mean difference: -7.5mmHg; [95%CI]: -14.9,-0.1, p = 0.05), which was also entirely driven by studies evaluating phosphodiesterase-5 inhibitors. However, PH-targeted therapies were associated with an increased treatment discontinuation rates and a potential increase in mortality compared to standard treatment.ConclusionsIn conclusion, PH-targeted therapies and especially phosphodiesterase-5 inhibitors may improve exercise capacity in patients with HF. However, an increase in adverse outcomes was likely. Moreover, most studies were at high or unknown risk of bias, precluding confident conclusions about the effects of PH-targeted therapies.

Targeted therapy with phosphodiesterase 5 inhibitors in patients with pulmonary hypertension due to heart failure and elevated pulmonary vascular resistance: a systematic review

“…An exploratory analysis suggested PDE5i may be associated with a decrease in cardiac hospitalizations in some patients with HF but not in patients with valvular disease. 29 These findings are consistent with our study despite differences in patient population (echo diagnosis of PH and inclusion of VHD with no mention of PVR in their SR). The authors also reported a significant increase in treatment discontinuation, with no mention in the subgroup population taking PDE5i.…”

Therapeutic Challenges and Emerging Treatment Targets for Pulmonary Hypertension in Left Heart Disease

“… 87 A meta‐analysis pooling the results of multiple PH‐targeted therapies such as PDE5 inhibitors, prostanoids, ERAs, and soluble guanylate cyclase stimulators has concluded that PDE5 inhibitors may improve exercise capacity in patients with LHD, but that all drug classes resulted in a higher risk for adverse events. 88 …”

Pulmonary Hypertension Complicating Pregnancy

“…In a small minority of IPAH patients who are deemed vasoreactive based on a positive acute vasodilator challenge and without severe RV dysfunction, calcium channel blockers are appropriate and safe to use in pregnancy [3•]. Importantly, PAH-targeted agents have not been shown to be of benefit and can be detrimental in PH due to left heart disease [69]. Therapy in this group should be directed toward optimization of left heart function.…”