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2017 ; 7
(2
): 312-325
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Combination therapy in pulmonary arterial hypertension: recent accomplishments
and future challenges
#MMPMID28597774
Lajoie AC
; Bonnet S
; Provencher S
Pulm Circ
2017[Apr]; 7
(2
): 312-325
PMID28597774
show ga
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized
by a progressive increase in pulmonary vascular resistance, ultimately leading to
right heart failure and death. Throughout the past 20 years, numerous specific
pharmacologic agents, including phosphodiesterase-5 inhibitors, endothelin
receptor antagonists, prostaglandins, and more recently, soluble guanylate
cyclase stimulators and selective IP prostacyclin receptor agonist, have emerged
for the treatment of PAH. Early clinical trials were typically of short-term
duration, comparing the effects of PAH-targeted therapies versus placebo and
using exercise tolerance as the primary endpoint in most trials. A meta-analysis
of these trials documented a reduction in short-term mortality of ?40% with
monotherapy. More recently, we have witnessed a progressive shift in PAH study
designs using longer event-driven trials comparing the effects of upfront and
sequential combination therapy on clinical worsening that is perceived as a more
clinically relevant outcome measure. Recent meta-analyses also documented that
combination therapy significantly reduced the risk of clinical worsening by ?35%
compared with monotherapy alone. In this review article, we will discuss the
evolution of treatments and clinical trial design in the field of PAH over the
past decades with a special focus on combination therapy and its current role in
the management of PAH. We will also detail unresolved questions regarding the
future of PAH patients' care and the challenges of future clinical trials.
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