Combo Improves Blood Flow in Pulmonary Arterial Hypertension - Medscape

Posted: 28 Oct 2019 12:00 AM PDT

For patients with newly diagnosed pulmonary arterial hypertension, the combination of macitentan (Opsumit, Actelion Pharmaceuticals) plus tadalafil (Adcirca, Eli Lilly) improves hemodynamics, function, and risk profile, results from the OPTIMA study show.

"This is another demonstration that initial combination therapy is particularly efficacious in patients with PAH," said Olivier Sitbon, MD, PhD, from Université Paris–Sud.

"Combination therapy is becoming the treatment of choice for the vast majority of patients with PAH; here we have another option," he reported at CHEST 2019 in New Orleans.

Results from the 2015 AMBITION study showed that the combination of ambrisentan (Letairis, Gilead Sciences), an endothelin-receptor antagonist, plus tadalafil, a phosphodiesterase type-5 inhibitor, was more effective than monotherapy.

"So we know for the long term, initial combination therapy is efficacious and results in a delay of progression, compared with monotherapy," Sitbon said. In fact, the AMBITION findings led to the approval of the combination of ambrisentan and tadalafil for patients with pulmonary arterial hypertension, as reported by Medscape Medical News.

"But we didn't get any hemodynamic results from that study," he said.

OPTIMA is the first study to show hemodynamic results for combination therapy, he told Medscape Medical News. "Until now, we've had very little information."

With macitentan and tadalafil, "we observed a major hemodynamic improvement," with a decrease in pulmonary muscular resistance of almost 50% and a reduction in pulmonary vascular remodeling of 47%, said Sitbon.

"There was also improvement in cardiac output, a decrease in pulmonary artery pressure, and a major decrease — of about 70% — in the level of NT-proBNP, which is a very important biomarker for disease severity."

"We know it's good news when patients reach a normal level of NT-proBNP," he added.

OPTIMA Trial

The 46 participants in the OPTIMA trial — which was sponsored by Actelion Pharmaceuticals — had been diagnosed with pulmonary arterial hypertension in the previous 6 months, and all were treatment-naïve. All had a WHO functional classification of II or III and a 6-minute walk distance of less than 50 meters (164 feet).

In the study cohort, the condition was idiopathic, heritable, drug- or toxin-induced, associated with connective tissue disease, or associated with HIV infection. Two participants — one with suspected pulmonary veno-occlusive disease who saw no benefit from the drug combination and withdrew from the study and another whose diagnosis was reclassified as coronary heart disease — were excluded from the analysis.

At baseline, right heart catheterization screening showed that mean resting pulmonary arterial pressure was at least 25 mm Hg, pulmonary artery wedge pressure or left ventricular end diastolic pressure was 15 mm Hg or less, and pulmonary vascular remodeling was at least 400 dyne-second per cm⁻⁵ for wedge pressure below 12 mm Hg or at least 500 dyne-second per cm⁻⁵ for wedge pressure from 12 to 15 mm Hg.

There was a 47% reduction in the primary study end point of the ratio of pulmonary vascular remodeling from baseline to 16 weeks (P < .0001). And 87% of the participants had a decrease of at least 30% in that ratio from baseline to week 16.

Mean 6-minute walk distance improved from 352 m (1156 feet) at baseline to 388 m (1273 feet) at week 16 (P = .0008). And median NT-proBNP level decreased from 1456.8 ng/L at baseline to 404.2 ng/L at week 16 (P < .0001).

At week 16, WHO functional classification had not worsened in any study participant, and had improved in 63%. Approximately 70% of participants met the criteria for WHO functional classification I or II at week 16, whereas at baseline, only 22% met the criteria for functional classification II and none met the criteria for functional classification I.

"Our patients clearly improved with this combination," Sitbon reported. "We did not look at quality-of-life indicators, but when you markedly improve hemodynamics and personal capacity, you improve many aspects of daily life."

This is an "encouraging" study, but it "should not be considered an equivalent trial to longer morbidity-driven end-point studies," Victor Test, MD, from Texas Tech University Health Sciences Center in Lubbock, added in a news release.

However, the findings add "strength to the evidence for upfront dual oral therapy," he noted.

CHEST 2019: American College of Chest Physicians Annual Meeting. Presented October 21, 2019.

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Pulmonary Hypertension Awareness Month Highlights Risks, Symptoms - Pulmonary Hypertension News

Posted: 04 Nov 2019 12:00 AM PST

November is Pulmonary Hypertension Awareness Month, and this year, the Pulmonary Hypertension Association (PHA) is highlighting risk factors and symptoms associated with the disease.

PHA's social media campaign, titled "PHaces of Hope," is based on stories from pulmonary hypertension (PH) patients and their caregivers, as well as healthcare team members. From social media efforts to advocacy, the organization is offering a variety of ways to both raise funds and disease awareness.

There are also other events this month, including runs and walks in Dallas; Murfreesboro, Tennessee; Pompano Beach, Florida; and Rochester, New York.

A Facebook Live Chat on Nov. 13 about chronic thromboembolic pulmonary hypertension (CTEPH) will feature a Q&A with expert Peter Hountras, MD, from the UCHealth University of Colorado Hospital.

Throughout the month, PHA will continually add "PHaces of Hope" testimonials to celebrate individuals within the PH community who inspire and empower others. People can submit their stories, along with a photo or short video, at phassociation.org/shareyourhope.

In her story, patient LaKeshia Orr writes: "My hope is that I can help increase awareness for pulmonary hypertension (PH) from a place of strength and optimism. Sure, PH is a rare and serious medical condition with no cure as it stands. However, when you see me, you'll be met with warmth, a smile, optimism and enough hope for the both of us! I want to share my positive attitude and optimistic outlook with everyone I come in contact with."

Nov. 7 is PH Awareness Month Day of Action, a day set aside for advocacy on behalf of the PH community. PHA is urging support for legislation regarding insurance and medication, and will help schedule a phone conversation or visit with a lawmaker or staff. Plus, supporters may join the organization's advocacy network.

"Although treatment options exist to help people with PH, early diagnosis is still a problem for many individuals and that is why awareness of the disease is so critical," Karen A. Fagan, MD, PHA board of trustees chairwoman, said in a press release. "Our campaign targets awareness among those in the medical community as well as patients, since early diagnosis leads to better outcomes."

PHA is the nation's oldest and largest nonprofit patient organization dedicated to the PH community. Pulmonary Hypertension Awareness Month is also supported by Actelion Pharmaceuticals.

For more information about PHA resources and initiatives, please check the association's toolkit, and info about ways to raise funds for research and other efforts.

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Mary M. Chapman began her professional career at United Press International, running both print and broadcast desks. She then became a Michigan correspondent for what is now Bloomberg BNA, where she mainly covered the automotive industry plus legal, tax and regulatory issues. A member of the Automotive Press Association and one of a relatively small number of women on the car beat, Chapman has discussed the automotive industry multiple times of National Public Radio, and in 2014 was selected as an honorary judge at the prestigious Cobble Beach Concours d'Elegance. She has written for numerous national outlets including Time, People, Al-Jazeera America, Fortune, Daily Beast, MSN.com, Newsweek, The Detroit News and Detroit Free Press. The winner of the Society of Professional Journalists award for outstanding reporting, Chapman has had dozens of articles in The New York Times, including two on the coveted front page. She has completed a manuscript about centenarian car enthusiast Margaret Dunning, titled "Belle of the Concours."

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