Research updates

Presented by Dr. John Swiston, MD, FRCPC, VGH Pulmonary Hypertension Clinic, Vancouver, BC

Background. A patient registry, such as CPHR, is an organized system to collect data on a specific group of patients and serves as a vital tool for clinical research. CPHR could help PHA Canada and the Canadian PH community better understand the nature of Canadian PH patients by finding out who is getting diagnosed, where they are in the country, and their treatment regimes, as well as capturing important real-world data on patients’ clinical status and outcomes.

Current status. CPHR already has data from more than 2,000 Canadian PH patients. These are largely WHO group 1 PAH and group 4 CTEPH patients from 13 Expert PH Centres, including 11 adult and two pediatric centres. 68% of enrolled PH patients are female, and most patients are aged 50 – 75. CPHR already supports
Canadian PH research, including the publication of three research articles and six abstracts, and five ongoing studies using CPHR data. Most of these studies involve collaborative work across several Expert PH Centres. CPHR also permits Canadian PH researchers to collaborate globally, for example, through «PHederation,» a public-private partnership for PH scientific collaboration across a network of realworld data sources such as CPHR. CPHR also facilitates new projects and partnerships with corporate sponsors, which brings more research support.

Future. Funding from PHA Canada will support active efforts to capture data from patients in all 22 Canadian Expert PH Centres.

Presented by Dr. Marc de Perrot, MD, MSc, FRCSC, UHN CTEPH Program, Toronto, ON

Background. CTEPH is a common and important cause of PH which develops following recurrent or multiple pulmonary emboli (=blood clots in the lungs). CTEPH must be diagnosed— based on clear Canadian clinical practice guidelines—to provide patients with effective therapies, including potentially a complete cure of CTEPH using surgical pulmonary endarterectomy (PEA).

Current status. Since 2005, the UHN CTEPH Program in Toronto has performed PEA in more than 500 CTEPH patients, ranging in age from 3 – 89. PEA significantly improves the severity of PH and right-ventricular (RV) heart failure, and clinical benefits include fewer symptoms and functional limitations, a better quality of life, and markedly improved survival (e.g., 87% after five years; 79% after ten years). PEA is a major surgery, with an
overall risk of death of 2.5 % and a higher risk in CTEPH patients with more severe PH and RV failure. PEA is most effective in CTEPH patients with larger blood clots in the main pulmonary arteries. PEA also benefits CTEPH patients with smaller clots, who are most often female; these patients may need PH-targeted medications before PEA and are two times more likely to need PH-targeted medications for persistent CTEPH following PEA.

Future. An increasing number of Canadian CTEPH patients are eligible for the dramatic benefits of PEA surgery, including a potential cure. However, some CTEPH patients with more severe PH and RV failure, or smaller blood clots, should be considered for PH-targeted medications before or after PEA, and possibly alternative
therapies, such as Balloon Pulmonary Angioplasty (BPA) to open plugged pulmonary artery branches. 

Presented by Dr. Sanjay Mehta, MDCM, FRCPC, Southwest Ontario PH Clinic, London, ON

Background. Over more than 25 years of research and drug development, ten different PH-targeted medications have become available in Canada. Many Canadians living with PH have benefitted with fewer symptoms and limitations, better quality of life, and longer survival. Yet, many PH patients remain very ill and need new therapies. The current medications target three pathways in PAH: the prostanoid, endothelin, and nitric oxide (NO).

Current status. Active research has identified other key scientific abnormalities in PAH, which are now being targeted in human clinical trials. For example, the thickening and blockages of the blood vessels in the lungs (=pulmonary arteries) are due to the uncontrolled growth of smooth muscle cells and endothelial cells. Many chemicals in the body stimulate the growth of cells and can be targeted by medications. The drug sotatercept, injected under the skin (=subcutaneously), soaks up some of these chemicals (GDFs, activins) and improves many aspects of PAH, possibly reducing cell growth. There are many other exciting new therapies in current clinical studies, including kinase inhibitors (inhaled seralutinib and imatinib) and several Canadian-developed potential therapies, including olaparib (PARP-1 inhibitor), apabetalone (BRD4 inhibitor), intravenously injected gene-enhanced endothelial stem cells.

Future. Ongoing research is already developing new therapies, and we expect many more advances in PH treatment over the next five years, helping us further improve the lives of all Canadians living with PH.