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Early promise for gene therapy in refractory angina

Early promise for gene therapy in refractory angina

Publication date: Tuesday, 03 October 2017
Contributor(s): Jeremy Bray

In the first study of its kind, gene therapy has been found to be feasible and well tolerated in patients with refractory angina (RA). Treated patients showed increased myocardial perfusion at 1 year in the areas that had impaired myocardial perfusion reserve (MPR) at baseline.

This randomized, blinded, controlled phase I/IIa trial assessed the safety and feasibility of targeted intramyocardial gene therapy in 30 RA patients using adenoviruses expressing human VEGF-DΔNΔC, a new member of the VEGF family that stimulates both angiogenesis and lymphangiogenesis. The study used PET perfusion imaging and an electromechanical catheter system for gene transfer to identify ischaemic, hibernating myocardium with the lowest perfusion reserve for the targeted therapy.

MPR increased significantly in the treated area in the treatment group compared with baseline (1.00 ± 0.36) at 3 months (1.31 ± 0.46, P = 0.045) and 12 months (1.44 ± 0.48, P = 0.009) whereas it tended to decrease in the reference area. MPR in the control group showed no significant change from baseline to 3 and 12 months (1.26 ± 0.37, 1.57 ± 0.55, and 1.48 ± 0.48; respectively, P = 0.690). Treated patients in the highest Lp(a) tertile at baseline showed the best response to therapy (MPR 0.94 ± 0.32 and 1.76 ± 0.41 baseline and 12 months, respectively, P = 0.023).

In spite of improved medical and revascularization therapies, 5–10% of patients undergoing coronary angiography have refractory angina, meaning that they are severely symptomatic while on optimal medical therapy and are not amenable to further revascularization procedures. In the EU and USA, there are >200,000 new RA patients/year suggesting an unmet clinical need for new therapies. Some patients with coronary artery disease develop collateral arteries, which can rescue ischaemic myocardium in spite of significant occlusions in coronary arteries and alleviate ischaemic symptoms. Therapeutic vascular growth stimulates this natural process and offers a potential new treatment for RA.


The study provides the first evidence of the efficacy and safety of targeted gene therapy in patients with refractory angina. Further trials are now needed to confirm these findings. In addition, plasma Lp(a) may be a potential biomarker to identify patients that may have the greatest benefit with this therapy.

Hartikainen J, et al. Adenoviral intramyocardial VEGF-DΔNΔC gene transfer increases myocardial perfusion reserve in refractory angina patients: a phase I/IIa study with 1-year follow-up. European Heart Journal 2017;38:2547-55.
Topics covered:
Category: Evidence in Practice
Edition: Volume 2 Number 9 PCCJ Online 2017
Contributor(s): Jeremy Bray

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