The Coronary ARteriogenesis with combined Heparin and EXercise therapy in chronic refractory Angina (CARHEXA) trial: A double-blind, randomized, placebo-controlled stress echocardiographic study
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Published on: February 3, 2021
Marija T Petrovic1, Ana Djordjevic-Dikic1, Vojislav Giga1
1Cardiology Clinic, Clinical Centre of Serbia, School of Medicine, University of Belgrade, Serbia.
Insights
Heparin plus exercise significantly improved angina symptoms and myocardial ischemia in coronary artery disease patients. This combination therapy enhanced coronary collateral circulation more effectively than exercise alone.
Area of Science:
- Cardiology
- Exercise Physiology
- Pharmacology
Background:
- Coronary collateral circulation protects against myocardial ischemia in coronary artery disease (CAD).
- Exercise can promote collateral formation, but the combined effect with heparin on cardiac function and angina is unclear.
Purpose of the Study:
- To evaluate the anti-ischemic efficacy of combining heparin with exercise in patients with coronary artery disease.
Main Methods:
- A randomized, double-blind study involving 32 'no-option' CAD patients with stable angina.
- Participants underwent a two-week exercise regimen, randomized to receive intravenous unfractionated heparin or placebo before exercise sessions.
- Assessments included Canadian Cardiovascular Society angina class, stress ECG, echo-derived wall motion score index, and computed tomography angiography for collaterals.
Main Results:
- Both groups showed reduced angina class, but only the heparin group improved time to ST-segment depression and wall motion score index.
- Computed tomography angiography revealed improved collaterals in 80% of the heparin group versus 12.5% in the exercise-only group (p<0.001).
Conclusions:
- A two-week regimen of heparin plus exercise is superior to exercise alone for improving angina class, myocardial ischemia, and coronary collateralization in CAD patients.
- This combined approach demonstrates significant anti-ischemic benefits.
Background:
Coronary collateral circulation exerts protective effects on myocardial ischaemia due to coronary artery disease and can be promoted by exercise with heparin co-administration. Whether this arteriogenetic effect is accompanied by functional improvement of left ventricle during stress and lessening of angina symptoms remains unknown.
Aims:
To evaluate the anti-ischaemic efficacy of heparin plus exercise in coronary artery disease.
Methods:
In a prospective, single-centre, randomized, double-blind study we recruited 32 'no-option' patients (27 males; mean age 61 ± 8 years) with stable angina, exercise-induced ischaemia and coronary artery disease not suitable for revascularization. All underwent a two-week cycle of exercise (two exercise sessions per day, five days per week) and were randomized (n = 16 per group) to intravenous placebo (0.9% saline) versus unfractionated heparin (5.000 IU intravenously), 10 min prior to exercise. We assessed Canadian Cardiovascular Society angina class, stress electrocardiogram and echo parameters (wall motion score index) and computed tomography angiography for collaterals.
Results:
After two-week cycle, Canadian Cardiovascular Society class statistically decreased in both groups (heparin plus exercise group: 2.6 ± 0.7 to 1.9 ± 0.7, p < 0.001, exercise group: 2.4 ± 0.7 to 2.1 ± 0.9, p = 0.046). Only the heparin plus exercise group improved time-to-ST segment depression (before 270, 228-327 s vs. after 339, 280-360 s, p = 0.012) and wall motion score index (before 1.38 ± 0.25 vs. after 1.28 ± 0.18, p = 0.005). By multi-slice computed tomography angiography, collaterals improved in 12/15 (80%) in the heparin plus exercise group versus 2/16 (12.5%) in the exercise group (p < 0.001).
Conclusion:
A two-week, 10-test cycle of heparin plus exercise is better than exercise in improving angina class, myocardial ischaemia and collaterals by computed tomography angiography.
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