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[Long-term nitrate therapy in coronary heart disease--loss of effect by developing tolerance]
Insights
Long-term oral nitrates, including pentaerythril tetranitrate (PETN) and isosorbide dinitrate (ISDN), effectively treat coronary heart disease with exercise-induced heart insufficiency. Studies show these nitrates reduce pulmonary artery pressure and improve clinical symptoms, countering concerns about nitrate tolerance.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Nitrate tolerance raises questions about the long-term efficacy of nitrates for coronary heart disease (CHD) with exercise-induced heart insufficiency.
- Exercise-induced heart insufficiency is characterized by a pathological increase in pulmonary artery end-diastolic pressure under ergometric load.
Purpose of the Study:
- To evaluate the efficacy of chronic oral nitrate therapy (pentaerythril tetranitrate [PETN] and isosorbide dinitrate [ISDN]) in patients with CHD and exercise-induced heart insufficiency.
- To investigate the potential for nitrate tolerance in this patient group under long-term treatment.
Main Methods:
- A long-term study involving 34 patients with CHD and documented exercise-induced heart insufficiency.
- Assessment of oral nitrate therapy efficacy through clinical and hemodynamic monitoring, including right heart microcatheterization during exertion.
- Dosage titration of PETN and ISDN was employed.
Main Results:
- Oral nitrate therapy led to a significant decrease in pulmonary artery end-diastolic pressure.
- Improvements in pulmonary artery pressure correlated with reduced frequency of anginal attacks, decreased need for sublingual nitroglycerin (GTN), and regression of ST segment depression.
- Right heart microcatheterization during exertion did not reveal clinically significant nitrate tolerance.
Conclusions:
- The study findings argue against clinically remarkable nitrate tolerance in patients with CHD and exercise-induced heart insufficiency receiving long-term oral nitrates.
- Current standard nitrate therapy remains effective for managing coronary heart disease with exercise-induced heart insufficiency.
Abstract:
The therapeutic efficiency of the long-term nitrates in coronary heart disease with exercise-induced heart insufficiency is recently more frequently called in question by observations of a nitrate tolerance. In own long-term studies on 34 patients with coronary heart disease with clinical and haemodynamic evidence (pathologic increase of the end-diastolic pressure of the pulmonary arteries under ergometric load) of an exercise-induced heart insufficiency the efficacy of pentaerythril tetranitrate (PETN) and isosorbide dinitrate (ISDN) in chronic dosage titration use was tested. The oral nitrate therapy evoked a clear decrease of the end-diastolic pressure of the pulmonary arteries. The reduction of the values of the pressure of the pulmonary arteries was correlated with adequate clinical findings (significant decrease of the frequency of pectanginous attacks and of the sublingual need of GTN, regression of the ST segment depression). The own results with particular valuation of the microcatherisation of the right heart on exertion plead against a clinically remarkable nitrate tolerance and confirm the efficiency of the at present usual basic medicamentous therapy in patients with coronary heart disease and exercise-induced heart insufficiency.