Captopril and furosemide prevent hemodynamic tolerance to IV nitrates and improve angina control in patients with unstable angina

Prolonged Intravenous (IV) administration of nitrates is limited by the development of tolerance during the first 24 hours. Angiotensin converting enzyme inhibitors (ACEi) and possibly diuretics may prevent nitrates tolerance. Methods: 30 normotensive unstable angina (UA) patients who were treated by continuous IV isosorbid-dinitrate (ISDN) were randomized to receive either IV ISDN alone (group A, n=15) or IV ISDN with increasing doses of captopril (up to 75 mg/day and low dose furosemide (40 mg/day) (group B, n=15). Nitrates tolerance was evaluated by measuring the total dose of IV ISDN required to decrease MAP by 10% below baseline level. Results: During 60 hours of treatment the test dose of ISDN required to decrease MAP by >10% in group A increased by 206±244% compared to 40±25% in group B (p=0.032). Adverse cardiac events (repeated angina, need for angiography or myocardial infarction occurred in 5 Patients of group A compared to none in group B (p=0.042). Conclusion: Concomitant administration of increasing doses of the ACEi captopril and low dose furosemide with IV ISDN during the first 60 hours of treatment of UA patients decreases nitrates tolerance and improves angina control.