Withdrawal of long-term quinapril after experimental myocardial infarction in rats caused progressive left ventricular hypertrophy, endothelial dysfunction, and a 24% rate of heart failure signs.
RCT
Randomized to sacrifice at 0, 4, and 6 weeks
Does withdrawal of long-term ACE inhibition lead to adverse hemodynamic, neurohormonal, and vascular consequences in a rat model of myocardial infarction?
Abrupt discontinuation of long-term ACE inhibition post-MI in an experimental model leads to rapid neurohormonal activation, endothelial dysfunction, and progressive left ventricular hypertrophy.
BACKGROUND: Although discontinuation of chronic ACE inhibitor (ACEi) therapy after myocardial infarction (MI) is common in clinical practice, some clinical studies reported an increased incidence of ischemia-related events after withdrawal. To further address this issue, we assessed hemodynamic, neurohormonal and vascular consequences of withdrawing long-term ACEi treatment after experimental MI. METHODS: Rats were subjected to coronary ligation to induce MI, and received quinapril (15 mg/kg/day) from 2 weeks to 14 months post-MI. Subsequently, surviving rats were randomized to sacrifice at 0, 4, and 6 weeks after ACEi withdrawal. Rats were studied for signs of heart failure, hemodynamics and cardiac function, neurohormones, and vascular edothelial function. RESULTS: After discontinuation of ACEi treatment, plasma aldosterone levels increased between 0-4 weeks without further increment thereafter, suggesting persistent RAAS activation. Acetylcholine-induced aortic relaxation was impaired at 4 and 6 weeks, indicating rapid and sustained development of endothelial vasodilator dysfunction after withdrawal. Moreover, 24% of the rats developed heart failure signs (edema, dyspnea), and 3 rats died, all within 4 weeks after withdrawal. Significantly increased N-ANP levels and lung weights at 4, but not at 6 weeks suggest a transient volume overload. Finally, LV/body weight ratios significantly increased between 0-4 as well as 4-6 weeks, indicating progressive LV hypertrophy. CONCLUSIONS: The observed alterations after withdrawing long-term post-MI quinapril treatment in the present study may account for an increased risk for ischemic events. Thus, our findings highlight the potentially harmful effects associated with abrupt discontinuation of long-term post-MI ACE inhibition, and imply careful clinical consideration in this matter.
Westendorp et al. (Sat,) conducted a rct in Myocardial Infarction. ACE inhibitor (quinapril) withdrawal vs. Baseline (0 weeks after withdrawal) was evaluated on Hemodynamic, neurohormonal and vascular consequences. Withdrawal of long-term quinapril after experimental myocardial infarction in rats caused progressive left ventricular hypertrophy, endothelial dysfunction, and a 24% rate of heart failure signs.