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The "high tissue" ACE inhibitor, perindopril significantly reduces the risk of death, hospitalisation for HF and cardiac remodeling in elderly post MI patients with preserved LV function according to results from the PREAMI (Perindopril Remodeling in Elderly with Acute Myocardial Infarction) study announced today at the European Society of Cardiology (ESC) annual meeting.
PREAMI was designed to evaluate, in patients with AMI aged >65 years and with LV ejection fraction „d40%, the effects of perindopril on combined outcome: death, hospitalisation for HF and heart remodelling considered as a >8% increase in left ventricular end diastolic volume in the 12-month period after MI. One thousand, two hundred and fifty nine elderly patients (mean age 73 years old) from 141 centres in five European countries (including Italy) were included, received 4 mg of perindopril the first month and then 8 mg for the remaining 11 months or placebo in double-blind condition on top of recommended treatment. Patients were randomized from day seven to day 20 (mean 11 days) after AMI well treated by conventional therapies, if their left ventricular function, evaluated by echocardiography, was normal (mean LV ejection fraction: 59%).
Perindopril reduces the combined primary end point of death, hospitalisation for HF and cardiac remodelling by 59% (p<0.001). These results were driven by a highly significant reduction in cardiac remodelling of 64% (p<0.001). Hospitalisation for HF was also reduced by 27% with perindopril (NS) -- no differences in mortality alone were observed but mortality rate after one year of follow-up was quite low despite the age of the patients enrolled (6%).
The beneficial effect of perindopril on remodelling was consistent across all predefined subgroups. "These new results filled the last gap in the information on the effect of ACE inhibitors in post MI patients; PREAMI demonstrates first that in elderly patients surviving MI, correctly treated, and with an extremely normal LV function, cardiac remodelling silently appears; second that an ACEI, perindopril, given at 8 mg per day can totally prevent it!" commented Prof R. Ferrari, chairman of PREAMI.
"These results should have important implications for the management of elderly patients after MI and in good clinical conditions, a population more and more frequently admitted to internal medicine departments where revascularisation or stay in the intensive care unit is not necessarily required," according to Prof L. Tavazzi, co-chairman of the study.
Perindopril was easy to initiate in such a population and very well tolerated at 8 mg per day. These results can be put in the perspective of those of the EUROPA trial previously reported, where perindopril prevented cardiovascular death and MI in coronary artery disease patients regardless of their cardiovascular risk, a high proportion of them having had an MI.
BP decrease and antiatherosclerotic properties (endothelial dysfunction correction, NO increase, antiapoptotic effect) were the main explanations of the beneficial effect of perindopril; it seems now with the PREAMI results that prevention of cardiac remodelling could also be one of the main features of perindopril.