LISINOPRIL - A REVIEW OF ITS PHARMACOLOGY AND CLINICAL EFFICACY IN THE EARLY MANAGEMENT OF ACUTE MYOCARDIAL-INFARCTION

Following establishment of its efficacy in hypertension and congestive heart failure, the ACE inhibitor lisinoprii has now been shown to red uce mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment. The ability of lisin opril to attenuate the detrimental effects of left ventricular remodel ling is a key mechanism; however, additional cardioprotective and vasc uloprotective actions are postulated to play a role in mediating the e arly benefit. The GISSI-3 trial in >19 000 patients has demonstrated t hat, when given orally within 24 hours of symptom onset and continued for 6 weeks, lisinopril (with or without nitrates) produces measurable survival benefits with 1 to 2 days of starting treatment. Compared wi th no lisinopril treatment, reductions of 11% in risk of mortality and 7.7% in a combined end-point (death plus severe left ventricular dysf unction) were evident at 6 weeks. Advantages were apparent in all type s of patients. Thus, those at high risk - women, the elderly, patients with diabetes mellitus and those with anterior infarct and/or Killip class >1 - also benefited. These gains in combined end-point events pe rsisted in the longer term, despite treatment withdrawal after 6 weeks in most patients. At 6 months, the incidence rate for the combined en d-point remained lower than with control (a 6.2% reduction). The GISSI -3 results concur with those from recent large investigations (ISIS-4, CCS-1, SMILE) of other ACE inhibitors as early management in myocardi al infarction. However, the results of the CONSENSUS II trial (using i ntravenous enalaprilat then oral enalapril) were unfavourable in some patients. These findings, together with the development of persistent hypotension and, to a lesser extent, renal dysfunction among patients in the GISSI-3 trial, have prompted considerable debate over optimum t reatment strategies. Present opinion generally holds that therapy with lisinopril or other ACE inhibitors shown to be beneficial may be star ted within 24 hours in haemodynamically stable patients with no other contraindications; current labelling in the US and other countries ref lects this position. There is virtually unanimous agreement that such therapy is indicated in high-risk patients, particularly those with le ft ventricular dysfunction. The choice of ACE inhibitor appears less i mportant than the decision to treat; it seems likely that these benefi ts are a class effect. Lisinopril has a tolerability profile resemblin g that of other ACE inhibitors, can be given once daily and may be les s costly than other ACE inhibitors, can be given once daily and may be less costly than other members of its class. However, present cost an alyses are flawed and this latter point remains to be proven in formal cost-effectiveness analyses. In conclusion, early treatment with lisi nopril (within 24 hours of symptom onset) for 6 weeks improves surviva l and reduces cardiovascular morbidity in patients with myocardial inf arction, and confers ongoing benefit after drug withdrawal. While pati ents with symptoms of left ventricular dysfunction are prime candidate s for treatment, all those who are haemodynamically stable with no oth er contraindications are also eligible to receive therapy. Lisinopril and other ACE inhibitors shown to beneficial should therefore be consi dered an integral part of the early management of myocardial infarctio n in suitable patients.