LISINOPRIL - A REVIEW OF ITS PHARMACOLOGY AND CLINICAL EFFICACY IN ELDERLY PATIENTS

Lisinopril, the lysine analogue of enalaprilat, is a long-acting angio tensin converting enzyme (ACE) inhibitor which is administered once da ily by mouth. The efficacy of lisinopril in reducing blood pressure is well established in younger populations, and many trials now show it to be effective in lowering blood pressure in early patients with hype rtension. In comparative and non-comparative clinical trials, 68.2 to 89.1% of elderly patients responded (diastolic pressure less than or e qual to 90mm Hg) to greater than or equal to 8 weeks' lisinopril treat ment. Age-related differences in antihypertensive efficacy do not appe ar to be clinically significant, and dosages effective in elderly pati ents tend to range from 2.5 to 40 mg/day. Dosages usually need to be l ower in patients with significant renal impairment. In congestive hear t failure, lisinopril 2.5 to 20 mg/day increases exercise duration, im proves left ventricular ejection fraction and has no significant effec t on ventricular ectopic beats. It is similar in efficacy to enalapril and digoxin and similar or superior to captopril on most end-points. Data from the GISSI-3 post-myocardial infarction trial show that lisin opril reduced mortality and left ventricular dysfunction when given fo r 42 days starting within 24 hours of the onset of infarction symptoms . Results at 6 weeks and 6 months were similar in elderly and younger patients. Elderly patients, however, among other subgroups, exhibited a strong reduction in risk of low ejection fraction after treatment (- 25.5%). Economic studies suggest that lisinopril is cost saving compar ed with other ACE inhibitors in some markets. When given according to the GISSI-3 protocol, lisinopril appears to be one of the less experie nce of the successful ACE inhibitor regimens for acute myocardial infa rction. In other trials, patients with diabetic nephropathy and hypert ension improved or did not deteriorate during lisinopril treatment. Bl ood pressure was controlled and reductions or trends towards reduction s in albuminuria were observed. These reductions were similar to those in diltiazem, nifedipine and verapamil recipients, and greater than t hose in patients receiving atenolol. Lisinopril appears to reduce mort ality in diabetic patients after myocardial infarction and may also im prove neuropathy associated with diabetes. Lisinopril is well tolerate d and the profile of adverse events seen is typical of ACE inhibitors as a class. There is a tendency for more elderly than younger patients to discontinue treatment, but this trend is not clearly related to th e incidence of adverse events in these age groups. Drug interactions o ccur with few other agents and are usually clinically significant only between lisinopril and either diuretics or lithium. Lisinopril is, th us, an effective treatment for elderly patients with hypertension, con gestive heart failure and acute myocardial infarction and has shown pr omising benefits in patients with diabetic nephropathy.