The aim of the study was to investigate the hemodynamic effects of a short-acting, potent, highly specific calcium antagonist, nisoldipine, in patients with acute myocardial infarction. Twenty-four patients were selected on the basis of an elevated wedge pressure and/or elevated blood pressure, less than 12 hours after the onset of symptoms. Patients were randomized to receive either placebo or low-dose nisoldipine (2 micrograms/kg) as a single intravenous injection over a 3-minute period. hemodynamic effects were monitored for 20 minutes, and thereafter patients were crossed over to the other agent after the preserved parameters had returned to baseline. An open-label study using double the dose of nisoldipine in 20 patients who had not reacted adversely to low-dose nisoldipine followed. Standard hemodynamic monitoring showed that peak effects of nisoldipine were reached at 5 minutes, with some residual effect at 20 minutes, and it took up to 60 minutes to return to baseline. Both doses of nisoldipine had similar effects: a fall in the systemic vascular resistance by about 600 units, variable tachycardia, little or no change in the wedge pressure, a decrease in the arterial pressure, an unchanged rate-pressure product, and an increase in ejection fraction. Tachycardia of more than 15 beats/min resulted in 5 of 24 patients with low-dose nisoldipine and 6 of 20 patients with high-dose nisoldipine. In view of the risk of tachycardia, nisoldipine seems unsuitable for use in the acute phase of myocardial infarction.
SUMMARYThe unique findings from the HOPE (Heart Outcomes Prevention Evaluation) study strongly support extending the use of the angiotensin‐converting enzyme (ACE) inhibitor ramipril as a preventive agent for patients at high risk of cardiovascular events with normal left ventricular function. In addition, ramipril provides significant benefit in diabetic patients. These findings will impact on how ramipril is used in primary care, where ACE inhibitors are currently underprescribed. Patients reflecting the inclusion criteria of the HOPE study should be considered as suitable candidates for long‐term ramipril therapy as an addition to their existing drug regimen. Screening should include control of kidney function (by serum creatinine), particularly within the first two weeks of treatment, in addition to regular monitoring of serum potassium. However, the HOPE study shows that ramipril is well tolerated at high doses and over a long treatment period. The effectiveness of therapy should also be regularly reviewed and dose adjustments made where necessary. If concern remains, referral to a specialist – a cardiologist or a diabetologist – may ultimately be necessary.
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