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Vasodilators after myocardial infarction-ISIS IV
1Cardiac Department, John Radcliffe Hospital, Oxford, England.
Insights
Early use of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (MI) patients significantly reduces mortality by 5-10%. Routine early treatment, followed by reassessment, offers the greatest benefit for acute myocardial infarction (MI) management.
Area of Science:
- Cardiology
- Clinical Trials
- Pharmacology
Background:
- Previous small trials suggested high benefits from vasodilators in acute myocardial infarction (MI), but with significant statistical uncertainty.
- The role of early angiotensin-converting enzyme (ACE) inhibitors in acute MI was unclear, with potential risks like hypotension.
- Nitrates were found to be safe but offered no statistically significant mortality reduction when used routinely.
Purpose of the Study:
- To clarify the benefits and risks of early pharmacological interventions in acute myocardial infarction (MI).
- To evaluate the efficacy of nitrates, magnesium, and ACE inhibitors in the early phase of acute MI.
Main Methods:
- Analysis of data from large-scale clinical trials, including GISSI-3 and International Studies of Infarct Survival (ISIS-4).
- Comparison of mortality rates and adverse events associated with different drug classes.
Main Results:
- Routine nitrate use in acute MI showed no statistically significant mortality reduction.
- Magnesium administration in ISIS-4 yielded disappointing results with a slight excess mortality.
- Routine early administration of ACE inhibitors demonstrated a statistically significant 5-10% reduction in mortality, particularly in patients with left ventricular damage.
Conclusions:
- ACE inhibitors are beneficial in the early phase of acute MI, offering significant mortality reduction.
- While nitrates are safe, their routine early use does not provide significant mortality benefits.
- A strategy of initial ACE inhibitor treatment for all acute MI patients, followed by reassessment, is recommended for maximal benefit.
Abstract:
Although small trials had suggested unrealistically high benefits from the use of vasodilators in acute myocardial infarction (MI), there was considerable statistical uncertainty about these benefits. Angiotensin-converting enzyme (ACE) inhibitors are clearly beneficial for left ventricular dysfunction after MI, but it was uncertain whether there was risk (from hypotension) for some patients in the early hours of an MI. After the GISSI-3 and International Studies of Infarct Survival (ISIS-4) trials it is now clear that nitrates are safe, but used routinely the small mortality reduction was not statistically significant. In ISIS-4 the results with magnesium were disappointing, with a worrying small excess mortality. On the other hand, routine use of ACE inhibitors in this early phase showed a statistically significant 5 to 10% reduction in mortality. There was greatest benefit in those with more obvious left ventricular damage. Since it is not easy to identify all such patients in the first hours, a policy of initial treatment of all, then later reassessment, is safe and would produce the greatest overall benefit.