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Who should be treated with angiotensin-converting enzyme inhibitors after myocardial infarction?
Insights
Angiotensin-converting enzyme (ACE) inhibitors show a small, uncertain mortality benefit post-myocardial infarction in unselected patients. Selective use in patients with impaired ventricular function demonstrates a clearer, significant mortality benefit.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Angiotensin-converting enzyme (ACE) inhibitors are established treatments for hypertension and heart failure.
- Their role in post-myocardial infarction (MI) care remains a subject of clinical debate.
- Key question: universal early use versus selective administration in post-MI patients.
Purpose of the Study:
- To evaluate the efficacy of ACE inhibitors in reducing mortality after myocardial infarction.
- To compare the outcomes of widespread early use versus selective use in specific patient subgroups.
- To analyze data from large-scale clinical trials addressing ACE inhibitor therapy post-MI.
Main Methods:
- Analysis of data from major clinical trials including Gruppo italiano per lo Studio delta Sopravvlvenza nell' infarcto Miocardico (GISSI-3), Fourth International Study of Infarct Survival (ISIS-4), Survival and Ventricular Enlargement (SAVE), Acute Infarction Ramipril Efficacy (AIRE), and Trandopril Cardiac Evaluation (TRACE).
- Comparison of mortality benefits in unselected patient populations versus those selected based on criteria like impaired ventricular function.
- Assessment of short-term versus long-term outcomes associated with ACE inhibitor use.
Main Results:
- Large trials (GISSI-3, ISIS-4) showed a small, uncertain mortality benefit with early, widespread ACE inhibitor use in unselected post-MI patients.
- Trials with patient selection based on impaired ventricular function (SAVE, AIRE, TRACE) demonstrated a marked and certain mortality benefit with long-term ACE inhibitor prescription.
- Potential dilution of benefit in unselected groups, with some patients possibly experiencing harm.
Conclusions:
- The benefit of ACE inhibitors post-MI appears most significant in selected patients with impaired ventricular function.
- Widespread, early use in all post-MI patients may offer limited and uncertain mortality reduction.
- Further research is ongoing regarding other potential actions of ACE inhibitors, such as MI prevention.
Abstract:
Angiotensin-converting enzyme (ACE) inhibitors are now established drugs in the treatment of hypertension and heart failure. However, their use in patients after a myocardial infarction has occurred remains controversial. The major clinical question regarding ACE inhibitors is whether they should be given to all patients immediately after thrombolysis or whether their use should be restricted to a particular subgroup. This question has now been addressed in several large-scale trials of mortality after myocardial infarction, and no important new information seems likely to emerge on the issue. Clinicians must therefore decide what their practice will be on the basis of data that are currently available. The authors of the recently published Gruppo italiano per lo Studio delta Sopravvlvenza nell' infarcto Miocardico (GISSI-3) and Fourth International Study of Infarct Survival (ISIS-4) mega-trials advocate a policy of widespread and early use of ACE inhibitors in all patients after myocardial infarction occurs. However, the small mortality benefit observed from use of ACE inhibitors in these studies lacks certainly and may prove difficult to reproduce in the general population of patients who have had an infarct outside the setting of a trial. Although patients were essentially not selected apart from the exclusion of those with marked hypotension, the low 6-month and 1-year mortality figures indicate "selection" compared with the typical population of patients who have had a myocardial infarction. Furthermore, a significant long-term mortality benefit was not observed with the short-term (4- to 6-week) use of ACE inhibitors in these trials. In contrast, in the Survival and Ventricular Enlargement (SAVE), Acute Infarction Ramipril Efficacy (AIRE), and Trandopril Cardiac Evaluation (TRACE) trials, where evidence of impairment of ventricular function was used to select patients, both a marked and certain benefit regarding mortality was apparent from long-term prescription of these drugs. Importantly, the marked benefit observed in these selected patients may have been "diluted out" in the larger scale trials of unselected patients where the majority may have gained little and some may have been harmed by treatment or its withdrawal. In most of the large mortality trials the rationale for use of ACE inhibitors after myocardial infarction was stated to be their likely beneficial effect on "remodeling" of the heart after "Infarct expansion." Because adverse remodeling occurs in only a proportion of patients after a heart attack, the benefits of ACE inhibitor therapy might be predicted to be largely limited to this group, which would favor a selective policy. However, strong claims have been made that ACE inhibitors have other important actions, including prevention of myocardial infarction. If this is confirmed in a number of ongoing large-scale trials. then an even ore widespread use of these agents can be expected.