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Mortality Rates in Elderly Patients Who Take Different Angiotensin-Converting Enzyme Inhibitors after Acute Myocardial Infarction: A Class Effect?

Louise Pilote, MD, MPH, PhD; Michal Abrahamowicz, PhD; Eric Rodrigues, MSc; Mark J. Eisenberg, MD, MPH; and Elham Rahme, PhD
[+] Article and Author Information

From The Montreal General Hospital, Jewish General Hospital, and McGill University, Montreal, Quebec, Canada.


Acknowledgments: The authors thank Hugues Richard and Roxane du Berger for statistical programming.

Grant Support: In part by The Canadian Institutes of Health Research (grant 93834). Dr. Pilote is funded by The Canadian Institutes of Health Research and holds a William Dawson Chair at McGill University. Dr. Abrahamowicz is a James McGill Professor at McGill University. Drs. Eisenberg and Rahme are funded by the Fonds de la Recherche en Santé du Québec (FRSQ).

Potential Financial Conflicts of Interest:Consultancies: E. Rahme (Pfizer, Merck & Co.); Grants received: E. Rahme (Pfizer, Merck & Co.).

Requests for Single Reprints: Louise Pilote, MD, MPH, PhD, Division of Clinical Epidemiology, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada; e-mail, louise.pilote@mcgill.ca.

Current Author Addresses: Drs. Pilote, Abrahamowicz, Rodrigues, and Rahme: Division of Clinical Epidemiology, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.

Dr. Eisenberg: Divisions of Cardiology and Clinical Epidemiology, Jewish General Hospital, Suite A-118, 3755 Côte-Ste-Catherine Road, Montreal, Quebec H3T 1EZ, Canada.

Author Contributions: Conception and design: L. Pilote, M.J. Eisenberg, E. Rahme.

Analysis and interpretation of the data: L. Pilote, M. Abrahamowicz, E. Rodrigues, M.J. Eisenberg, E. Rahme.

Drafting of the article: L. Pilote, M. Abrahamowicz, E. Rodrigues, M.J. Eisenberg.

Critical revision of the article for important intellectual content: L. Pilote, M. Abrahamowicz, M.J. Eisenberg, E. Rahme.

Final approval of the article: L. Pilote, M. Abrahamowicz, E. Rodrigues, M.J. Eisenberg, E. Rahme.

Statistical expertise: L. Pilote, M. Abrahamowicz, M.J. Eisenberg, E. Rahme.

Obtaining of funding: L. Pilote.

Administrative, technical, or logistic support: L. Pilote.

Collection and assembly of data: L. Pilote, E. Rodrigues.


Ann Intern Med. 2004;141(2):102-112. doi:10.7326/0003-4819-141-2-200407200-00008
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Our study suggests that ACE inhibitors do not lead to a similar reduction in mortality in the first year after acute myocardial infarction. We showed that at currently used dosages, enalapril, captopril, fosinopril, quinapril, and lisinopril were all associated with higher mortality than was ramipril in the first year after acute myocardial infarction. The comparisons for lisinopril and ramipril were not statistically significant. Patients who filled prescriptions for perindopril did not have a statistically significant different mortality from users of ramipril.

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Figures

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Figure 1.
Flow diagram.

ACE = angiotensin-converting enzyme; MI = myocardial infarction.

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Figure 2.
Unadjusted Kaplan–Meier curves according to angiotensin-converting enzyme inhibitor prescribed within 30 days of discharge.

 < 0.001 for the log-rank test.

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Figure 3.
Adjusted hazard ratios and 95% CIs for mortality within 1 year of acute myocardial infarction (MI) according to angiotensin-converting enzyme inhibitor prescribed.
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Comments

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Premature advice to patients on ramipril by Annals
Posted on July 28, 2004
Ulrich P. Jorde
New York University School of Medicine
Conflict of Interest: None Declared

Pilote et al. present data on the use of ACE inhibitors (ACEI)post myocardial infarction suggesting superiority of ramipril over other ACEI. The methods are carefully discussed and, in concert with the accompanying outstanding editorial, should confer the overall message that this data by virtue of the study design and limitations is no more than hypothesis generating. The authors rightfully point out that the distribution of observed mortality differences between the seven ACEI studied is not consistent with any known pharmacological property of these agents (i.e. ACEI with higher tissue affinity did not consistently fare better than those with low tissue affinity!). The editorial further notes that mortality differences between ACEI in this analysis are larger than those between ACEI and placebo in randomized, prospective trials (raising significant concerns about validity of this data) as well as substantially higher betablocker and statin use in subjects receiving ramipril. Therefore, the conclusion that "survival benefit seems to differ according to ACEI used" seems somewhat premature, much like the similar content of the "take home message" in the "patient section".

We have recently completed the first randomized, double-blind, prospective study comparing effects of chronic therapy with low versus high tissue affinity ACEI on endothelial function, exercise capacity,and neurohormonal profiles in subjects with CHF and did not detect differences (AJC, in press). In the absence of positive large scale head to head comparison trials of ACEI the available evidence (including the recent VALIANT trial) strongly suggests that no clinically relevant differences exist between agents blocking the renin-angiotensin - a reassuring message to our patients.

Conflict of Interest:

None declared

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Summary for Patients

ACE Inhibitors after Heart Attacks: Varying Effects?

The summary below is from the full report titled “Mortality Rates in Elderly Patients Who Take Different Angiotensin-Converting Enzyme Inhibitors after Acute Myocardial Infarction: A Class Effect?” It is in the 20 July 2004 issue of Annals of Internal Medicine (volume 141, pages 102-112). The authors are L. Pilote, M. Abrahamowicz, E. Rodrigues, M.J. Eisenberg, and E. Rahme.

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