We thank Dr. Jorde for his letter, although we take issue with several points. We disagree that our study was "no more than hypothesis-generating" because of its design and limitations. Pharmacoepidemiologic studies allow the assessment of the effect of medications in real-life situations, in contrast to the highly selected samples of clinical trials. However, they are prone to biases because of confounding by indication. State-of-the-art statistical analyses can compensate for these limitations. Since it is unlikely that ACE inhibitors will ever be compared head-to-head in a clinical trial, our findings should alert physicians that all ACE inhibitors do not offer the same level of benefit after myocardial infarction.

Dr. Jorde, and Drs. Hennessy and Kimmel in their editorial (1), mentions that the risk reductions associated with ramipril versus other ACE inhibitors in our study were large compared with those of ramipril versus placebo. Such a comparison is not entirely appropriate because patients across studies have different risks for death and because it completely ignores the 95% CIs. Any value inside a 95% CI should be considered consistent with the data. All of the 95% CIs for the risk reduction seen with ramipril versus other drugs in our study do overlap with the 95% CIs for ramipril versus placebo in the Heart Outcomes Prevention Evaluation (HOPE) (2) and the Acute Infarction Ramipril Efficacy (AIRE) trial (3). Accordingly, to argue that we reported higher risk reductions between ACE inhibitors than between ramipril and placebo would amount to ignoring the role of sampling error.

The editorial by Drs. Hennessy and Kimmel also suggested that our results might have been confounded by the severity of CHF, even if we did adjust for the presence or absence of any CHF at baseline (1). Fortunately, we were able to empirically test Drs. Hennessy and Kimmel's conjecture. It posits that by pure logic the impact of CHF on mortality would have to be much weaker in the ramipril group than among users of other ACE inhibitors, implying the CHF-by-drugs interactions. We added 6 such interactions to the multivariable model in our Table 3. All of the interactions were statistically nonsignificant (all P values > 0.18), clearly showing that the observed better survival of ramipril users cannot be due to confounding by the unknown severity of CHF.

Dr. Jorde refers to an unpublished study that investigates outcomes such as endothelial function rather than death. This trial, unlike ours, is not a head-to-head comparison of ACE inhibitors. Similarly, the VALIANT trial (4) did not compare different ACE inhibitors but an ACE inhibitor with an angiotensin II blocker. One should be cautious about generalizing results on intermediate outcomes to mortality and about generalizing a similar effect to all agents blocking the renin–angiotensin system.

Drs. Horton, Jorde, Kimmel, and Hennessy are concerned that the higher rate of use of ß-blockers and statins in the ramipril group could explain the apparent survival advantage associated with ramipril. However, all of these authors overlooked the fact that we did adjust for these differences, as can be seen in our Table 3. The results show that the lower mortality rates in the ramipril group are independent of statins and ß-blockers.