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. 2005 May 28;330(7502):1269–1270. doi: 10.1136/bmj.330.7502.1269-a

Angiotensin receptor blockers and myocardial infarction

Results reflect different cardiovascular states in patients with types 1 and 2 diabetes

Edmund J Lewis 1; on behalf of the Collaborative Study Group
PMCID: PMC558133  PMID: 15920133

Editor—Verma and Strauss's editorial supports the contention that angiotensin receptor blockers are associated with increased risk of myocardial infarction.1 Included in the documentation of this risk are briefing documents from the US Food and Drug Administration quoting data from the irbesartan diabetic nephropathy trial.2 However, the authors did not cite our published analysis of cardiovascular events during this trial.3 Omitted was any mention that the difference between irbesartan and placebo or amlodipine did not reach significance with respect to myocardial infarctions (P > 0.2 and P = 0.068, respectively). Neither were death rates different.2

A meta-analysis cited in the editorial used faulty logic.4 Its conclusion emphasised that mortality in studies of diabetic nephropathy using angiotensin converting enzyme (ACE) inhibitors was lower than in studies using angiotensin receptor blockers, with the erroneous implication that ACE inhibitors are safer. Most patients in studies using these drugs had type 1 diabetes mellitus, whereas the studies using angiotensin receptor blockers included patients with type 2 diabetes. Our large captopril trial used ACE inhibitors in type 1 diabetic nephropathy.5 All placebo controlled trials that used angiotensin receptor blockers studied type 2 diabetes.

The average age in the captopril trial was 35 and in the irbesartan trial 59. Three per cent of patients in the placebo group and 3.9% in the captopril group (P > 0.3) experienced a myocardial infarction during the course of that study. In the irbesartan trial, these rates were 8% in the placebo and 7% in the irbesartan groups.2 All cause mortality in the placebo group in the irbesartan trial was 16.3% compared with 6.9% in the placebo group in the captopril trial.2,5

The discrepant mortality and rates of non-fatal myocardial infarction for the placebo groups in these two studies are accurate reflections of the marked difference in the cardiovascular status of patients with type 1 and older patients with type 2 diabetes. The implication that difference in these risks could have been explained by the class of renoprotective agent employed is ludicrous.

Competing interests: None declared.

References

  • 1.Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ 2004;329: 1248-9. (27 November.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor blocker irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345: 851-60. [DOI] [PubMed] [Google Scholar]
  • 3.Berl T, Hunsicker LG, Lewis JB, Pfeffer MA, Porush JG, Rouleau J-L, et al. Cardiovascular outcomes in the irbesartan diabetic nephropathy trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 2003;138: 542-9. [DOI] [PubMed] [Google Scholar]
  • 4.Strippoli GFM, Craig M, Deeks JJ, Schena FP, Craig JC. Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systemic review. BMJ 2004;329: 828-38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329: 1456-62. [DOI] [PubMed] [Google Scholar]

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