Comparative effectiveness of angiotensin-receptor blockers for preventing macrovascular disease in patients with diabetes: a population-based cohort study

Abstract

Background: Telmisartan, unlike other angiotensin-receptor blockers, is a partial agonist of peroxisome proliferator-activated receptor-γ, a property that has been associated with improvements in surrogate markers of cardiovascular health in small trials involving patients with diabetes. However, whether this property translates into a reduced risk of cardiovascular events and death in these patients is unknown. We sought to explore the risk of myocardial infarction, stroke and heart failure in patients with diabetes who were taking telmisartan relative to the risk of these events occurring in patients taking other angiotensin-receptor blockers.

Methods: We conducted a population-based, retrospective cohort study of Ontario residents with diabetes aged 66 years and older who started treatment with candesartan, irbesartan, losartan, telmisartan or valsartan between Apr. 1, 2001, and Mar. 31, 2011. Our primary outcome was a composite of admission to hospital for acute myocardial infarction, stroke or heart failure. We examined each outcome individually in secondary analyses, in addition to all-cause mortality.

Results: We identified 54,186 patients with diabetes who started taking an angiotensin-receptor blocker during the study period. After multivariable adjustment, patients who took either telmisartan (adjusted hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.74-0.97) or valsartan (adjusted HR 0.86, 95% CI 0.77-0.95) had a lower risk of the composite outcome compared with patients who took irbesartan. In contrast, no significant difference in risk was seen between other angiotensin-receptor blockers and irbesartan. In secondary analyses, we found a reduced risk of admission to hospital for heart failure with telmisartan compared with irbesartan (adjusted HR 0.79, 95% CI 0.66-0.96), but no significant differences in risk were seen between angiotensin-receptor blockers in our other secondary analyses.

Interpretation: Compared with other angiotensin-receptor blockers, telmisartan and valsartan were both associated with a lower risk of admission to hospital for acute myocardial infarction, stroke or heart failure among older adults with diabetes and hypertension. Telmisartan and valsartan may therefore be the preferred angiotensin-receptor blockers for use in these patients.

Figure 1:

Risk of the composite outcome (admission to hospital for heart failure, acute myocardial infarction or stroke), by angiotensin-receptor blocker used among older adult patients with diabetes. Ratios were adjusted for all variables listed in Appendix 2 (available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.121771/-/DC1). CI = confidence interval, HR = hazard ratio, ref = reference.

Figure 2:

Risk of individual outcomes (death, or admission to hospital for heart failure, acute myocardial infarction, or stroke), by angiotensin-receptor blockers used among older adult patients with diabetes. Ratios were adjusted for all variables listed in Appendix 2 (available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.121771/-/DC1). CI = confidence interval, HR = hazard ratio, ref = reference, TIA = transient ischemic attack.