ARBs in Diabetes — Some Good, Some Better!

ARBs in Diabetes — Some Good, Some Better!

Abstract & Commentary

By Rahul Gupta, MD, MPH, FACP

Clinical Assistant Professor, West Virginia University School of Medicine, Charleston, WV

Dr. Gupta reports no financial relationships relevant to this field of study.

Synopsis: Telmisartan and valsartan were both associated with lower risk of hospital admission for macrovascular events in older adults with diabetes and hypertension when compared to other angiotensin-receptor blockers.

Source: Antoniou T, et al. Comparative effectiveness of angiotensin-receptor blockers for preventing macrovascular disease in patients with diabetes: A population-based cohort study. CMAJ 2013;185:1035-1041.

It is estimated that approximately 26 million americans suffer from diabetes, including almost one-third who continue to remain unaware of the disease diagnosis. Almost 2 million people in the United States are diagnosed with diabetes each year. Additionally, with the prevailing obesity epidemic, it is estimated that approximately 79 million more Americans suffer from a condition termed prediabetes. It is anticipated that unless prevented, a significant proportion of these individuals are likely to advance to overt diabetes thereby further raising the economic costs. Diabetes is also an expensive disease. The total costs of diagnosed diabetes in the United States in 2012 were estimated to be $245 billion. This means that after adjusting for population age and sex differences, average medical expenditures among people with diagnosed diabetes are 2.3 times higher than what expenditures would be in the absence of diabetes. Such significant increases in costs relative to other illnesses can be attributable to resultant complications from both macrovascular disease (atherosclerosis) as well as microvascular disease (retinopathy, nephropathy, and neuropathy). The risk of developing such complications as well as disease progression can be reduced with interventions aimed at strategies to achieve multifactorial risk reduction, early screening, and management. Many interventions intended to prevent and control diabetes are very cost-effective and supported by strong evidence.¹ Multifactorial cardiac risk reduction includes blood pressure, lipid and glycemic control, routine use of aspirin (unless contraindicated), smoking cessation, diet, and exercise, as well as the use of an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB).

Although in clinical practice ARBs are often considered to be essentially interchangeable, some evidence from studies suggests that may not be the case. For example, some research from small clinical trials suggests that telmisartan may exhibit slightly different properties than other members of this drug class, and may therefore be superior in cardiovascular health.2

Antoniou et al conducted research to evaluate whether there is a difference in the risk of developing acute myocardial infarction, heart failure, and stroke among older patients with diabetes who are managed with telmisartan, candesartan, irbesartan, losartan, or valsartan. In this population-based, retrospective, cohort study of Ontario residents, data were evaluated for 54,186 patients with diabetes ≥ 66 years who received ARBs between April 1, 2001 and March 31, 2010. The primary outcome was a composite of admission to the hospital for acute myocardial infarction, stroke, or heart failure. Secondary analyses included all-cause mortality as well as evaluating each outcome individually. Among the patients excluded were those taking ACE inhibitors in conjunction with ARBs.

In the main analysis, researchers reported that patients who received 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 significantly lower risk of the primary outcome (i.e., admission to hospital for acute myocardial infarction, stroke, or heart failure) when compared to patients who received irbesartan. In contrast, researchers found no difference in the risk of the primary outcome between irbesartan and other ARBs (losartan or candesartan). In secondary analyses, researchers found a lower risk of admission to the 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 other ARBs. The authors concluded that compared with other ARBs, telmisartan and valsartan were both associated with a lower risk of hospital admission for acute myocardial infarction, stroke, or heart failure among older adults with diabetes and hypertension and, consequently, these may be the preferred ARBs to prescribe in such patients.

COMMENTARY

Compared with non-diabetics, men and women with type 2 diabetes have at least 6-8 years’ decreased life expectancy, and disease-related vascular illnesses are the main causes of death. For a majority of patients, by the time they are diagnosed with type 2 diabetes, one or more risk factors for macrovascular disease such as obesity, dyslipidemia, hypertension, or smoking already exist. A number of patients already have evidence of overt atherosclerosis by the time they are diagnosed with type 2 diabetes. Therefore, it is vital that when clinicians place such patients on a course of multifactor risk-reduction strategy, the best clinical data available are utilized for each pharmacotherapy in order to optimize medical management. This study suggests that there are statistically important differences in the effectiveness of ARBs when used for the prevention of diabetes-related macrovascular diseases. In other words, not all ARBs are the same. Therefore, it is imperative that we do not assume a class effect for these agents when prescribing for this purpose. While this is a retrospective study, this research confirms some of the smaller studies conducted to date as well as reinforces the concept that drugs, such as telmisartan, exhibit several pleoiotropic properties that distinguish it from other members of this drug class. There is also some pharmacological basis to believe this as well, since telmisartan exhibits a partial peroxisome proliferator activator receptor gamma-agonist effect that may favorably impact lipid metabolism and insulin sensitivity. Similarly, valsartan has also been shown to have a cardioprotective effect by inhibiting platelet aggregation, a benefit that may be more pronounced in diabetics.³ My takeaway from this study is that if I had to prescribe an ARB to a diabetic with the intent to reduce the macrovascular complications, I would prefer telmisartan and valsartan over all others.

References

1. Li R, et al. Cost-effectiveness of interventions to prevent and control diabetes mellitus: A systematic review. Diabetes Care 2010;33:1872-1894.
2. Frampton JE. Telmisartan: A review of its use in cardiovascular disease prevention. Drugs 2011;71:651-677.
3. Serebruany VL, et al. Valsartan inhibits platelet activity at different doses in mild to moderate hypertensives: Valsartan Inhibits Platelets (VIP) trial. Am Heart J 2006;151:92-99.