PracticeUpdate Diabetes March 2019

EDITOR’S PICKS 10

Excess Risk of Hospitalization for Heart Failure Among People With Type 2 Diabetes Diabetologia Take-home message • Previous studies have shown an association between heart failure and type 2 diabetes (T2D). Some researchers have hypothe- sized that this relationship is causal; therefore, improved glycemic control may improve cardiovascular outcomes in heart failure patients. This study was among the largest ever to assess associations between heart failure and T2D using patient data from the Swedish National Diabetes Register along with data from age-, gender-, and county-matched individuals without diabetes from the population registry. The final dataset contained information from 266,305 individuals with T2D and 1,323,504 matched controls. The results of this study demonstrated that men and women with T2D who were younger than 55 years of age had hazard ratios for hospitalization for heart failure of 2.07 and 4.59, respectively. In addition, younger age (<55 years old), poorer glycemic control, and deteriorating renal function were all associated with increased excess risk of heart failure in those with T2D compared with the control group. Interestingly individuals with T2D who were >75 years old had risk similar to that of matched controls. • This study is important for clinicians to understand because it provides more evidence that T2D is associated with heart failure hospitalizations. This association provides some explanation for why the SGLT2 class of diabetes medications can offer benefits in reducing cardiovascular events, especially heart failure hospitalizations. Jason Sloane MD Abstract

AIMS/HYPOTHESIS Type 2 diabetes is an estab- lished risk factor for heart failure, but age-specific data are sparse. We aimed to determine excess risk of heart failure, based on age, glycaemic control and kidney function in comparison with COMMENT By Kenneth W. Mahaffey MD T he current study is a large obser- vational study of over 250,000 individuals with diabetes and over 1 million controls from Sweden from a national data repository. Diabetes was associated with a significantly increased risk of heart failure, with important obser- vations about subgroups of patients at even higher risk than others, including younger patients with poor glycemic control. These data are quite relevant and timely given the recent revelation of marked improvements in heart failure hospitalizations in patients with type 2 diabetes at increased risk for cardiovas- cular outcomes studied in the published EMPA-REG and CANAVAS programs. 1-3 Marked ~ 40% reductions in hospitaliza- tion for heart failure were observed with SGLT2 inhibitors in the two trials, includ- ing subgroups with or without prior heart failure and in patients with and without known coronary artery disease. The precise mechanism(s) of benefit with these agents is unclear. Leveraging data from large observational registries like

age- and sex-matched control individuals from the general population. METHODS Individuals with type 2 diabetes regis- tered in the Swedish National Diabetes Registry 1998-2012 (n = 266,305) were compared with

age-, sex- and county-matched control individu- als without diabetes (n=1,323,504), and followed over a median of 5.6 years until 31 December 2013. RESULTS We identified 266,305 individuals with type 2 diabetes (mean age 62.0 years, 45.3% women) and 1,323,504 control individuals. Of the individuals with type 2 diabetes and control individuals, 18,715 (7.0%) and 50,157 (3.8%) were hospitalised with a diagnosis of heart failure, respectively. Comparing individuals with diabe- tes with those in the control group, men and women with type 2 diabetes who were younger than 55 years of age had HRs for hospitalisa- tion for heart failure of 2.07 (95% CI 1.73, 2.48) and 4.59 (95% CI 3.50, 6.02), respectively, using analyses adjusted for socioeconomic variables and associated conditions. Younger age, poorer glycaemic control and deteriorating renal func- tion were all associated with increased excess risk of heart failure in those with type 2 diabe- tes compared with the control group. However, people with diabetes who were ≥75 years and without albuminuria or with good glycaemic con- trol (HbA1c ≤52 mmol/mol [≤6.9%]) had a similar risk of hospitalisation for heart failure as control individuals in the same age group. CONCLUSIONS/INTERPRETATION Men and women aged <55 years with type 2 diabetes are at markedly elevated excess risk of heart failure. The excess risk declined with age, but persisted even with good glycaemic control. However, among those who were 75 years and older, dia- betic individuals with well controlled glucose levels or without albuminuria had a risk of heart failure that was on a par with individuals with- out diabetes. Excess Risk of Hospitalisation for Heart Fail- ure Among People With Type 2 Diabetes. Diabetologia 2018 Nov 01;61(11)2300-2309, A Rosengren, J Edqvist, A Rawshani, et al. www.practiceupdate.com/c/75570

that presented by Rosengren and col- leagues in combination with data from rigorous clinical trials is needed to better understand the heart failure risk, iden- tify groups at greatest risk, and promote better understanding of mechanisms and treatment options. References 1. NealB,PerkovicV,MahaffeyKW,etal.Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377(7):644-657. 2. Mahaffey KW, Neal B, Perkovic V, et al. Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS program (Canagliflozin Cardiovascular Assessment Study). Circulation 2017;137(4):323-334. 3. Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2016;374(11):1094.

Dr. Mahaffey is a Professor at Stanford University School of Medicine, Vice Chair of Clinical Research in the Department of Medicine and Director at the Stanford Center for Clinical Research (SCCR) in Stanford, California.

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