Primary Prevention of Heart Failure in Patients With Type 2 Diabetes Mellitus

Abstract

I n 2008, the US Food and Drug Administration issued an industry guidance that all new therapies for type 2 diabetes mellitus (T2DM) undergo rigorous assessment of cardiovascular safety through large-scale cardiovascular outcome trials (CVOTs) reporting major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, and nonfatal stroke. Although heart failure (HF) was not specifically mentioned in the Food and Drug Administration regulatory guidance and relegated to a secondary outcome, multiple CVOTs have shown various glucose-lowering therapies to variably increase or decrease the risk of HF events. In the case of the sodium-glucose cotransporter 2 (SGLT-2) inhibitors, positive results on HF outcomes have sparked enthusiasm for these agents as a potential HF therapy, and multiple large-scale clinical trials are underway testing these medications in HF populations , irrespective of T2DM status. However, the vast majority of patients in CVOTs of SGLT-2 inhibitors did not have HF at baseline. It is therefore important to recognize that, by impressive reductions in HF events, these randomized trials provide strong evidence for the primary prevention of new-onset HF among patients with T2DM. Among patients with T2DM, HF is the second most common initial presentation of cardiovascular disease after peripheral artery disease, and more frequent than other atherosclerotic complications like myocardial infarction and stroke. A recent large observational study of >270 000 patients with T2DM suggests that optimal management of cardiovascular risk factors may neutralize excess risk of myocar-dial infarction and stroke; but such a relationship was not seen with respect to HF, where even patients with T2DM and no additional risk factors faced a 45% excess risk of HF hospitalization in comparison with individuals without T2DM. 1 Overall risk for mortality after HF diagnosis remains ≈50% at 5 years, a risk worse than many forms of cancer. These data emphasize the prevention of HF as an important unmet need requiring evidence-based strategies. management guidelines issued a class IIA recommendation for using natriuretic peptide screening for those at risk of developing HF, followed by team-based care to prevent the development of new-onset HF. 2 These recommendations were based on 2 trials (Table). 2 In aggregate, these programs enrolled 1674 patients without baseline HF and captured a total of 29 subsequent HF hospitalization events. 2