American Journal of Medicine, internal medicine, medicine, health, healthy lifestyles, cancer, heart disease, drugs

Novel and Emerging Therapeutics for Primary Prevention of Cardiovascular Disease

Effect of the SGLT2 inhibitor dapagliflozin on total body weight and systolic blood pressure in patients with type 2 diabetes mellitus on metformin. When added to background metformin therapy, dapagliflozin induced early effects on total body weight (A) and systolic blood pressure (B) that were sustained over 4 years of treatment.43 Copyright © 2015 John Wiley & Sons.

Cardiovascular disease is responsible for 205 deaths per 100,000 persons annually and is the leading cause of death worldwide. The public health burden of cardiovascular disease is expected to continue to grow as the prevalence of many cardiovascular risk factors increases. Several novel classes of glucose-lowering, lipid-lowering, and weight-loss therapeutics have shown mortality benefits in outcomes trials. However, a large proportion of subjects in those trials had established cardiovascular disease, so, as a result, the role of these novel therapeutics in primary cardiovascular prevention is controversial. In this review, we highlight recent advances in the pharmacotherapeutic management of the cardiovascular risk factors of hyperglycemia, dyslipidemia, and obesity. We examine key subgroups within recent cardiovascular outcome trials, weigh the risks and benefits of several novel therapeutics, and provide practical insight into the use of these agents. Our article concludes with a look toward the future and provides the practitioner and scientist with an early view of emerging therapeutics that may play an important role in primary cardiovascular prevention.

Introduction

Cardiovascular disease is the leading cause of death in the United States.1 The public health burden of cardiovascular disease is expected to continue to grow as the prevalence of many cardiovascular risk factors increases.2 Moreover, arterial plaques and coronary artery calcification can be detected in 50% of middle-aged, non-smoking persons with ideal exercise routines, body weight, diet, blood pressure, blood cholesterol, and fasting blood glucose.3 Thus, primary cardiovascular prevention has an important public health role.

Nonpharmacologic therapy should be initiated in patients at risk for cardiovascular disease, including exercise, healthy diet, avoidance of smoking, and maintaining a healthy body weight.4 For patients with risk factors for cardiovascular disease, interventions such as lipid-lowering therapy can prevent clinically overt cardiovascular disease, such as myocardial infarction. In this review, we highlight recent advances in the pharmacotherapeutic management of the cardiovascular risk factors of hyperglycemia, dyslipidemia, and obesity, and focus the discussion on patients without established cardiovascular disease.

Sodium-Glucose Cotransporter-2 Inhibitors

Sodium-glucose cotransporter-2 (SGLT2) is responsible for 90% of proximal renal glucose reabsorption.5 The renal threshold for glucose reabsorption is typically 180 mg/dL in healthy individuals and 240 mg/dL in patients with type 2 diabetes mellitus, in part due to increased SGLT2 expression. Pharmacologic SGLT2 inhibition lowers the renal glucose threshold to 70 mg/dL to 90 mg/dL to enhance glycosuria with minimal risk for hypoglycemia. SGLT2 inhibition reduces glycated hemoglobin (HbA1c) by a mean of 0.5% to 1.0% over 52 weeks. SGLT2 inhibition also promotes favorable effects on nonglycemic cardiovascular risk factors by reducing fat mass, inducing total body weight loss, and lowering blood pressure.6, 7, 8, 9 Importantly, these cardioprotective effects are sustained over the long term (Figure 1).8, 9

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-Leo F. Buckley, PharmD, Salvatore Carbone, PhD, MS, Ahmed Aldemerdash, PharmD, Nayyra Fatani, PharmD, John Fanikos, RPh, MBA

This article originally appeared in the January issue of The American Journal of Medicine.

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