Relation between sulfonylurea therapy, complications, and outcome for elderly patients with acute myocardial infarction☆,☆☆,★,★★

Sulfonylureas are the most commonly used second-line drug class for treating type 2 diabetes mellitus (T2DM). While the cardiovascular safety of sulfonylureas has been examined in several trials and nonrandomized studies, little is known of their specific effects on sudden cardiac arrest (SCA) and related serious arrhythmic outcomes. This knowledge gap is striking, because persons with DM are at increased risk of SCA. In this review, we explore the influence of sulfonylureas on the risk of serious arrhythmias, with specific foci on ischemic preconditioning, cardiac excitability, and serious hypoglycemia as putative mechanisms. Elucidating the relationship between individual sulfonylureas and serious arrhythmias is critical, especially as the diabetes epidemic intensifies and SCA incidence increases in persons with diabetes.

Type 2 diabetes has long been recognized as an independent risk factor for cardiovascular disease (CVD), including coronary artery disease (CAD), stroke, peripheral arterial disease, cardiomyopathy, and congestive heart failure. Cardiovascular (CV) complications are the leading cause of comorbidity and death in the patient with diabetes. Vascular complications of diabetes also extend to microvascular disease, manifest as diabetic nephropathy, neuropathy, and retinopathy. The impact of glycemic control in reducing microvascular complications is well established. Although more controversial, there is also evidence that glycemic control can limit macrovascular disease, including CAD, peripheral arterial disease, and stroke. Glycemic control in the context of type 2 diabetes, as well as prediabetes, is also intertwined with CV risk factors such as obesity, hypertriglyceridemia, and blood pressure control. Similarly, major issues and concerns have arisen around the CV safety of antidiabetic therapy. Together, these issues have focused attention on the need to understand the CV effects of current treatments for type 2 diabetes and the optimal strategies for care of patients with this disease.

To examine possible adverse effects of sulfonylureas on survival among patients with diabetes mellitus (DM) who experience a myocardial infarction (MI).

Residents of Olmsted County, Minnesota, with an MI that met standardized criteria from January 1, 1985, through December 31, 2002, were followed up for mortality.

Among 2189 patients with MI (mean ± SD age, 68±14 years; 1237 men [57%]), 409 (19%) had DM. The 23 patients treated with first-generation sulfonylureas, biguanides, or thiazolidinediones were excluded from analyses. Among the remaining 386 patients with DM, 120 (31%) were taking second-generation sulfonylureas, 180 (47%) were taking insulin, and 86 (22%) were receiving nonpharmacological treatment. Patients with DM treated with second-generation sulfonylureas were more likely to be men and have higher creatinine clearance than those treated with insulin. After adjusting for age, sex, Killip class, duration of DM, creatinine clearance, and reperfusion therapy or revascularization, patients treated with second-generation sulfonylureas had a lower risk of death than did diabetic patients receiving insulin (hazard ratio, 0.41; 95% confidence interval, 0.21-0.80; P=.009).

These population-based data do not support the concern about an adverse effect of second-generation sulfonylureas on survival after MI and underscore the importance of population-based studies of surveillance of drug safety.

Las sulfonilureas (SU) son fármacos insulinosecretores que actúan en receptores específicos de la célula beta pancreática. Si bien la monoterapia oral inicial de la diabetes mellitus tipo 2 debe centrarse en el uso de metformina, podemos afirmar que las SU siguen siendo fármacos eficaces en su tratamiento, siempre que se utilicen precozmente cuando aún existe función de la célula beta y, fundamentalmente, en terapia combinada con otros fármacos orales (metformina, glitazonas). Las SU no protegen el deterioro progresivo de la célula beta y, por lo que se refiere a efectos secundarios, es evidente la propensión a la hipoglucemia y al aumento de peso. En cuanto a un posible papel específico favorecedor de la morbimortalidad cardiovascular, hasta el momento no se dispone de datos concluyentes que lo corroboren.

Sulfonylureas are insulin-secreting drugs that act on specific pancreatic beta-cell receptors. Although initial monotherapy of type 2 diabetes mellitus should focus on the use of metformin, sulfonylureas continue to be effective in the treatment of this disease, provided they are used early when there is still some beta-cell function and, especially, in combination with other oral drugs (metformin, glitazones). Sulfonylureas do not protect against progressive beta-cell deterioration. Adverse effects consist of a tendency to produce hypoglycemia and weight gain. To date, there are no conclusive data to support a possible deleterious effect on cardiovascular morbidity and mortality.

The ATP-sensitive potassium (K_ATP) channel is a distinct type of potassium ion channel that is found in the vascular smooth muscle cells of a variety of mammalian species, including humans. The activity of K_ATP channels is determined by many factors including cellular ATP and ADP levels, thus providing a link between cellular metabolism and vascular tone through its effects on membrane potential. Experimental studies using inhibitors of K_ATP channels, such as the sulfonuylurea class of drugs, indicate that these channels modulate coronary vascular tone including the hyperaemia induced by increased myocardial metabolism. This review examines the evidence linking K_ATP channels to the regulation of coronary vascular tone and the potential clinical implications of pharmacologic therapies that act on K_ATP channels.

Diabetes mellitus and heart failure (HF), both of which are associated with high rates of adverse cardiovascular outcomes, commonly coexist. Given the marked increases in diabetes prevalence in developed countries, the proportion of the population with both conditions is likely to increase substantially. This article reviews the epidemiology of HF and diabetes, the mechanisms whereby diabetes causes HF, and the pharmacotherapy of both HF and diabetes. Specific challenges in treating patients with both HF and diabetes are also addressed.