Effective pharmacotherapy for the components of the metabolic syndrome is important in improving clinical outcomes. In particular, lowering blood pressure with antihypertensive agents, lowering LDL-C levels with statins, and managing the prothrombotic state with aspirin are well-established methods of reducing the risk of CHD.
1 Although a full review of pharmacologic management of the metabolic syndrome is beyond the scope of the present review, a few general considerations are important.
For the management of hypertension in patients with diabetes mellitus, agents that target the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors (ACEIs), are preferred (or angiotensin receptor blockers when ACEIs are not tolerated).
3 When combination therapy is required, combining an ACEI with a calcium channel blocker is a reasonable choice. This recommendation is based partly on the results of the Avoiding Cardiovascular Events in Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial, in which the combination of benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide for reducing cardiovascular events in patients with diabetes and hypertension.
4
Pharmacotherapy for glycemic control in patients with diabetes is another important component of care and is associated with a decreased risk of diabetes-related complications.
3 Guidelines from the American Diabetes Association recommend the initiation of metformin therapy in combination with TLC at diagnosis and supplementation with additional agents to achieve the target glycosylated hemoglobin level of less than 7% in most patients.
3 These guidelines state that the choice of specific glucose-lowering agents should be individualized for each patient, taking into account the ability of the agent to lower glycosylated hemoglobin, safety and tolerability, ease of use, long-term adherence, cost, and nonglycemic effects.
3 Metformin remains the cornerstone of therapy and is one of the few agents that has been clearly shown to be effective for diabetes prevention.
3,5 Several classes of drugs are associated with weight loss (eg, glucagon-like peptide-1 agonists, pramlintide) or to be weight neutral (metformin, dipeptidyl peptidase-4 inhibitors).
5 In contrast, other agents, such as thiazolidinediones, sulfonylureas, and insulin, are associated with weight gain
5 (
Table 1). In addition, thiazolidinediones are associated with fluid retention, increased risk of congestive heart failure, and possibly myocardial infarction (rosiglitazone).
5
Based on their proven ability to substantially lower LDL-C levels and to reduce the risk of clinical events, statins are the drug of choice for patients with hyperlipidemia. In patients who do not achieve lipid treatment goals with initial statin therapy, there are a number of options (
Table 2). Doubling the dose of the statin produces a modest additional improvement in lipid parameters, but the benefit may not be sufficient to get patients to their goal. Bile acid sequestrants lower LDL-C levels additively in combination with statins and lack systemic toxicity, but they are associated with gastrointestinal symptoms and tend to raise serum triglyceride levels.
1 Niacin produces a favorable effect across the entire lipid profile, raising high-density lipoprotein cholesterol levels and decreasing levels of LDL-C, lipoprotein(a), and triglycerides. However, compliance is a problem because of adverse effects (eg, flushing, gastroin-testinal symptoms).
1 Fibrates are especially effective for lowering triglyceride concentrations.
1 The addition of ezetimibe to a statin is also an effective option. For example, the combination of rosuvastatin plus ezetimibe significantly increases the likelihood of achieving LDL-C goals.
8 However, because such combinations are associated with increased costs and might decrease compliance, the use of a fixed-dose statin combination (eg, simvastatin-eze-timibe) is a reasonable option.
8