Diabetes and cardiovascular disease: focus on glucagon-like peptide-1 based therapies.

Type 2 diabetes is a well known risk factor for cardiovascular disease (CVD). While glycemic control has consistently been shown to prevent microvascular complications, large randomized trials have not demonstrated the same consistent beneficial effects of intensive glycemic control in improving cardiovascular (CV) outcomes. Thus, optimal glucose control alone is not sufficient to reduce CV risk. Aggressive management of CV risk factors such as blood pressure, lipids, and body weight is also necessary. A growing body of evidence suggests that the recently available glucagon-like peptide 1 receptor (GLP-1R) agonists have beneficial CV effects beyond glucose control. Studies have demonstrated beneficial effects in the myocardium, endothelium, vasculature and various markers of cardiovascular risk such as body weight, blood pressure and dyslipidemia. Despite the growing evidence, large, randomized, blinded clinical trials with hard CV endpoints have not been performed. Most human studies have been small, and have focused on surrogate endpoints. The findings need to be confirmed by prospective, randomized cardiovascular outcomes trials. In this review we examine the GLP-1R agonist data on weight reduction, blood pressure lowering, beneficial changes in dyslipidemia, and improvements in myocardial and endothelial function. The safety as well as potential role of these agents in treatment regimens for type 2 diabetes is also addressed.

The ezetimibe controversy: implications for clinical practice.

Low-density lipoprotein cholesterol (LDL-C) remains the primary target of lipid-lowering therapy. Achieving LDL-C goals as outlined by the National Cholesterol Education Program Adult Treatment Panel III can be difficult with statins alone; therefore, adjunctive therapy is often indicated to reduce cardiovascular risk. Ezetimibe, a potent inhibitor of intestinal cholesterol absorption, has been shown to be safe, tolerable and effective at lowering LDL-C, non-high-density lipoprotein cholesterol and apolipoprotein B, each of which has been correlated with improved clinical outcomes, alone or in combination with a statin. However, because of randomized trials that demonstrated mixed results about atherosclerotic plaque regression via carotid intima-media thickness and a concern about cancer risk, ezetimibe's role in lipid therapy has been questioned. Currently, a large randomized controlled trial is in progress to answer if ezetimibe improves clinical outcomes in patients with high-risk acute coronary syndrome. A smaller trial in patients with chronic kidney disease demonstrated reduced clinical events, including myocardial infarction, stroke and revascularization for patients taking the combination of ezetimibe and simvastatin versus those taking statin or placebo alone. In this paper, we review the trials that have led to the ezetimibe controversy and then discuss the possible role of ezetimibe in specific patient populations until the results of ongoing clinical trials are known.

Thiazolidinediones in type 2 diabetes: a cardiology perspective.

OBJECTIVE: To examine the cardiovascular effects of thiazolidinediones (TZDs), discuss concerns regarding this drug class and its relation to heart failure (HF) and myocardial infarction (MI), and address the clinical implications of HF and MI. DATA SOURCES: Literature was accessed through MEDLINE (1979-April 2008) using the search terms type 2 diabetes mellitus, thiazolidinediones, cardiovascular events, heart failure, myocardial infarction, and edema. Reviews, meta-analyses, clinical trials, observational studies (case-control, cohort), and descriptive studies (case reports, case series) were included. STUDY SELECTION AND DATA EXTRACTION: All articles that were written in English and identified from the data sources were reviewed. DATA SYNTHESIS: The American Diabetes Association recommends metformin as first-line therapy for type 2 diabetes, with the subsequent addition of a TZD, sulfonylurea, or insulin if the target is not met. Beyond glucose lowering, TZDs improve various factors associated with cardiovascular risk. Whether the effects translate into beneficial cardiovascular outcomes is controversial. In PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events), pioglitazone did not produce a significant reduction in the primary endpoint that included a composite of coronary and vascular deaths, but the secondary composite endpoint of all-cause mortality, MI, or stroke was significantly reduced. Concerns related to HF have led to warnings in the labeling of TZDs. The drugs are contraindicated in patients with New York Heart Association Class III or IV HF. Rosiglitazone, but not pioglitazone, is associated with an increased risk of myocardial ischemic events, although the absolute magnitude is extremely small. CONCLUSIONS: Although the glycemic efficacy of TZDs is comparable to that of metformin, adverse effects and higher costs make TZDs less appealing for initial therapy. Among the TZDs, pioglitazone should be considered based on cardiovascular safety data. In combination with metformin, pioglitazone may be particularly beneficial for patients with diabetes and metabolic syndrome. For patients on rosiglitazone who are achieving glycemic goals and tolerating the therapy without apparent complications, rosiglitazone may be continued.

Medication adherence following coronary artery bypass graft surgery: assessment of beliefs and attitudes.

BACKGROUND: The medication management of patients following coronary artery bypass graft (CABG) surgery may include antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors, and statins. However, poor adherence is common, and patient attitudes and beliefs play a role in adherence. OBJECTIVE: To evaluate the association between self-reported adherence and the beliefs patients have about cardiovascular medicines used after CABG. METHODS: Adults were surveyed 6-24 months following CABG. The validated Beliefs about Medicines Questionnaire (BMQ) assessed attitudes concerning the Specific Necessity, Specific Concerns, General Harm, and General Overuse of medicines. The validated medication adherence scale assessed self-reported adherence. Analysis included univariate comparison (BMQ scales) and multivariate logistic regression (identification of adherence predictor variables). RESULTS: Of 387 patients surveyed, 132 (34%) completed the questionnaire. Nonparticipants were more likely to be female and have undergone 1- or 2-vessel CABG procedures compared with 3- or 4-vessel procedures. Subjects were primarily English-speaking, white, and male. Adherent behavior was reported in 73 of 132 patients (55%). The average period between CABG and the survey was 16 months. Nonadherent patients were in stronger agreement on the General Overuse (p = 0.01) and General Harm (p = 0.04) scales. The adjusted odds of adherent behavior were significantly lower, with an increasing General Overuse score (OR 0.83; 95% CI 0.72 to 0.95; p = 0.007); an annual income of $50,000 to $100,000 relative to less than $20,000 (OR 0.36; 95% CI 0.14 to 0.91; p = 0.031), and a living status of "alone" compared with "with adults and no children" (OR 0.20; 95% CI 0.06 to 0.65; p = 0.007). The odds ratio of self-reported adherence was higher with increasing age (OR 1.05; 95% CI 1.01 to 1.09; p = 0.023). CONCLUSIONS: In summary, patient beliefs and attitudes regarding medications, along with other social, economic, and demographic factors, help explain differences in self-reported adherence to standard drug therapy following CABG.

Amiodarone for atrial fibrillation following cardiac surgery: development of clinical practice guidelines at a university hospital.

Atrial fibrillation (AF) usually develops within the first 72 h following cardiac surgery, and is often self-limiting. Within 48 h of acute onset of symptoms, approximately 50% of patients spontaneously convert to normal sinus rhythm. Thus, the relative risks and benefits of therapy must be carefully considered. The etiology of AF following cardiac surgery is similar to that in non-surgical patients except that pericardial inflammation and increased adrenergic tone play an increasingly important role. Further, AF after surgery may be associated with transient risk factors that resolve as the patient moves out from surgery, and the condition is less likely to recur compared to AF arising in other circumstances. Immediate heart rate control is important in preventing ischemia, tachycardia-induced cardiomyopathy, and left ventricular dilatation. At our institution, amiodarone is frequently used as a first-line drug for treating AF after cardiac surgery. Inconsistent prescribing practices, variable dosage regimens, and a lack of consensus regarding the appropriate use of amiodarone prompted the need for developing practice guidelines. Multidisciplinary collaboration between the departments of cardiac surgery, pharmacy, and anesthesiology led to the development of a protocol for postoperative AF. We review the clinical evidence from published trials and discuss our guidelines, defining amiodarone use for AF in the cardiac surgery setting.

Medication use as a risk factor for falls among hospitalized elderly patients.

PURPOSE: The relationship between medication use and falls among hospitalized elderly patients was studied. METHODS: Sixty-two patients 65 years of age or older who fell during hospitalization were randomly selected from incident reports of falls and matched for age, sex, and discharge date with 62 patients who did not fall. Data on demographic characteristics, vital signs, laboratory test variables, drug therapy, and the presence of other known risk factors for falls were collected retrospectively and compared between the groups. RESULTS: Nonsteroidal antiinflammatory drug (NSAID) use was more frequent in patients who fell than in control patients. NSAID use was a significant predictor of falls and was associated with a 10-fold increase in the likelihood of falling. Opioid analgesics were given more frequently to control patients and were not associated with falls. Dementia, the only non-medication-related independent predicator of falls, was associated with a 21-fold greater risk of falling. CONCLUSION: In hospitalized elderly patients, there was a significant association between NSAID use and falls, an effect largely accounted for by low-dose aspirin.

Statin initiation following coronary artery bypass grafting: outcome of a hospital discharge protocol.

STUDY OBJECTIVES: To evaluate the outcome of a hospital discharge statin drug therapy initiation protocol following coronary artery bypass graft (CABG) surgery. Our goal was to measure the percentage of patients receiving statin drugs at hospital discharge and at a post-hospital discharge assessment following the implementation of the statin drug therapy initiation protocol. We also evaluated low-density lipoprotein cholesterol (LDL-C) goal attainment (ie, < 100 mg/dL), safety monitoring, and tolerability of the statin drug. DESIGN: Single-center, observational study with a historical control group. SETTING: University-affiliated health system with a comprehensive heart care program that included a 14-bed cardiac surgery ICU. Approximately 400 CABG procedures are performed annually. PATIENTS: Patients who underwent CABG surgery were eligible for inclusion in the study. The exclusion criteria were as follows: contraindications to statin therapy; refusal to take a statin drug; refusal to give informed consent; and age < 18 years. INTERVENTION: A protocol was implemented to recommend treatment with a statin drug at hospital discharge in all post-CABG surgery patients if the presurgical LDL-C level was > 100 mg/dL or the patient was receiving a statin prior to hospital admission. The protocol also included a presurgical assessment of lipoprotein levels and hepatic function. All cardiac surgery staff were educated regarding the specifics of the protocol. RESULTS: A total of 403 patients were included in the study. The historical control group (202 subjects) and the intervention group (201 subjects) were similar with respect to gender, age, and baseline lipoprotein levels. The follow-up assessment interval was approximately 6 months in both groups. Overall, patients were more likely to receive a statin at hospital discharge in the intervention group compared to the control group (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3 to 2.0). Attainment of the goal for LDL-C level was similar between the intervention and control groups in the overall sample. Patients who were not at their LDL-C goal at baseline were more likely to have a follow-up LDL-C level of < 100 mg/dL in the intervention group (RR, 1.9; 95% CI, 1.0 to 3.5). The rate of liver function assessment was similar in the control and intervention groups. No patients in either group experienced elevations of alanine aminotransferase levels that were more than three times the upper limit of normal, and no cases of muscle toxicity were noted. CONCLUSION: The initiation of therapy with a statin drug at hospital discharge following CABG surgery was associated with increased utilization rates. The LDL-C goal attainment improved in patients who were not at their goal prior to surgery. However, the persistence of medication use declined within 6 months. Statin therapy initiation was well-tolerated in this cohort of patients.

Diagnosis and treatment of Graves disease.

OBJECTIVE: To review the etiology, diagnosis, and clinical presentation of Graves disease and provide an overview of the standard and adjunctive treatments. Specifically, antithyroid drugs, beta-blockers, inorganic iodide, lithium, and radioactive iodine are discussed, focusing on current controversies. DATA SOURCES: Primary articles were identified through a MEDLINE search (1966-July 2000). Key word searches included beta-blockers, Graves disease, inorganic iodide, lithium, methimazole, and propylthiouracil. Additional articles from these sources and endocrinology textbooks were also identified. We agreed to include articles that would highlight the most relevant points, as well as current areas of controversy. DATA SYNTHESIS: Graves disease is the most common cause of hyperthyroidism. The 3 main treatment options for patients with Graves hyperthyroidism include antithyroid drugs, radioactive iodine, and surgery. Although the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI) have similar efficacy, there are situations when 1 agent is preferred. MMI has a longer half-life than PTU, allowing once-daily dosing that can improve patient adherence to treatment. PTU has historically been the drug of choice for treating pregnant and breast-feeding women because of its limited transfer into the placenta and breast milk. Adjuvant therapies for Graves disease include beta-blockers, inorganic iodide, and lithium. beta-Blockers are used to decrease the symptoms of hyperthyroidism. Inorganic iodide is primarily used to prepare patients for thyroid surgery because of its ability to decrease the vascularity of the thyroid gland. Lithium, which acts in a manner similar to iodine, is not routinely used due to its transient effect and the risk of potentially serious adverse effects. In the US, radioiodine therapy has become the preferred treatment for adults with Graves disease. It is easy to administer, safe, effective, and more affordable than long-term treatment with antithyroid drugs. Hypothyroidism is an inevitable consequence of radioiodine therapy. Radioiodine is contraindicated in pregnant women because it can damage the fetal thyroid gland, resulting in fetal hypothyroidism. Bilateral subtotal thyroidectomy, which was once the only treatment available, is now performed only in special circumstances. In addition to the normal risks associated with surgery, laryngeal nerve damage, hypoparathyroidism, and hypothyroidism can occur following that procedure. CONCLUSIONS: Despite extensive experience with medical management, controversy prevails regarding choosing among the various drugs for treatment of Graves disease. None of the treatment options, including antithyroid drugs, radioiodine, and surgery, is ideal. Each has risks and benefits, and selection should be tailored to the individual patient.