Use of Ranolazine for the Treatment of Coronary Microvascular Dysfunction.

Coronary microvascular dysfunction (CMD) is defined as a mismatch of myocardial blood supply and oxygen consumption due to a dysfunction of the coronary microvessels. Up to 20-30% of patients with CMD have progressive worsening of symptoms with significant impairment of quality of life. Large-scale randomized studies of the pharmacologic treatment of CMD are lacking. Classic anti-ischemic drugs are the initial form of treatment, but efficacy is often limited. Ranolazine has a unique mechanism of action that does not affect blood pressure or heart rate. When added to existing anti-anginal agents, ranolazine improved at least one domain in eight of ten studies in which a questionnaire was used to assess patient health status. Five studies evaluated coronary arterial flow reserve (CFR), reporting that patients with low values had significant improvement in CFR and suggesting that those with more severe CMD respond more favorably to ranolazine. In two studies, exercise duration and time to myocardial ischemia were significantly increased after treatment with ranolazine. Data are lacking for ranolazine use as the sole agent for CMD treatment. Some questions remain to be answered regarding ranolazine use for CMD. Larger studies of longer duration are needed to verify the effectiveness of ranolazine in the treatment of CMD.

Impact of carvedilol on the serum lipid profile.

OBJECTIVE: To examine the evidence regarding the impact of carvedilol on the serum lipid profile. DATA SOURCES: Searches in MEDLINE and International Pharmaceutical Abstracts (1966-December 2007) were conducted. Search terms included carvedilol, cholesterol, lipids, hyperlipidemia, and beta-blockers. STUDY SELECTION AND DATA EXTRACTION: Published studies and case reports that evaluated the impact of carvedilol on the lipid profile were reviewed. One study was excluded because it evaluated carvedilol for an off-label use and was a small Phase 2 pilot study that evaluated the results of only 10 patients. DATA SYNTHESIS: Twelve studies were available for review; 6 of these compared carvedilol with beta(1)-selective antagonists. Three studies compared carvedilol with other antihypertensive medications; 2 of those studies evaluated total cholesterol only. Carvedilol alone was evaluated for its effects on lipids in 3 small single-group studies. In 4 of the 12 studies, carvedilol independently improved the lipid profile significantly, while the drug had a nonsignificant, neutral effect on the lipid profile in 3 studies. Furthermore, in 4 of the 12 studies, carvedilol was compared with other antihypertensive medications. In 3 of these 4 studies, the other drugs worsened the lipid profile significantly compared with carvedilol, while carvedilol significantly improved the lipid profile in the other study. Finally, carvedilol had a potentially negative effect on high-density lipoprotein cholesterol in a single-group study, but p values were not reported. CONCLUSIONS: It is clear that beta(1)-selective antagonists worsen the lipid profile compared with carvedilol. However, it is unclear whether carvedilol independently makes an improvement or has a neutral effect on the lipid profile. Carvedilol should be an important treatment consideration in patients with heart failure and/or hypertension with dyslipidemia. However, many questions remain regarding this issue.

Comparing the Impact of Prescription Omega-3 Fatty Acid Products on Low-Density Lipoprotein Cholesterol.

Elevated levels of triglycerides are associated with pancreatitis and an increased risk of coronary heart disease. Numerous pharmacologic therapies are available to treat hypertriglyceridemia, including prescription omega-3 fatty acids, which reduce triglyceride levels by 20-50%. Available data indicate the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be beneficial for secondary prevention of coronary heart disease. Products containing DHA may increase low-density lipoprotein cholesterol (LDL-C) and, subsequently, coronary heart disease risk. We reviewed prescription omega-3 fatty acid products, of which two-omega-3 acid ethyl esters (OM3EE) and omega-3 carboxylic acid (OM3CA)-contain both DHA and EPA, whereas the other-icosapent ethyl (IPE)-contains EPA only. We identified three retrospective chart reviews and three case reports comparing IPE with OM3EE, whereas two studies compared IPE with placebo. We also reviewed the major studies of OM3EE versus placebo used to gain US FDA approval. LDL-C levels decreased or did not increase significantly in all available studies and case reports in patients receiving the IPE product, with the best data supporting a dose of 4 g per day. The majority of studies only included patients taking IPE concomitantly with statins, but limited data from one study using IPE monotherapy showed a small reduction in LDL-C. Many questions remain regarding IPE, including whether the product reduces cardiovascular events and mortality.

Nesiritide for treatment of heart failure due to right ventricular dysfunction.

Little information exists regarding the use of nesiritide for treatment of right-sided heart failure. Similarly, little information is available regarding routine use of combination nesiritide and diuretics as initial therapy to relieve edema due to heart failure. Nesiritide may be beneficial in combination with diuretics because it reduces activity of the renin-angiotensin-aldosterone system. It is unclear how potent nesiritide is as a diuretic. Patients exhibit wide variability in clinical response from the diuretic effects of the drug. Two patients were given a combination of nesiritide and diuretics as initial treatment of right-sided heart failure; both experienced significant diuresis and weight loss. Further literature is needed to clarify the role of nesiritide in the treatment of right-sided heart failure.

Anticoagulation in patients with dilated cardiomyopathy and sinus rhythm: a critical literature review.

BACKGROUND: The risk of thromboembolism in chronic heart failure and the risk-to-benefit ratio of anticoagulation in this population are poorly defined. METHODS AND RESULTS: A PubMed/MEDLINE search of published trials was performed. Twenty-four studies were identified after exclusion of individual case reports. All studies were prospective or retrospective observational reports, either independent studies or secondary analyses of prospective clinical trials in patients with heart failure. Prevalence estimates ranged of thromboemboli ranged from 3% to 50% and incidence estimates ranged from 1.5 to 3.5/100 patient-years. Although no randomized data of therapeutic anticoagulation were identified, a secondary analysis of one study suggested event reduction in patients receiving warfarin anticoagulation; other studies failed to suggest such benefit. Overall bleeding estimates in warfarin-treated patients ranged from 2.3 to 6.8/100 patient-years. Intracranial hemorrhage rates were 0.62 to 0.9/100 patient-years but increased with age. Only one study suggested that aspirin was beneficial in reducing clinically significant emboli. CONCLUSIONS: Although patients with chronic heart failure and left ventricular dilation have a higher risk of thromboembolism, data are insufficient to recommend warfarin or aspirin prophylaxis in the absence of additional indications for such therapy.