Guidelines for the management of hyperlipidemia: How can clinicians effectively implement them?

Guidelines support lowering cholesterol to decrease atherosclerotic cardiovascular disease (ASCVD) risk across the entire lifespan with intensive lifestyle intervention, as well as statin and non-statin pharmacotherapy for those at highest risk. Modest improvements in the initiation, use, and adherence to statin therapy in patients with ASCVD have occurred over the past decades. However, studies continue to document a less than desired implementation of guidelines highlighting a substantial and persistent treatment gap. The success of implementation depends on the consideration of a variety of barriers that exist throughout the healthcare delivery system. Further research is needed to comprehensively evaluate these barriers in order to develop appropriate and sustainable interventions to improve guideline implementation.

Atherosclerosis surrogate imaging trials come of age: for better or for worse?

Surrogate atherosclerosis imaging trials have been used to evaluate drugs for regulatory approval. These imaging trials have focused on two methodologies: carotid B-mode ultrasound to measure carotid intima-media thickness (CIMT) and coronary intravascular ultrasound (IVUS) to assess atheroma volume. Recent controversies exist regarding the clinical use of these imaging trials. However, a review of the published CIMT and IVUS trials demonstrates consistent results if the trial is conducted in a coordinated fashion. Proper patient selection appears to be an important criterion to ascertain valid results, especially for CIMT trials. In light of the cost and time involved to complete morbidity trials demonstrating the benefit of potential antiatherosclerotic agents, surrogate imaging trials are necessary to expedite the regulatory approval process.

A review of lipid management in primary and secondary prevention.

Lipid management in primary and secondary prevention reduces cardiovascular morbidity and mortality. Lowering of low-density lipoprotein cholesterol (LDL-C) levels with statins remains the primary goal of therapy. For secondary prevention patients, those with coronary heart disease (CHD) or CHD risk equivalents, intensive LDL-C lowering is recommended, although the precise target value is still debated. For primary prevention, reduction in LDL-C levels is based on patient risk for CHD. In clinical outcome trials to date, statins benefit those who are at moderate to high risk and appear to have less clinical benefit for those at low risk. Yet despite aggressive LDL-C management with statins, there remains a residual risk for CHD events in high-risk patients. Secondary targets have been proposed to decrease this risk, including non-high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and apolipoprotein B, as well as other emerging targets, including LDL particle number and lipoprotein(a). In many high-risk patients, statin monotherapy is unlikely to achieve goals, and combination therapy with other agents is a safe, effective, and optimal therapeutic approach.

Statin and ezetimibe combination therapy in cardiovascular disease.

PURPOSE OF REVIEW: To summarize the available data regarding the benefits of combination therapy with statins and ezetimibe in patients with cardiovascular disease. RECENT FINDINGS: Extensive evidence, mostly in statin outcome trials, has shown that the magnitude of cardiovascular benefit is directly proportional to the degree of LDL cholesterol (LDL-C) reduction. As such, aggressive target goals for LDL-C levels have been established by guideline committees. Although statins are considered first-line agents in lipid therapy, LDL-C targets are difficult to achieve with statin therapy alone. Ezetimibe, a cholesterol absorption inhibitor, has been shown to be well tolerated and effective in lowering LDL-C. Adding ezetimibe to ongoing statin therapy leads to a substantial additional reduction in LDL-C, facilitating the achievement of target goals. SUMMARY: The combination of ezetimibe, a cholesterol absorption inhibitor, and statins has been shown to be well tolerated and effective in lowering LDL-C and high-sensitivity C-reactive protein to target goals. Whether this greater LDL-C reduction translates into reduced cardiovascular events is the subject of ongoing clinical trials. Until such data is available, ezetimibe seems to be a reasonable choice for a second-line, lipid-lowering agent in patients on a potent statin who are not at their LDL-C goal.