Hydroxymethylglutaryl-CoA Reductase Inhibitors

2018 Cholesterol Clinical Practice Guidelines: Synopsis of the 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline

Author/s: 
Grundy, Scott M, Stone, Neil J., Guideline Writing Committee for the 2018 Cholesterol Guidelines

Description:

In November 2018, the American Heart Association and American College of Cardiology (AHA/ACC) released a new clinical practice guideline on cholesterol management. It was accompanied by a risk assessment report on primary prevention of atherosclerotic cardiovascular disease (ASCVD).

Methods:

A panel of experts free of recent and relevant industry-related conflicts was chosen to carry out systematic reviews and meta-analyses of randomized controlled trials (RCTs) that examined cardiovascular outcomes. High-quality observational studies were used for estimation of ASCVD risk. An independent panel systematically reviewed RCT evidence about the benefits and risks of adding nonstatin medications to statin therapy compared with receiving statin therapy alone in persons who have or are at high risk for ASCVD.

Recommendation:

The guideline endorses a heart-healthy lifestyle beginning in childhood to reduce lifetime risk for ASCVD. It contains several new features compared with the 2013 guideline. For secondary prevention, patients at very high risk may be candidates for adding nonstatin medications (ezetimibe or proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) to statin therapy. In primary prevention, a clinician–patient risk discussion is still strongly recommended before a decision is made about statin treatment. The AHA/ACC risk calculator first triages patients into 4 risk categories. Those at intermediate risk deserve a focused clinician–patient discussion before initiation of statin therapy. Among intermediate-risk patients, identification of risk-enhancing factors and coronary artery calcium testing can assist in the decision to use a statin. Compared with the 2013 guideline, the new guideline gives more attention to percentage reduction in low-density lipoprotein cholesterol as a treatment goal and to long-term monitoring of therapeutic efficacy. To simplify monitoring, nonfasting lipid measurements are allowed.

Prescribing Statins to Reduce Cardiovascular Disease – Ten Common Misconceptions

Author/s: 
Schade, David S., Shey, Lynda, Eaton, R. Phillip

Statins (HMG-CoA reductase inhibitors) are one of the most widely prescribed medications in the world. However, their use in patients is often inappropriate because these medications have some unique properties not shared with other pharmaceuticals. This Commentary lists ten common misconceptions concerning statins and provides documentation supporting statin's unique characteristics.

Diagnosis and Management of Nonalcoholic Liver Disease

Author/s: 
Paul, Sonali, Davis, Andrew M.

MAJOR RECOMMENDATIONS

• Patients with incidental hepatic steatosis detected on imaging who lack any liver-related symptoms or signs and have normal liver biochemistries should be assessed for metabolic risk factors (eg, obesity, diabetes mellitus, dyslipidemia) and other causes of hepatic steatosis, including alcohol consumption (>14 drinks per week for women; >21 drinks per week for men) and medications.

• Routine screening for NAFLD in high-risk groups is not advised because of uncertainties surrounding diagnostic tests and treatment options, along with lack of knowledge about long-term benefits and cost-effectiveness of screening.

• The FIB-4 (age, aspartate aminotransferase, alanine aminotransferase, platelets) and NAFLD Fibrosis Score (NFS, which adds body mass index and albumin) are clinically useful tools to predict bridging fibrosis.

• Vibration-controlled transient elastography (VCTE) or magnetic resonance elastography (MRE) can noninvasively assess for advanced fibrosis.

• Weight loss generally reduces hepatic steatosis, either by hypocaloric diet alone or in conjunction with increased physical activity.

• Pharmacologic treatments should be limited to patients with biopsy-proven nonalcoholic steatohepatitis (NASH) and advanced fibrosis.

• Statins can be used to treat dyslipidemia in patients with NAFLD, NASH, and compensated NASH cirrhosis.

Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

Author/s: 
Cholesterol Treatment Trialists' Collaboration

BACKGROUND:

Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safetyamong older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.

METHODS:

In this meta-analysis, randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years. We analysed individual participant data from 22 trials (n=134 537) and detailed summary data from one trial (n=12 705) of statin therapy versus control, plus individual participant data from five trials of more intensive versus less intensive statin therapy (n=39 612). We subdivided participants into six age groups (55 years or younger, 56-60 years, 61-65 years, 66-70 years, 71-75 years, and older than 75 years). We estimated effects on major vascular events (ie, major coronary events, strokes, and coronary revascularisations), cause-specific mortality, and cancer incidence as the rate ratio (RR) per 1·0 mmol/L reduction in LDL cholesterol. We compared proportional risk reductions in different age subgroups by use of standard χ2 tests for heterogeneity when there were two groups, or trend when there were more than two groups.

FINDINGS:

14 483 (8%) of 186 854 participants in the 28 trials were older than 75 years at randomisation, and the median follow-up duration was 4·9 years. Overall, statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77-0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol. We observed a significant reduction in major vascular events in all age groups. Although proportional reductions in major vascular events diminished slightly with age, this trend was not statistically significant (ptrend=0·06). Overall, statin or more intensive therapy yielded a 24% (RR 0·76, 95% CI 0·73-0·79) proportional reduction in major coronary events per 1·0 mmol/L reduction in LDL cholesterol, and with increasing age, we observed a trend towards smaller proportional risk reductions in major coronary events (ptrend=0·009). We observed a 25% (RR 0·75, 95% CI 0·73-0·78) proportional reduction in the risk of coronary revascularisation procedures with statin therapy or a more intensive statin regimen per 1·0 mmol/L lower LDL cholesterol, which did not differ significantly across age groups (ptrend=0·6). Similarly, the proportional reductions in stroke of any type (RR 0·84, 95% CI 0·80-0·89) did not differ significantly across age groups (ptrend=0·7). After exclusion of four trials which enrolled only patients with heart failure or undergoing renal dialysis (among whom statin therapy has not been shown to be effective), the trend to smaller proportional risk reductions with increasing age persisted for major coronary events (ptrend=0·01), and remained non-significant for major vascular events (ptrend=0·3). The proportional reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease (ptrend=0·2), but appeared smaller among older than among younger individuals not known to have vascular disease (ptrend=0·05). We found a 12% (RR 0·88, 95% CI 0·85-0·91) proportional reduction in vascular mortality per 1·0 mmol/L reduction in LDL cholesterol, with a trend towards smaller proportional reductions with older age (ptrend=0·004), but this trend did not persist after exclusion of the heart failure or dialysis trials (ptrend=0·2). Statin therapy had no effect at any age on non-vascular mortality, cancer death, or cancer incidence.

INTERPRETATION:

Statin therapy produces significant reductions in major vascular events irrespective of age, but there is less direct evidence of benefit among patients older than 75 years who do not already have evidence of occlusive vascular disease. This limitation is now being addressed by further trials.

FUNDING:

Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation.

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