Primary Care's 2014 Lessons: The Research Changing Practice

Linda Brookes, MSc


December 18, 2014

In This Article

2014's Take-Away Messages for Primary Care

A number of notable 2014 publications have already begun and will continue to change clinical practice or have significant implications for the future. It is impossible to list them all, but below is a selection—our top 10—based on recommendations from Medscape's experts across specialties. Reflecting the importance of these topics, there is often a plethora of opinion and data. So in cases where several important publications appeared on the same subject, they are grouped together.

LDL Cholesterol: Lower Is Better

Lowering low-density lipoprotein cholesterol (LDL-C) has become a mainstay of cardiovascular (CV) prevention, based mainly on evidence from statin trials. The results of the IMProved reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), presented at the annual meeting of the American Heart Association (AHA) in November, demonstrated for the first time the incremental benefit achieved with addition of a nonstatin agent (ezetimibe) to statin therapy.[1] The trial also reconfirmed the LDL-C hypothesis, ie, "lower is better", suggesting that lowering LDL-C below previously recommended levels (< 70 mg/dL in most patients) further reduces CV events.

IMPROVE-IT randomly assigned 18,144 patients aged ≥ 50 years who were hospitalized for an acute coronary syndrome (ACS) event to simvastatin 40 mg or fixed-dose combination ezetimibe 10 mg/simvastatin 40 mg. Median LDL-C levels achieved over 9 years were 69.5 mg/dL with simvastatin and 53.7 mg/dL with simvastatin/ezetimibe. After 7 years of follow-up, the primary composite endpoint of CV death, nonfatal myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina, or coronary revascularization was reduced from 34.7% in the simvastatin group to 32.7% in the simvastatin/ezetimibe group (P = .016). This translated into a number needed to treat (NNT) to prevent one of these events of 50.

The investigators suggested that, at least for ACS patients, a target LDL-C close to 50 mg/dL might now be considered appropriate.[2] Although, as commentators pointed out, ezetimibe may not be the only or best way to achieve this.[3] This suggestion also led to some confusion, as the current American College of Cardiology (ACC)/AHA guidelines for reduction of CV risk have abandoned recommendations to treat cholesterol to specific target levels and instead advise prescribing the appropriate intensity of statin therapy for patients deemed to be at sufficient risk.[4]

Vitamin D and Mortality

In 2014, more data became available from meta-analyses investigating a possible association between low circulating levels of 25-hydroxyvitamin D, 25(OH)D, and increased mortality risk, and the effect of supplementation with vitamin D3 in reducing risk. An analysis of data from 95 studies[5] showed that vitamin D insufficiency (25(OH)D < 30 ng/mL) was associated with increased mortality risks of 35% for CV disease; 14% for cancer; 30% for nonvascular, noncancer death; and 35% for all-cause mortality. Supplementation with vitamin D3 significantly reduced overall mortality by 11%. Another analysis of data from 32 studies reported an overall doubling of relative risk between the lowest (0-9 ng/mL) and the highest (> 30 ng/mL) levels of 25(OH)D.[6] A third study analyzed individual data from 26,018 men and women aged 50-79 years from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) and the third US National Health and Nutrition Examination Survey (NHANES III).[7] This analysis found that the lowest 25(OH)D quintile was associated with increased all-cause and CV mortality, and with cancer mortality (though only in subjects with a history of cancer). A Cochrane review produced evidence that vitamin D3 supplementation in healthy adults may reduce mortality, with an NNT of 150 participants over 5 years to save one life.[8]

Despite the evidence to date, the US Preventive Services Task Force (USPSTF) released its latest recommendations stating that current evidence is insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults.[9,10] Almost all of the investigators agreed that data from ongoing clinical trials such as VITAL, CAPS, and VIDAL are needed before screening and supplementation can be recommended on a widespread basis.


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