Primecuts – This Week In The Journals

May 31, 2011

By Varun Verma, MD

Faculty Peer Reviewed

Our thoughts and prayers this week are with the victims of Joplin, Missouri, who struggle to rebuild their lives after being struck with one of the deadliest tornadoes in US history. Although we can do little about unpredictable natural occurrences, this week’s medical journals reveal some promising interventions that may help us improve the health of our patients.

The New York Times highlighted the National Institutes of Health clinical trial AIM HIGH, [1] the results of which call into question the role of niacin in clinical practice and the importance of high-density lipoprotein (HDL) cholesterol as a risk factor for cardiovascular disease. The authors randomized 3,414 participants with low HDL and high triglycerides to either simvastatin and a placebo, or simvastatin and extended-release niacin (Niaspan) and followed them for 32 months. [2] The trial ended 18 months early because those in the Niaspan group were no less likely to suffer fatal or non-fatal myocardial infarctions, be hospitalized for acute coronary syndrome, or undergo revascularization procedures. More importantly, those in the Niaspan group were at increased risk of developing ischemic stroke: 28 strokes (1.6%) versus 12 strokes (0.7%) in the control group. [3] The fact that Niaspan did indeed increase HDL and lower triglycerides emphasizes that much remains to be discovered about cholesterol homeostasis. Although there will certainly be other studies to tackle the question of the effects of HDL and triglycerides on cardiovascular disease, given the increased risk of ischemic stroke with Niaspan, I will likely not recommend it to any of my patients with well-controlled low-density lipoprotein (LDL) cholesterol at this time.

Staying with cardiology for the moment, a prospective study in JAMA revealed that new-onset atrial fibrillation (AF) in middle aged women was independently associated with elevated all-cause, cardiovascular, and non-cardiovascular mortality. [4] The study included 34,722 women aged 45 or older (median follow-up of 15 years) with low overall cardiovascular risk factors, who were free of AF at baseline. In multivariate models, hazard ratios of new onset AF for all-cause, cardiovascular, and non-cardiovascular mortality were 2.14 (95% CI, 1.64-2.77), 4.18 (95% CI, 2.69-6.51), and 1.66 (95% CI, 1.19-2.30), respectively.  Interestingly, women with only paroxysmal AF, although not at increased risk for all-cause and non cardiovascular death, still remained at increased risk of cardiovascular death (HR, 2.94; 95% CI, 1.55-5.59; P=.001) after adjustment for cardiovascular risk factors. The authors conclude that not all of the mortality risk associated with AF could be accounted for by the development of cardiovascular disease, which underscores the need for more effective primary AF prevention strategies. When more closely analyzing the baseline characteristics of the incident AF group vs the non-AF group, the only statistically significant difference was prevalence of hypertension at the time of incident AF.

While digesting the next study, one wonders whether cardiac medications will one day run free like fluoride in our drinking water. The 400-participant 12-week randomized controlled trial in PLos ONE (an open-access peer-reviewed journal published by the Public Library of Science that I first discovered in the News section of BMJ) proclaims that a cardiovascular “polypill” halved the predicted risk of heart disease and stroke when compared to placebo in participants with no indications for any of these medications. The pill contains 75 mg aspirin, 10 mg lisinopril, 12.5 mg hydrochlorothiazide, and 20 mg simvastatin. [5] Although the participants were people with elevated cardiovascular risk (5-year Framingham risk of at least 7.5%), they had no indications for any of these medicines. The study was conducted in seven countries: Australia, Brazil, India, Netherlands, New Zealand, the United Kingdom, and the United States. Before we all reach for our prophylactic pill cabinets, the authors quite rightly point out the many limitations to their study, including the relatively short follow-up, the narrow patient population, and (perhaps most striking) the fact that the predicted reductions in cardiovascular risk are based on indirect estimates. Systolic blood pressure decreased by 9.9 mmHg (95% CI, 7.7-12.1) and LDL cholesterol by 0.8 mmol/L (95% CI, 0.6-0.9) compared with placebo. This is not the first study to consider a combination pill to address cardiovascular risk factors; a study from India was published in 2009 in Lancet with a drug consisting of three blood pressure-lowering drugs, a statin, aspirin, and folic acid. Given the prevalence, cost, morbidity, and mortality of cardiovascular disease, I assume it will not be the last.

Our last two studies hail from the Archives of Internal Medicine. To those of us who realize the importance of a multipronged approach to the practice of modern medicine, the findings of the next study should come as no surprise. This one-year randomized controlled trial examined the effect of involving a language-concordant layperson in the colorectal cancer screening process. [6] Patients assisted by a “healthcare navigator” were more likely to undergo fecal occult blood testing than control patients (33.6% vs 20.0%; P < .001) and also to be screened by colonoscopy (26.4% vs 13.0%; P < .001). Impressively, these patients were also more likely to have adenomas detected (8.1% vs 3.9%; P = .06). Whatever the reason for low screening rates among our patients–lack of trust in physicians, absence of symptoms, a fundamental disconnect experienced when communicating through an interpreter–the study outlines a simple and effective intervention. Hiring laypersons from the community to provide a health care intervention, emotional support, and empathy has been tested in the realm of global health. Partners In Health, based in Boston, trains and employs “accompagnateurs routinely in their HIV and TB compliance efforts throughout Haiti and Rwanda. Perhaps we will step away from our lone-ranger role as physicians, and treat medicine like the team sport it is.

A much overlooked problem in primary care practice is insomnia, particularly among the elderly. Since there are downsides to simply prescribing another drug (poly-pharmacy, cost, nonadherence), it is encouraging to see another study outline a simple intervention that delegates responsibility to another team member, in this case a nurse practitioner. The randomized trial in the Archives of Internal Medicine examined 79 older adults with chronic insomnia and found brief behavioral treatment more efficacious than handing out printed materials on insomnia. [7] The intervention arm consisted of a 45- to 60-minute individual session followed by a 30-minute follow-up session 2 weeks later and 20-minute telephone calls after 1 and 3 weeks.  Four main behavioral interventions were emphasized: “Reduce time in bed, get up at the same time every day regardless of sleep duration, do not go to bed unless sleepy, and do not stay in bed unless asleep.” Napping was discouraged. The study also displayed impressive potential for durability: at 6 months, 64% of patients in the treatment arm no longer met DSM-IV criteria for insomnia.

Dr. Verma is a 2nd year resident at NYU Langone Medical Center

Peer reviewed by Michael Tanner, MD, section editor, Clinical Correlations

Image courtesy of Wikimedia Commons


1. Harris, Gardener. Study Questions Treatment Used in Heart Disease New York Times. Published online May 28, 2011.

2. AIM-HIGH Investigators.  The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol.  Rationale and study design.  The Atherosclerosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH). Am Heart J. 2011;161(3):538-543.

3. NHLBI Communications Office. NIH stops clinical trial on combination cholesterol treatment. Lack of efficacy in reducing cardiovascular events prompts decision.

4. Conen D, Chae CU, Glynn RJ, et al. Risk of death and cardiovascular events in initially healthy women with new-onset atrial fibrillation.  JAMA. 2011;305(20):2080-2087.

5. Rodgers A, PILL Collaborative Group, et al. An international randomised placebo-controlled trial of a four-component combination pill (“Polypill”) in people with raised cardiovascular risk. PLoS ONE. 6(5):e19857.

6. Lasser K, Murillo J, Lisboa S, et al. Colorectal cancer screening among ethnically diverse, low-income patients: a randomized controlled trial. Arch Intern Med. 2011;171(10):906-912.

7. Buysse D, Germain A, Moul DE, et al. Efficacy of brief behavioral treatment for chronic insomnia in older adults. Arch Intern Med. 2011;171(10):887-895.