Primecuts – This Week In The Journals

November 29, 2010

By Han Na Kim, MD

Faculty Peer Reviewed

Had to drag yourself to work today after a nice Thanksgiving break? Next holiday isn’t coming soon enough for you? Primecuts is here to bring you exciting medical headlines to get you through until Christmas!

Antiretroviral chemoprophylaxis before exposure may decrease but not eliminate HIV transmission risk in HIV-seronegative men and transgender women who have sex with men, the New England Journal of Medicine finds [1]. This multinational study randomized 2499 high-risk subjects to receive a combination antiretroviral pill (emtricitabine and tenofovir disoproxil fumarate [FTC-TDF]) or placebo once daily. They were followed for 3324 person-years (median 1.2 years; maximum 2.8 years). All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually-transmitted infections throughout the study period. Serum drug levels were checked in prespecified subgroups to determine whether drug levels correlated with protective effect. One hundred HIV seroconversions were detected during follow-up: 36 cases from the FTC-TDF group and 64 cases from the placebo group, indicating a 44% reduction in the incidence of HIV with daily antiretroviral chemoprophylaxis. Of the 36 subjects in the FTC-TDF group, serum drug level was detected in 3 of 34 subjects (9%) with HIV infection and in 22 of 43 seronegative control subjects (51%). Greater relative risk reduction (92%) was seen among subjects who were more compliant (based on serum drug levels) with FTC-TDF. This marks a big step in HIV prevention. The New York Times quoted experts who called the study findings a “breakthrough that will accelerate the prevention revolution.” Some expressed fear that this may “speed the evolution of drug-resistant strains” and commented that “the results are encouraging, but it’s not time for gay men to throw away their condoms” [2]. Further investigation is needed regarding pre-exposure chemoprophylaxis in heterosexual men and women, its effect on the emergence of resistance, and other antiretroviral chemoprophylactic regimens before generalized recommendations can be made. More trials of chemoprophylaxis are underway and results are expected to be released over the next two years.    

A JAMA study [3] investigating the effects of different exercise regimens on hemoglobin A1c (HbA1c) in type 2 diabetes also made news in the New York Times [4]. Three exercise regimens were studied: aerobic training alone, resistance training alone, or both. The study enrolled 262 sedentary (not exercising more than 20 minutes on 3 or more days per week) 30- to 75-year old adults in Louisiana with type 2 diabetes and HbA1c levels of 6.5%-11.0%. Subjects were randomized to a no-exercise control group or one of the three exercise groups. The interventions had equal time requirements of 150 minutes per week and lasted for 9 months. The participants were 63% female and 47% nonwhite, with an average body-mass index of 35 kg/m2, HbA1c of 7.7%, and age of 55.8 years. Among the participants, 97% were on diabetes medications, with 18% taking insulin. Only the combination exercise regimen showed improvement in HbA1c. The absolute mean change of HbA1c in the combination group compared to the control group was -0.34% (95% confidence interval [CI], -0.64% to -0.03%; p=0.03). Other exercise groups did not have statistically significant changes in HbA1c level. Although the combination exercise regimen is already recommended for diabetics, this study is the first large randomized trial that directly tested different exercise prescriptions.

Last week the Lancet published a post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study that retrospectively analyzed the safety and efficacy of secondary prevention with long-term statin treatment in patients with coronary artery disease and abnormal liver function tests (LFTs) likely attributable to non-alcoholic fatty liver disease (NAFLD) [5]. The GREACE study was an open-label, unsponsored survival study that randomized 1600 patients with coronary artery disease to atorvastatin or usual care (which could include therapy with statins, including atorvastatin). Patients were followed for an average of three years. The patients had an average age of 58 years, with baseline LDL levels >100 mg/dL and triglycerides <400 mg/dL. Of the study patients, 437 had moderately abnormal baseline LFTs (defined as AST or ALT elevated to less than three times the upper limit of normal). Recurrent cardiovascular events (all-cause mortality, non-fatal myocardial infarction, revascularization, unstable angina, or heart failure) occurred in 10% of the 227 statin-treated/abnormal LFT patients compared with 30% of the 210 no-statin/abnormal LFT patients (68% relative risk reduction [RRR], p <0.0001).

This 68% event reduction in the statin-treated/abnormal-LFT group was greater than the reduction for patients with normal LFTs taking statins: 14% of 653 statin-treated/normal LFT patients had recurrent events versus 23% of 510 no statin/normal LFT patients (39% RRR, p<.0001).

Interestingly, patients with abnormal LFTs who received statin therapy showed improvement in liver enzymes, whereas those who did not receive statin therapy had further worsening of LFTs. The benefits seen with statin therapy were thought to be attributable to the presence of NAFLD in patients with abnormal LFTs, as NAFLD and non-alcoholic steatohepatitis are thought to be independent risk factors for cardiovascular disease. Thumbs up for statin therapy, even for patients with abnormal liver functions tests, if you suspect underlying NAFLD!

While we’re on the subject of cardiovascular disease, ever wonder what’s worse for the heart, binge drinking or regular alcohol consumption? BMJ featured a prospective cohort study suggesting that binge drinking is associated with a higher risk of ischemic heart disease than regular and moderate alcohol consumption [6]. The study was aimed at investigating the effects of alcohol consumption patterns on ischemic heart disease in two countries with contrasting lifestyles: Northern Ireland and France. A total of 9778 middle aged men (aged 50-59) free of ischemic heart disease at baseline were recruited between 1991-1994 from Belfast, Northern Ireland (2405 men) and three cities (Lille, Strasbourg, and Toulouse) in France (7373 men). Participants completed ongoing questionnaires relating to their alcohol consumption and were followed for 10 years. All myocardial infarctions and coronary deaths (“hard” coronary events) were registered. After adjustment for classic cardiovascular risk factors, the hazard ratio for hard coronary events in binge drinkers (>50 grams of alcohol or >5 drinks on at least one day a week) compared with regular drinkers (at least one day a week, alcohol <50 grams if on only one occasion) was 1.97 (95% CI 1.21 to 3.22). The amount of alcohol consumed per week was essentially equivalent in both groups. So remember during this holiday season, moderation is key, space out your drinks! Cheers!

Dr.  Kim is a second year resident at NYU Langone Medical Center

Michael Tanner, MD is a Section Editor, Class Act, Clinical Correlations

Image courtesy of Wikimedia Commons

References

[1] Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. NEJM 10.1056/NEJMoa1011205  http://www.nejm.org/doi/full/10.1056/NEJMoa1011205

[2] http://www.nytimes.com/2010/11/24/health/research/24aids.html?_r=1&ref=health

[3] Church TS, Blair SN, Cocreham S, et al. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes. JAMA. 2010;304(20):2253-2262. (http://jama.ama-assn.org/cgi/content/short/304/20/2253)

[4] http://www.nytimes.com/2010/11/30/health/research/30exercise.html?src=un&feedurl=http%3A%2F%2Fjson8.nytimes.com%2Fpages%2Fhealth%2Fresearch%2Findex.jsonp

[5] Athyros VG, Tziomalos K, Gossios TD, et al. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet DOI:10.1016/S0140-6736(10)  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61272-X/fulltext

[6] Ruidavets J, Ducimetriere P, Evans A, et al. Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). BMJ 2010:341:c6077 doi:10.1136/bmj.c6077 http://www.bmj.com/content/341/bmj.c6077

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