Journal Club Alcohol and Health: Current Evidence January–February 2007

Featured Article Effect of moderate red wine intake on cardiac prognosis after recent acute myocardial infarction of subjects with Type 2 diabetes mellitus. Marfella R, et al. Diabet Med. 2006;23(9):974–981.

Study Objective To examine whether… moderate alcohol consumption reduces the risk of recurrent myocardial infarction (MI) in people with diabetes

Study Design Randomized trial 131 subjects with diabetes and a recent, initial MI were advised to consume a Mediterranean-type diet and either… –drink 4 ounces of red wine daily or abstain Cardiac function and markers of inflammation and oxidative stress were measured at baseline and 12 months later (n=115) –Measurements did not differ between the groups at baseline

Assessing Validity of an Article about Therapy Are the results valid? What are the results? How can I apply the results to patient care?

Are the Results Valid? Were patients randomized? Was randomization concealed? Were patients analyzed in the groups to which they were randomized? Were patients in the treatment and control groups similar with respect to known prognostic variables?

Are the Results Valid? (cont.) Were patients aware of group allocation? Were clinicians aware of group allocation? Were outcome assessors aware of group allocation? Was follow-up complete?

Were patients randomized? Yes. –The patients were randomized to either abstain or drink 4 ounces of red wine daily.

Was randomization concealed? No. –Randomization was not concealed.

Were patients analyzed in the groups to which they were randomized? Patients appear to have been analyzed in the groups to which they were randomized. However, the following patients were not included in the analyses: 3 who withdrew consent, 2 who had “lack of compliance,” 3 with ultrasound images that were not analyzable, and 8 others lost to follow-up. The degree of adherence to the drinking recommendation was not reported for either group.

Were the patients in the treatment and control groups similar? Yes, the patients in each group who completed the study were similar. –However, the authors did not present the baseline characteristics of all randomized subjects. –At baseline, there were no significant differences between the intervention and control groups. But, the intervention group appeared to have a substantially higher right ventricular relaxation time (42 vs. 10 ms).

Were patients aware of group allocation? Yes. –Subjects were advised to drink wine daily or to abstain.

Were clinicians aware of group allocation? Yes. –Clinicians were aware of group allocation.

Were outcome assessors aware of group allocation? The article does not state whether outcome assessors were aware of group allocation. –However, investigators were aware. –Also, because patients were aware, they could have told echocardiographers.

Was follow-up complete? 131 subjects had enrolled. 115 (88%) completed the study. –57 in the intervention and 58 in the control group

What Are the Results? How large was the treatment effect? How precise was the estimate of the treatment effect?

How large was the treatment effect? At follow-up, markers of both inflammation (i.e., C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-18) and oxidative stress (i.e., nitrotyrosine) were lower in the intervention than in the control group. Cardiac function was also better in the intervention group (i.e., lower myocardial performance index and higher transmitral Doppler flow, pulmonary venous flow, and ejection fraction).

How large was the treatment effect? (cont.) The magnitude of changes in inflammatory markers that is of clinical importance is not known. Changes in concentrations of nitrotyrosine, C- reactive protein, tumor necrosis factor-α, and interleukin-6 were positively related to changes in the markers of cardiac function. Weight loss and diet did not differ between the treatment groups.

How precise was the estimate of the treatment effect? The aforementioned differences were statistically significant.

How Can I Apply the Results to Patient Care? Were the study patients similar to the patients in my practice? Were all clinically important outcomes considered? Are the likely treatment benefits worth the potential harm and costs?

Were the study patients similar to those in my practice? These were patients in Italy with diabetes and MI. Nondrinkers were excluded as were people with unspecified medical or other conditions that would limit their ability to participate. Because of eligibility criteria, the population selected may differ from those in some practices.

Were all clinically important outcomes considered? This study examined surrogate outcomes— outcomes that are not of direct clinical importance like recurrent MI, cardiovascular symptoms, health-related quality of life, transition to heavy drinking or drinking consequences, etc.

Are the likely treatment benefits worth the potential harm and costs? It is premature to answer this question. The harms of recommending moderate alcohol consumption are not well known. Further, the actual clinical benefits remain unknown.

Summary This study found that, over 1 year, many measures of inflammation and ventricular function in subjects with diabetes and a recent MI were… –better in those advised to drink red wine daily than in those advised to abstain. While this was an unblinded trial without detailed compliance data, indirect evidence (e.g., food diaries) suggests that most subjects followed the advice given. Further, weight loss and diet were not different between the groups, suggesting that the changes seen were likely related to wine consumption.

Summary (cont.) However, the findings are too preliminary to lead to any new clinical recommendations: –The harms of recommending drinking are not known. –The clinical importance of the changes in observed outcomes are not clear. –The study group was relatively small and select. –Some of the methodological limitations noted may have affected the observed results. These issues will need to be resolved by larger trials, possibly placebo-controlled trials, with clinical outcomes before patients with diabetes can be advised to drink after having an MI.