Top POEMs of 2013: Miscellaneous

Fewer Deaths/Strokes/Revascularizations with Metformin Than Glipizide

Clinical question: Does metformin affect cardiovascular events in patients with type 2 diabetes?

Bottom line: Over 5 years, treatment with metformin for 3 years, along with other hypoglycemics as needed, reduced the likelihood of death, nonfatal stroke, or the need for vascularization as compared with treatment beginning with glipizide. Cardiovascular events were not individually reduced with metformin as compared with glipizide. (LOE = 1b-)

Reference: Hong J, Zhang Y, Lai S, et al, for the SPREAD-DIMCAD Investigators. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care 2013;36(5):1304-1311.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Uncertain

Setting: Outpatient (any)

Synopsis: These Chinese authors enrolled patients with type 2 diabetes and coronary artery disease and followed them up for a median of 5 years. The average age of all 304 patients was 63.3 years; 77% were men. After stopping current treatment (which included insulin in approximately 10% of the group), patients were randomized, with allocation concealment unknown, to receive either glipizide 30 mg daily or metformin 1500 mg daily, with additional treatment added as needed, to achieve an average glycated hemoglobin level of 7.0%. Twenty-five percent of patients in each group ended up receiving insulin in addition to the study drug. Using intention-to-treat analysis, the investigators compared the incidence of recurrent cardiovascular events in the 2 groups, including death, nonfatal stroke, or need for revascularization. After a median follow-up of 5 years, one or more events occurred in 35.1% of patients treated with glipizide and 25% of patients treated with metformin (adjusted hazard ratio = 0.54; P = .026), which translates to a number needed to treat of 9.4 for 5 years. Death rates were not different between the 2 groups. This small study reinforces the findings from the long-ago study (Diabetes 1970;19:747-830) that resulted in FDA warnings of an increased risk of cardiovascular events with sulfonylurea hypoglycemics.

Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA

Clinically Significant Bleeding Occurs in 3.8% Per Year of Pts Aged 65+ Years Using Warfarin

Clinical question: What are the real-world rates of hemorrage after the initiation of warfarin?

Bottom line: The risk of hemorrhage is 2.9% per person-year for patients aged 66 years to 75 years, and 4.6% per person-year for those older than 75 years. The risk is also higher for patients with a higher CHADS(2) risk score. It is important to keep this in mind when reading randomized controlled trials that report lower rates, which make the net benefit of anticoagulation appear more favorable than it probably is in the real world. (LOE = 2b)

Reference: Gomes T, Mamdani MM, Holbrook AM, Paterson JM, Hellings C, Juurlink DN. Rates of hemorrhage during warfarin therapy for atrial fibrillation. CMAJ 2013;185(2):E121-E127.

Study design: Cohort (retrospective)

Funding source: Government

Setting: Population-based

Synopsis: In randomized controlled trials, the rate of major bleeding is typically between 1% and 3% per year. These patients are closely monitored and older patients are often excluded from these trials. These Canadian researchers linked pharmacy and hospital databases to identify patients older than 65 years with atrial fibrillation who initiated warfarin therapy over a 1-year period between 2007 and 2008. Then they determined each patient's CHADS(2) score, a measure of risk of venous thromboembolism (VTE) and any major bleeding episodes. The latter were defined as a visit to the emergency department or admission to the hospital for hemorrhage. The authors followed up the patients for up to 5 years, or until they stopped taking warfarin or had a hemorrhagic episode. The average age of patients in the cohort was 77 years, and a one third had a CHADS(2) score of 3 or higher. The risk of hemorrhage was highest in the first month of therapy (1% overall; 11.8% per person-year) and in patients with higher CHADS(2) scores. For example, patients with a CHADS(2) score of 4 or higher had a 6.0% risk per person-year, compared with 1.8% for those with a score of 2 or lower. The overall risk over the entire treatment period was 3.8% per person-year. This is higher than that reported by most studies, but somewhat lower than that seen in some other studies. The latter studies typically included shorter follow-up periods. Patients older than 75 years also had higher rates of hemorrhage than patients aged 66 to 75 years (4.6% vs 2.9%). Of patients admitted for hemorrhage, 1 in 5 died during or shortly after the hospitalization. One limitation is that the authors were unable to fully ascertain the use of aspirin or nonsteroidal antiinflammatory drugs because over-the-counter drug use is not tracked by the pharmacy database.

Mark H. Ebell, MD, MS
Associate Professor
University of Georgia
Athens, GA

Cutaneous Warts in Kids: Half Disappear Within a Year

Clinical question: What happens to warts on kids?

Bottom line: Among children with warts, approximately half will be free of warts 1 year later, even if left untreated. This information can be useful when advising patients and parents whether to pursue treatment. (LOE = 2b)

Reference: Bruggink SC, Eekhof JA, Egberts PF, van Blijswijk SC, Assendelft WJ, Gussekloo J. Natural course of cutaneous warts among primary schoolchildren: a prospective cohort study. Ann Fam Med 2013;11(5):437-441.

Study design: Cohort (prospective)

Funding source: Government

Setting: Population-based

Synopsis: Specially trained medical students evaluated the hands and feet of 1100 schoolchildren in 3 Dutch grade schools for the presence of warts. At the time of the first examination, one third had warts (42% had common warts, 70% had plantar warts). Among those with warts, nearly half had multiple warts and one third had warts larger than 1 cm. Approximately 1 year later the researchers re-examined the kids and approximately half the warts were gone. Although one third of these children received wart treatment, the treated children were actually less likely to have wart resolution!

Henry C. Barry, MD, MS
Michigan State University
East Lansing, MI

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