Meta-analysis of results from eight randomized, placebo-controlled trials of the effect of cilostazol on patients with intermittent claudication

line CBMmax average of 1.16 mm (normal ⬍0.8 mm), and more than one half the patients had one or more plaques. Compared to atenolol, the lacidipine treatment difference in 4-year CBMmax progression was ⫺0.0227 mm (p⬍0.0001). The yearly mean IMT progression was 0.0145 mm/yr in atenolol-treated and 0.0087 mm/yr in lacidipine-treated patients (p.0002). Lacidipine was associated with more plaque regression and less plaque progression. Clinic BP reduction was similar, but 24 hour ABP changes were greater with atenolol (⫺10/⫺9 mm Hg) than with lacidipine (⫺7/⫺5 mm Hg). There were no between-treatment differences in clinical end points, although the trend for total CVEs favored lacidipine. Conclusions: The greater efficacy of lacidipine on carotid IMT progression and number of plaques per patient, despite a smaller 24-hour ABP reduction, indicates an antiatherosclerotic action of lacidipine independent of its antihypertensive action. Perspective: These are impressive findings. The dihydropyridines have lost favor to the ACE inhibitors in hypertension, primarily because of the favorable effects of the latter on event reduction and reduction in progression of renal disease. The surrogate end point of carotid IMT provides the rationale for a clinical outcome trial comparing lacidipine and an ACE inhibitor. MR

trials. MWD increased 21.4% over baseline in the placebo group and cilostazol 50 and 100 mg BID by 44% and 50%, respectively (p⬍0.05 vs. placebo for both). Change in painfree walking distance increased by 40% on placebo and about 65% with cilostazol. The magnitude of improvement did not vary by age ⬎65 years, gender and diabetes. Cilostazol 100 mg BID increased the HDL-C by 13% and decreased triglycerides by 16%, p⫽0.0001, compared to placebo and pentoxifylline. The physical quality-of-life indicators were significantly improved with active drug. About 14% of patients had an adverse experience on active drug vs. 9% on placebo. The following were more common with cilostazol rather than placebo: headache, palpitations, edema, rhinitis and diarrhea. Conclusions: Cilostazol significantly increases walking distance and quality-of-life measures in patients with claudication without major adverse effects. Perspective: The trial results with cilostazol are impressive and may underestimate the value since it increases over time. The meta-analysis did not consider active smoking, which may have influenced the results. How cilostazol fairs compared to a rigorous exercise program and whether it should be routinely combined with exercise is less clear. MR

Nut and Peanut Butter Consumption and Risk of Type 2 Diabetes in Women

Meta-Analysis of Results From Eight Randomized, Placebo-Controlled Trials of the Effect of Cilostazol on Patients With Intermittent Claudication

Jiang R, Manson JE, Stampfer MJ, et al. JAMA 2002;288:2554 – 60.

Thompson PD, Zimet R, Forbes WP, Zhang P. Am J Cardiol 2002;90:1314 –9.

Study Question: Nuts are high in fiber and unsaturated fatty acids (PUFAs and MUFAs), which may benefit carbohydrate metabolism by improving insulin sensitivity. This study sought to determine whether nut and peanut butter consumption reduce the risk of diabetes. Methods: Women enrolled in the Nurses’ Health Study since 1976 underwent a diet assessment every 4 years from 1980 to 1994. Nut consumption was estimated from the frequency of a serving size of 1 oz from never with nine gradations to more than 6 times a day. Peanuts (botanically classified as legumes) were considered together with other nuts, and peanut butter was estimated as frequency of tablespoons. 83,818 women were available for analysis after exclusions for diabetes, CVD, cancer and extremes of caloric consumption. Information was available on family history of diabetes, body weight, physical activity and other risk factors. The primary outcome was the reporting of type 2 diabetes at follow-up, which was then validated by classic criteria. Results: At baseline, 35% of women reported almost never consuming nuts, 36% less than once/week, 24% 1– 4 times/ week and 5% at least 5 times/week. Women consuming nuts generally weighed less, were less likely to smoke and more likely to exercise. Nut consumption was inversely associated with glycemic load and intake of trans fats. 3206

Study Question: What is the clinical value of cilostazol, a type III phosphodiesterase inhibitor, arterial vasodilator and platelet antagonist, on patients limited by leg claudication? Methods: A meta-analysis of eight randomized, double-blind placebo-controlled trials in 2702 patients. Trial durations ranged from 12 to 24 weeks and were performed in 98 sites in the US (seven trials) and one trial in the UK. Eligible pre-treatment requirements were limiting claudication defined as leg pain or fatigue, an ABI ⱕ0.9 in seven trials and ⱕ0.8 in one trial or a 20 mm Hg decrease in leg pressure post-exercise and less than 20% variability in maximal walk distance (MWD) on two or three consecutive treadmill tests. Patients were excluded with Buerger’s disease, ischemic rest pain, ulcers or gangrene, DVT, arterial revascularization within 3 months, coronary syndromes within 6 months, anticoagulants, ⬎1200 mg of ibuprofen/day or ⬎81 mg ASA/day. Patients received cilostazol in doses of 50,100 or 150 mg BID, pentoxifylline 400 mg TID in three studies or placebo. The trial with the 150 mg BID dose was excluded from efficacy analysis. Results: The mean age was 65 years, 88% were white, 25% were diabetic and duration of claudication was at least 5 years in 40%. Cilostazol improved MWD in six of the eight

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