Hemorrhagic events lead to an increase in international normalized ratio in patients on warfarin.

PURPOSE: The purpose of this study was to support a theory that in a cohort of patients on warfarin with bleeding and an elevated international normalized ratio (INR), the INR elevation was related to the bleeding episode and not necessarily over anticoagulation from warfarin. METHODS: The medical records of patients taking warfarin who presented with a bleeding event and high INR were reviewed over an 18-month period. Data collected included warfarin dose, INR, and hematocrit 90 days before and after the bleeding event. Patients were interviewed to ascertain whether any interactions with warfarin occurred which could explain the high INR. RESULTS: Eighteen patients were identified who presented with bleeding, a high INR, and no identifiable reason for the elevated INR. A significant increase in INR was observed from baseline to the event (2.5 ± 0.36 vs 6.2 ± 3.19; P = .0002), but the INR during all periods of follow-up did not differ from baseline (P = .35-.99). When compared with baseline, differences in the weekly warfarin dose reached statistical significance when all 12 weeks of follow-up were included (34 ± 13.8 mg vs 32 ± 15.5 mg; P = .01) but were not statistically significant when analyzed 4 to 12 weeks after the bleeding event. CONCLUSIONS: Our observations suggest that bleeding can result in an elevated INR in patients previously stable on warfarin.

Effect of high-dose cranberry juice on the pharmacodynamics of warfarin in patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Case reports suggest an association between cranberry juice and potentiation of warfarin. Studies using 240 ml of cranberry juice daily demonstrated no interaction. It is unknown if higher amounts of cranberry juice will interact with warfarin. WHAT THIS STUDY ADDS: Cranberry juice at 240 ml twice daily does not alter the pharmacodynamics of warfarin. AIM: To determine if high-dose cranberry juice (240 ml twice daily) alters the pharmacodynamic action of warfarin. METHODS: Ten male patients taking stable doses of warfarin were given cranberry juice at 240 ml twice daily for 7 days. Prothrombin times were drawn at baseline and days 2, 6 and 8 after administration of the juice. Prothrombin times were averaged for each day and mean times were compared from each study day to baseline using repeated measures ANOVA. RESULTS: There was no statistical difference between mean prothrombin time at baseline and any day tested during juice administration. CONCLUSIONS: Cranberry juice (240 ml twice daily for 1 week) did not alter the pharmacodynamics of warfarin in patients.

Comparing hyperlipidemia control with daily versus twice-weekly simvastatin.

BACKGROUND: Costs associated with the use of hydroxymethylglutaryl coenzyme A reductase inhibitors are increasing. Finding ways to manage hyperlipidemia at lower costs is critical to all healthcare systems. OBJECTIVE: To assess effectiveness, safety, cost, and patients' satisfaction when converting hyperlipemic patients taking simvastatin daily to simvastatin twice weekly. METHODS: This nonrandomized, open-label, proof-of-concept study converted patients treated with simvastatin 10 or 20 mg daily to 40 or 80 mg twice weekly, respectively, for 12 weeks. The lipid profiles at enrollment, week 6, and week 12 were compared using repeated-measures ANOVA. The percentage of patients attaining the appropriate low-density lipoprotein cholesterol (LDL-C) goal was determined. RESULTS: Thirty-one patients completed the study. The proportion of patients at the LDL-C goal was not statistically different between enrollment and week 12 (87% vs 68%; p = 0.068). The mean LDL-C value +/- SD at weeks 6 and 12 increased compared with enrollment (112 +/-20, 111 +/-17, and 97 +/- 17 mg/dL, respectively; p < 0.001). Three (10%) patients reported nonadherence to the twice-weekly regimen. Seventeen (55%) patients reported that both regimens were equally convenient or preferred the twice-weekly regimen. Estimated cost-savings at our institution associated with this regimen would be $32 000 per 1000 patients per year. CONCLUSIONS: The twice-weekly regimen safely maintained most of the patients at their LDL-C goal level, and over half the patients found this regimen to be the same or easier to follow than a daily regimen. Large outcome studies evaluating this approach are needed.

Low-Dose Aspirin and Ibuprofen Reduce the Cutaneous Reactions Following Niacin Administration.

BACKGROUND: Moderate doses of prostaglandin inhibitors may reduce the cutaneous reactions from niacin administration. We undertook this study to determine if low doses of either ibuprofen or aspirin reduces cutaneous reactions from niacin in healthy volunteers. METHODS: Twenty-two subjects were randomized to received crystalline niacine 500 mg preceded by either placebo, aspirin 165 mg, aspirin 325 mg, or ibuprofen 200 mg. The study was crossover and double blinded, and treatment arms were separated by 2 days. Subjects were asked to rate the severity of flushing, itching, and tingling after niacin on a visual analog scale (0---no symptoms; 10---severe symptoms). Statistical analysis was performed using repeated measures of analysis of variance. RESULTS: Nineteen of the 22 subjects completed the protocol. Overall, aspirin 325 mg statistically reduced flushing after niacin administration. No statistical difference was observed for the other treatment arms for either flushing, itching, or tingling. When subjects experiencing the worse symptoms were analyzed separately, all treatment arms statistically reduced the flushing, itching, or tingling from niacin. Aspirin 325 mg was the most efficacious, followed by aspirin 165 mg and ibuprofen 200 mg. CONCLUSION: These data demonstrate that pretreatment with low doses of aspirin or ibuprofen are effective in reducing cutaneous reactions from niacin administration.