Archives of Drug Information最新文献

Background. Hypertension in blacks imposes a greater left ventricular hypertrophy, and accelerated heart failure onset. We evaluated and compared the echocardiographically determined systolic and left ventricular diastolic functional indices in Nigerian hypertensive patients, associated with the chronic use of ACE inhibitors, Calcium channel blockers (CCB) or their combinations.

Methods. Ejection fraction -EF, intraventricular relaxation time (IVRT), E/A peak velocity ratio, E wave deceleration time] as well as the left ventricular mass index (LVMI) was undertaken among 41 Nigerian patients with essential hypertension only, on treatment for 4–6 months prior. The 41 patients (aged 59 ± 10 years, 40% females) were divided into three groups; those receiving (i) ACE inhibitors; or (ii) CCB or (iii) combination of ACEI and CCB. All the three groups had a background of diuretic treatment for optimal blood pressure control.

Results. There were no statistically significant differences in the mean LVMI or sitting blood pressure between treatment groups. E/A ratio for ACEI treatment was 1.06 ± 0.44, CCB 0.74 ± 0.19, and for ACEI + CCB 0.87 ± 0.26 (F = 3.29, P = 0.048 anova). The 95% confidence interval for the E/A ratio on ACEI was 0.8 to 1.33. The A wave duration time integral (AVVTi) were all abnormally large, but showed a significant between treatment group difference (P = 0.037, anova). The values were 21.9 ± 4.7 for ACEI, 25.3 ± 6.3 for CCB, and least at 20.1 ± 3.6 cm for the ACE + CCB combination. Similarly, the IVRT was lowest and <100 ms with ACEI + CCB being 93 ± 18 ms, ACEI 115 ± 23 ms, and CCB being 117 ± 22 ms (F = 4.92, P = 0.01, anova). The 95% CI for IVRT on ACEI + CCB was 82 to 104 ms. There were no between treatment group differences in systolic contractility, (fractional shortening or EF).

Conclusions. The results indicate that use of an antihypertensive drug regime inclusive of an ACE inhibitor (±CCB) may be associated with greater salutary effect on indices of diastolic function, (E/A > 1, lower AVVTi, IVRT < 100 ms) even in the presence of an equivalent effect on systolic function and blood pressure.

Objectives. Selective cyclooxygenase (COX)-2 inhibitors are effective analgesic and anti-inflammatory agents with improved gastrointestinal safety and tolerability compared with traditional NSAIDs. However, data from long-term, placebo-controlled studies have shown an increased risk of thrombotic cardiovascular (CV) events for COX-2 inhibitors. Changes in levels of CV biomarkers are potentially useful surrogate measures of pathologic changes associated with CV risk.

Methods. We randomized 433 patients with osteoarthritis to etoricoxib 90 mg once daily, celecoxib 200 mg twice daily, ibuprofen 800 mg three times daily, or placebo for 12 weeks. The hypothesis was that etoricoxib would be non-inferior or superior to placebo in effect on C-reactive protein (CRP), LDL-cholesterol, homocysteine, and fibrinogen.

Results. Relative to placebo, etoricoxib was noninferior for effect on CRP (decreased 7.8% vs. placebo; 97.5% CI of the difference: −30.5, 22.4), LDL-C (−4.0% vs. placebo; 97.5% CI: −10.6, 3.2), homocysteine (−3.9% vs. placebo; 97.5% CI: −11.6, 4.6), and fibrinogen (−3.7% vs. placebo; 97.5% CI: −9.4, 2.3). Etoricoxib was not different from placebo, celecoxib, or ibuprofen for any biomarker.

Conclusion. Etoricoxib was comparable to placebo, celecoxib, and ibuprofen for effects on the CV risk markers measured.

Objective. C-reactive protein (CRP) and homocysteine are markers of cardiovascular risk that may have inflammatory effects. HMG coenzyme A reductase inhibitors (statins) have anti-inflammatory effects in vitro, but it is not clear if such responses in vivo are secondary to lipid lowering. We examined the hypothesis that CRP and homocysteine would stimulate cytokine release in human whole blood and that short-term treatment with a statin would inhibit it.

Methods. The time course of IL-6 and MCP-1 production was determined in whole blood incubated with saline, 1 µg/mL lipopolysaccaride (LPS), 50 and 100 µM/L DL-homocysteine, and 5 µg/mL human recombinant CRP for 24 hours at 37°C under 5% CO₂ atmosphere. Cytokine responses were determined in blood drawn from 15 healthy volunteers before and after administration of pravastatin 40 mg daily for 2 days.

Results. Both human recombinant CRP and LPS significantly increased the production of IL-6 and MCP-1 in whole blood samples more than 4-fold (P < 0.001) but homocysteine did not. Oral administration of pravastatin, 40mg daily for 2 days, decreased CRP-stimulated IL-6 production by approximately 20% (P = 0.02) 6 hours after incubation, but did not affect MCP-1 production (P = 0.69). Pravastatin treatment did not affect LPS-stimulated MCP-1 but increased IL-6 modestly.

Conclusions. CRP stimulated the production of the proatherogenic mediators MCP-1 and IL-6 in human whole blood, but homocysteine did not. CRP-stimulated production of IL-6, but not MCP-1, was modestly attenuated by short-term treatment with pravastatin.

Objectives. Cardiovascular risk is increased in patients with systemic lupus erythematosus (SLE). Drugs used to treat SLE can modify traditional cardiovascular risk factors. We examined the effect of selected drugs used in the treatment of SLE on cardiovascular risk factors.

Methods. We compared systolic and diastolic blood pressure, serum lipid concentrations, glucose, homocysteine, and urinary F₂-isoprostane concentrations in 99 patients with lupus who were either current users or non-users of systemic corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 selective NSAIDs, azathioprine, and methotrexate. Multivariable adjustment was done with linear regression modeling using sex, age and disease activity (SLEDAI) as controlling variables.

Results. Serum triglyceride concentrations were higher (135.1 ± 61.4 vs. 95.3 ± 47.5 mg/dL, adjusted P = 0.003) in patients receiving corticosteroids. Homocysteine concentrations were marginally higher in patients receiving methotrexate (adjusted P = 0.08). Current use of either NSAIDs or COX-2 inhibitors was not associated with increased cardiovascular risk factors. Current hydroxychloroquine use was not associated with significant alterations in lipid profiles.

Conclusions. In a non-random sample of patients with SLE, current corticosteroid use was associated with increased triglyceride concentrations, but other drugs had little effect on traditional cardiovascular risk factors.

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