Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Abbott, AstraZeneca, Boehringer Ingelheim, Daiichi, Sankyo, Forest Pharmaceuticals, Lilly, Novo Nordisk, Takeda.
Spironolactone may save the day with resistant hypertension
Source: Engbaek M, et al. The effect of low-dose spironolactone on resistant hypertension. J Am Soc Hypertens 2010;4:290-294.
Although the definition of resistant hypertension (r-HTN) has some variation, in the United States it is most commonly defined as inability to achieve target blood pressure with optimized doses of three antihypertensive agents, including a diuretic. Depending on the population studied, as many as 15%-18% of subjects entering clinical trials who presumably receive some of the best care medicine has to offer are ultimately determined to have r-HTN.
Spironolactone (SPIR) is an aldosterone antagonist with modest diuretic activity. It has been shown to be effective in reducing blood pressure independent of aldosterone status; that is, one does not have to be a "high aldosterone" subject to enjoy meaningful BP reduction.
Engbaek et al report on 344 r-HTN subjects (mean BP 169/88, while already on three other medications), who were treated with SPIR 25 mg or 50 mg QD. They found a prompt and sustained mean BP reduction with SPIR: a 17/7 mm Hg reduction at 1 month, 24/10 mm Hg reduction at 3 months, and 26/11 mm Hg reduction at 6 months, all of which were statistically significant. The two most predictable adverse effects of SPIR, hyperkalemia and gynecomastia, were infrequent: 4.1% and 5.2%, respectively. Other clinical trials corroborate the utility and tolerability of SPIR to manage r-HTN. Clinicians should be reassured that < 10% of participants discontinued SPIR secondary to adverse events.
Treating venous thromboembolism with rivaroxaban
Source: The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-2510.
The treatment of acute venous thromboembolism commonly is managed successfully with enoxaparin followed by intermediate to long-term prevention of recurrent thromboembolism with warfarin.
Despite a proven track record of efficacy, warfarin has limitations, including the need for ongoing monitoring, problematic interactions with medications and food, and risk of significant bleeding, which occurs in 1%-2% of patients using long-term warfarin.
Rivaroxaban is a direct factor X inhibitor administered orally once daily. It is effective both acutely (hence, it may be utilized instead of heparin during the acute phase of venous thromboembolism) and chronically. Because it does not have any interactions with food and does not require monitoring, it provides many fewer obstacles to successful patient management than warfarin or heparin-warfarin combinations.
The EINSTEIN Investigators reported on two trials: One compared rivaroxaban with enoxaparin + warfarin for acute venous thromboembolism (n = 3449), and the other compared rivaroxaban with placebo in subjects who had completed 6 months of warfarin treatment for DVT.
For acute venous thromboembolism, rivaroxaban was non-inferior to enoxaparin + warfarin. In the long-term trial, rivaroxaban was superior to placebo. Rivaroxaban appears to provide an attractive alternative treatment for venous thromboembolism.
Fish oils: Where's the beef?
Source: Kromhout D, et al. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 2010;363:2015-2026.
Observational data indicate that populations with high intake of fish oil have less cardiovascular disease (CVD) endpoints, spurring clinical trials to elucidate the relationship. A 2008 meta-analysis suggested that in persons with existing coronary heart disease (CHD), supplements of fish oils (n-3 fatty acids, e.g., eicosapentaenoic acid and docosahexaenoic acid) reduced CHD mortality by as much as 20%. This beneficial effect has been attributed to a reduced vulnerability to arrhythmia provided by fish oils; disappointingly, the inclusion of fish oil supplements in study subjects with implantable cardioverter-defibrillators did not confirm an anti-arrhythmic effect.
To clarify the potential role of fish oil supplementation for CHD patients, the Alpha Omega Trial enrolled men and women age 60-80 with a history of myocardial infarction (n = 4837). Study subjects were randomized to fish oil supplementation or placebo for 40 months.
Fish oil supplementation did not provide a statistically significant reduction in CVD events. Because many of the study subjects were receiving other interventions to reduce CVD risk (e.g., statins, antiplatelet agents, BP drugs), the authors posit that it is possible that these results, which are divergent from earlier trials, reflect the lesser available margin for improvement in persons already receiving other good tools for CVD risk reduction.
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