Pharmacology Watch: Meta-analysis Compares Antihypertensive Classes
Meta-analysis Compares Antihypertensive Classes
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In this issue: Comparing blood pressure medications, determining optimal length of androgen-deprivation therapy, red yeast rice for LDL reduction, and FDA Actions.
Comparison of antihypertensive classes
All classes of antihypertensive drugs are equivalent in preventing CHD and stroke according to a British study. In the largest meta-analysis of randomized trials of blood pressure reduction to date, researchers reviewed the efficacy of the 5 major classes of blood pressure medications (thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and calcium-channel blockers). Beta-blockers were found to have a special effect over and above that of blood pressure reduction in preventing recurrent CHD events in people with a history of CHD (29% risk reduction vs 15% with other drugs), although this affect was limited to a few years after myocardial infarction. Otherwise, the 5 main classes and blood pressure-lowering drugs were similarly effective in preventing CHD events and strokes, with the exception of calcium-channel blockers, which have a slightly higher benefit in preventing stroke (relative risk, 0.92; 95% confidence interval, 0.85-0.98). There was benefit in reducing risk of CHD and stroke with BP-lowering treatment regardless of the patient's pretreatment blood pressure, surprisingly even as low as 110 mmHg systolic and 70 mmHg diastolic. Treatment with blood pressure-lowering medications was also associated with a 13% reduction in all-cause mortality, although there was no reduction in cancer or nonvascular related deaths. The authors conclude that blood pressure lowering is important in everyone over a certain age regardless of pretreatment blood pressure and that all classes of blood pressure medications had similar effective in reducing CHD events and stroke (BMJ 2009;338:b1665).
Length of androgen-deprivation therapy
Men with locally invasive prostate cancer who have received external beam radiation do better with 3 years of androgen-deprivation therapy compared to 6 months of therapy according to a new study from Europe. After receiving radiation therapy, 970 men were randomly assigned to 6 months of androgen suppression (n = 483) vs 3 years of suppression (n = 487). After mean follow-up of 6.4 years, 132 patients in the short-term group and 90 patients in the long-term group had died. The number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The 5-year overall mortality was 19% vs 15.2% for short-term and long-term suppression, respectively, with an observed hazard ratio of 1.42 (P = 0.65 for non-inferiority). The authors conclude that the combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiation therapy plus 3 years of androgen suppression in men with locally advanced prostate cancer (N Engl J Med 2009;360:2516-2527). In an accompanying editorial, Peter Albertson, MD, points out the importance of determining the optimal length of androgen-deprivation therapy because of long-term side effects including weight gain, fatigue, hot flushes, osteoporosis, cardiac disease, and depression. With the high level of regular screening for prostate cancer, most men are diagnosed earlier with much lower grade disease than those addressed in this study, and it is unclear whether these findings can be applied to these men with clinically localized cancer. Radiation plus or minus androgen deprivation vs surgery, age of the patient at diagnosis, and staging of the tumor all are important in determining therapy (N Engl J Med 2009;360:2572-2574).
Red yeast rice and LDL
Patients may be asking about red yeast rice for the treatment of hypercholesterolemia because of a recent study in the Annals of Internal Medicine. Patients were recruited from a cardiology practice in suburban Philadelphia who had had a history of statin-associated myalgias. Thirty-one patients were randomized to receive red yeast rice 1800 mg or placebo twice daily for 24 weeks. All patients were also enrolled in a 12-week therapeutic lifestyle program. Red yeast rice was effective in lowering LDL-cholesterol an average of 43 mg/dL from baseline at week 12 and 35 mg/dL at week 24 compared to reductions of 11 mg/dL at week 12 (P < 0.001) and 15 mg/dL at week 24 (P = 0.011) in the lifestyle-only group. Total cholesterol was also lowered in the treatment group, although there was no change in HDL-cholesterol or triglycerides. Treatment with red yeast rice was not associated with changes in liver enzymes or CPK levels and there was no difference in weight loss or pain severity scores between the two groups. The authors conclude that red yeast rice and therapeutic lifestyle change decreased LDL-cholesterol without increasing CPK or pain levels in patients with a history of statin-related myopathy (Ann Intern Med 2009;150:830-839).
The study is interesting because of the large number of patients who do not tolerate statins due to muscle pain and weakness. These patients frequently experience myalgias without myositis (normal CPK levels), and the majority continue to have symptoms despite dose adjustments or changing to a different statin. Red yeast rice is a Chinese supplement known to contain naturally occurring lovastatin (monocolin K) and other monocolins that inhibit HMG-CoA reductase, the same enzyme targeted by statins. It is unclear why red yeast rice is better tolerated than commercial statins, but the authors suggest it may be due to the relatively low dose of the statin, or other, yet undiscovered properties of red yeast rice. The authors also point out that since red yeast rice is a supplement, the chemical composition of different manufacturers is problematic and that patients should be monitored while taking the product. These findings beg the question whether low-dose generic lovastatin may be equally well tolerated, but future studies may help determine if red yeast rice has unique properties that make it an option for the many patients who do not tolerate statins and need to lower cholesterol. In 2007, the FDA issued a warning to consumers to avoid red yeast rice because it contains a pharmaceutical drug, though most products marketed in this country contain negligible amounts of lovastatin.
FDA Actions
The FDA has alerted consumers that 3 Zicam® products may result in long-lasting or permanent loss of smell (anosmia). Zicam Cold Remedy Nasal Gel, Zicam Cold Remedy Nasal Swabs, and Zicam Cold Remedy Swabs Kids Sized are all implicated, and the FDA is recommending that consumers stop using the products and throw them away. All 3 of these products contain zinc, which has not been shown to be effective in reducing the duration or severity of cold symptoms. Other Zicam oral tablets and lozenges have not been included in this advisory. Matrixx Initiatives, the manufacturer of Zicam, is offering refunds for the 3 products noted above. The company is also withdrawing the two adult products from the market — Cold Remedy Swabs Kids Sized had been previously withdrawn. There have been more than 130 reports of anosmia associated with intranasal Zicam product use ranging from 1 dose to long-term use.
The FDA has approved the first formulation of parenteral ibuprofen to treat fever and pain in hospitalized patients. The drug is given intravenously over 30 minutes in doses of 400-800 mg every 6 hours as needed for pain; lower doses are indicated for fever. As with all NSAIDs, caution is warranted when using injectable ibuprofen in patients with heart failure, renal dysfunction, increased risk for thrombosis, or history of ulcers or GI bleeding. Injectable ibuprofen is marketed by Cumberland Pharmaceuticals as Caldolor™.
This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5468. E-mail: [email protected].
In this issue: Comparing blood pressure medications, determining optimal length of androgen-deprivation therapy, red yeast rice for LDL reduction, and FDA Actions.Subscribe Now for Access
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