Cochrane for Clinicians

Putting Evidence into Practice

Are Beta Blockers Effective First-line Treatments for Hypertension?

WILLIAM E. CAYLEY, JR., md, University of Wisconsin Eau Claire Family Medicine Residency, Eau Claire, Wisconsin

The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Dr. Cayley presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a critique of the review. The practice recommendations in this activity are available at http://www.cochrane.org/reviews/en /ab002003.html.

Clinical Scenario

A 55-year-old woman presents with new-onset hypertension.

Clinical Question

Should beta blockers be used as first-line treatments for lowering blood pressure?

Evidence-Based Answer

Current evidence does not support the use of beta blockers as initial therapy for hypertension.

Practice Pointers

To reduce rates of stroke and coronary heart disease, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends reducing blood pressures to 140/90 mm Hg in the general population and to 130/80 mm Hg in patients with diabetes or chronic kidney disease.1 If patients do not meet blood pressure goals with lifestyle modifications, thiazide diuretics are recommended as first-line pharmacotherapies. Other antihypertensive medications are recommended if certain "compelling indications" are present: beta blockers for coronary heart disease with angina, beta blockers and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for heart failure, and ACE inhibitors or ARBs for diabetes.1

Two recent meta-analyses found that atenolol (Tenormin) was less effective than other antihypertensives at reducing stroke2 and overall cardiovascular outcomes,3 calling into question the role of beta blockers in the primary treatment of hypertension. This Cochrane review found that the highest-quality evidence on the effect of beta blockers on patient-oriented outcomes such as morbidity and mortality is mainly from studies of atenolol in North American and Western European populations.4

Overall, the reviewed studies failed to provide support for the use of beta blockers. Although beta blockers were no better or worse than diuretics, they were inferior to calcium channel blockers in reducing risk of mortality or total cardiovascular disease and were inferior to ACE inhibitors or ARBs and calcium channel blockers in reducing risk of stroke. The only findings favoring beta blockers showed that they were superior to placebo in reducing risk of stroke and total cardiovascular disease. Table 1 compares beta blockers with other antihypertensive medications.4

Table 1. Beta Blockers vs. Other Antihypertensives for Improving Patient-Oriented Outcomes
	Outcomes
Comparison antihypertensive	Total mortality	Coronary heart disease	Stroke	Total cardiovascular disease
Placebo	No difference	No difference	Beta blockers superior (NNT = 200)	Beta blockers superior (NNT = 140)
Diuretics	No difference	No difference	No difference	No difference
Calcium channel blockers	Beta blockers inferior (NNH = 200)	No difference	Beta blockers inferior (NNH = 180)	Beta blockers inferior (NNH = 80)
ACE inhibitors or ARBs	No difference	No difference	Beta blockers inferior (NNH = 65)	No difference
NNT = number needed to treat; NNH = number needed to harm; ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker. Information from reference 1.

Lifetime risk of coronary heart disease and stroke is directly related to higher blood pressure5; therefore, the primary reason for treating hypertension is to reduce morbidity and mortality from these conditions. Generic beta blockers are inexpensive and may seem appealing as initial antihypertensive therapy; however, this Cochrane review supports the JNC 7 recommendation to begin medical treatment of high blood pressure with thiazide diuretics. ALLHAT (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) demonstrated that thiazide diuretics are as effective as calcium channel blockers and ACE inhibitors for reducing cardiovascular risk.6

Address correspondence to William E. Cayley, Jr., MD, bcayley@yahoo.com. Reprints are not available from the author.

Author disclosure: Nothing to disclose.

REFERENCES

1. Wiysonge CS, Bradley H, Mayosi BM, Maroney R, Mbewu A, Opie LH, et al. Beta-blockers for hypertension. Cochrane Database Syst Rev 2007;(1):CD002003.

2. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al., for the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206-52.

3. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005;366:1 545-53.

4. Khan N, McAlister FA. Re-examining the efficacy of beta-blockers for the treatment of hypertension: a meta-analysis [Published correction appears in CMAJ 2007;176:976]. CMAJ 2006;174:1737-42.

5. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, for the Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies [Published correction appears in Lancet 2003;361:1060]. Lancet 2002;360: 1903-13.

6. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) [Published corrections appear in JAMA 2003;289:178, and JAMA 2004;291:2196]. JAMA 2002;288:2981-97.

Cochrane Briefs

Effectiveness of Insulin Sensitizing Drugs for Polycystic Ovary Syndrome

Clinical Question

Do insulin sensitizing drugs with or without oral contraceptive pills improve clinical outcomes in women with polycystic ovary syndrome (PCOS)?

Evidence-Based Answer

Insulin sensitizing drugs are more effective than oral contraceptives alone at improving fasting insulin levels in patients with PCOS. Compared with metformin (Glucophage) alone, oral contraceptives alone better control irregular menstrual cycles and reduce androgen levels. There is insufficient evidence to recommend insulin sensitizing drugs alone or in combination with oral contraceptives to decrease the risk of diabetes, cardiovascular disease, or endometrial cancer.

Practice Pointers

PCOS is defined by the presence of two of the following criteria: oligomenorrhea or amenorrhea, clinical or biochemical hyperandrogenism, or polycystic ovaries visible on ultrasonography. Family physicians routinely treat symptoms of irregular menstrual cycles and excessive androgen levels with combination oral contraceptives. The benefit of using insulin sensitizing drugs is unclear. Ideally, treatment of PCOS would improve clinical symptoms such as hirsutism and infertility and decrease the risk of type 2 diabetes, cardiovascular disease, or endometrial cancer.

In this Cochrane review, the authors searched the literature for randomized controlled trials (RCTs) comparing treatment of PCOS with insulin sensitizing drugs with or without oral contraceptives. They found six RCTs that included 226 total patients, 20 to 52 years of age. Patients were followed for four to 12 months, with a median study duration of six months. Metformin, 500 mg orally three times per day, was the only insulin sensitizing drug studied.

Oral contraceptives were more effective at improving menstrual cycle regularity and lowering androgen levels compared with metformin. Although these findings were statistically significant, only 104 participants in three trials were analyzed for these outcomes. Metformin lowered fasting insulin levels and did not impact triglyceride levels compared with oral contraceptives. However, metformin did not lower fasting glucose levels in patients without impaired glucose tolerance and did not reduce the risk of type 2 diabetes when used alone. Combined therapy improved hirsutism in a single RCT with 34 participants.

No combined RCTs with acne as primary outcome were available. None of the trials analyzed the primary outcomes of stroke, myocardial infarction, or endometrial cancer.

This review was limited by small study sizes. Because outcomes addressed chronic disease, the studies may not have followed patients long enough to show prevention benefits. No studies were available comparing alternative insulin sensitizing drugs such as rosiglitazone (Avandia) or pioglitazone (Actos). There was insufficient evidence on the outcomes of hirsutism, acne, body mass index, blood pressure, and other cholesterol parameters.

Evaluating fertility rates as a primary outcome could provide practice-modifying information for many physicians. Expert consensus by the American Association of Clinical Endocrinologists states that metformin should be considered in the initial treatment of PCOS, especially for patients who are overweight or obese.1 The 2002 American College of Obstetricians and Gynecologists guideline recommends metformin as one measure to improve ovulatory frequency and to treat risk factors for diabetes and cardiovascular disease.2

HOLLIS JULSON, MD

Source: Costello M, Shrestha B, Eden J, Sjoblom P, Johnson N. Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Cochrane Database Syst Rev 2007(1):CD005552.

Author disclosure: Nothing to disclose.

REFERENCES

1. Polycystic Ovary Syndrome Writing Committee. American Association of Clinical Endocrinologists position statement on metabolic and cardiovascular consequences of polycystic ovary syndrome. Endocr Pract 2005;11:125-34.

2. American College of Obstetricians and Gynecologists. Clinical management guidelines for obstetrician-gynecologists. ACOG practice bulletin, no. 41. Obstet Gynecol 2002;100:1389-402.

This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). See CME Quiz on page 1277.

The series coordinator for AFP is Clarissa Kripke, MD, Department of Family and Community Medicine, University of California, San Francisco.

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