Antihypertensive therapy

The "silent killer" - still at large

Most Americans over age 60 have hypertension. Even among those whose blood pressures are normal at age 55, the lifetime risk of hypertension is 90%.¹ 

Despite availability of dozens of effective treatments and decades of data, less than 2/3 of patients in the U.S. with hypertension are receiving treatment, and less than 1/2 are adequately controlled.² In hypertensive patients, achieving a 12 mmHg reduction in systolic blood pressure (SBP) over 10 years will prevent 1 death for every 11 patients treated, making this one of the most powerful tools a physician can use to prevent devastating illness and disability.³

Begin with lifestyle changes

Some patients may be able to control their blood pressure with improved diet, reductions in salt or alcohol, weight reduction, and exercise. These measures are key components of management for nearly all patients.

When a drug is needed...

Many antihypertensive medications are available, but direct comparisons between classes were scarce prior to the ALLHAT study.⁵ This trial was an NIH-supported head-to-head randomized comparison of common treatment choices in >42,000 patients with hypertension: a thiazide-like diuretic (chlorthalidone), a calcium channel blocker (CCB: amlodipine [Norvasc]), an ACE inhibitor (ACEI: lisinopril), and an alpha-blocker (doxazosin [Cardura]).

Highlights from the ALLHAT trial⁵

• Thiazides achieved better systolic blood pressure control and as good or better health outcomes, compared to the other drugs studied - and they were just as well-tolerated.
• Thiazides were superior to CCBs and ACEIs in preventing congestive heart failure.
• Thiazides were superior to ACEIs in preventing cardiovascular events.
• Thiazides were superior to alpha-blockers in preventing cardiovascular events, including both CHF and coronary artery disease.

Good drugs with a bad rap

Some physicians are reluctant to prescribe thiazides because of concern over side effects such as hypokalemia. However, much of the bad reputation of thiazides arose in earlier times, when excessively high doses were used. At moderate doses (e.g., 12.5 mg hydrochlorothiazide [HCTZ]), they provide very effective blood pressure control, with a rate of side effects no higher than other anti-hypertensives, and only 2% higher than placebo.

Back to basics

The Joint National Committee on Hypertension (JNC), funded by the NIH, is the nation's premier authority on blood pressure treatment. Its most recent guidelines emphasize the central role of thiazides in the management of hypertension.When used in low doses, thiazides are very effective, very well-tolerated, and inexpensive.

JNC has identified specific co-existing conditions as "compelling indications" for the addition or use of other drug classes, such as ACEIs and beta-blockers (BBs). These include diabetes, coronary artery disease, and congestive heart failure.

When to treat and how

• In general, blood pressure should be maintained at 140/90 or less, or less than 130/80 in patients with diabetes or chronic kidney disease.
• Start with a thiazide unless there is a compelling indication to use a different drug. 
• Most regimens requiring two or more drugs should include a thiazide diuretic, unless there is a contraindication.

Once you've chosen the right class, does it matter which individual drug you use?

There is very little data suggesting that any one agent within a drug class (e.g., ACEIs) is superior to another in that class. Only a few trials have directly compared drugs within a class heat-to-head, and most studies have just assessed blood pressure control and safety. These studies suggest that in general, all agents within a given drug class are equally effective and equally safe. There can, however, be substantial differences in cost between agents in the same class.

Combination therapy

Even at high doses, most drug classes will lower blood pressure by 9-10 mmHg. Therefore, for some patients, achieving adequate hypertension control may require more than one medication. In fact, only about one-quarter of patients will have good BP control on only one drug. Combination therapy with moderate doses of agents from multiple classes can provide additive effects on blood pressure without increasing the risk of adverse events from high doses of individual drugs. Most combinations are safe, except for beta blocker/CCB combinations (risk of bradycardia) and ACEI/ARB combinations (risk of hyperkalemia, hypotension, syncope, and renal dysfunction.

The choice of combination therapy for hypertension should be guided by the JNC 7 guidelines:⁴

• Thiazides should be a part of most multi-drug regimens.
• The choice of other medications should be driven by compelling indications

Many antihypertensive combinations can be prescribed as a single pill in a once-daily generic form, allowing for simpler and more affordable regimens. Combinations of hydrochlorothiazide (HCTZ) and generic ACEIs are especially appealing.

From initial treatment to control

Most patients with hypertension do not achieve adequate blood pressure control. The two main reasons are poor compliance by the patient and failure to intensify treatment by the physician.

Patient compliance

Up to half of patients stop their antihypertensive medications after only a short time-and many patients never even fill the first prescription. Improving patients' adherence to their prescribed regimens is an effective way to improve blood pressure control.

What works to promote compliance?

• Make the regimen as simple as possible.
• Be sure you prescribe the most affordable medications.
• Ask the patient if he or she is having difficulty taking the prescribed medications.

At each visit, re-educate the patient about the importance of controlling blood pressure.

Overcoming inertia

Even with good compliance, adequate blood pressure control often requires multiple agents. In many cases, "clinical inertia" can impede the addition of additional antihypertensive medications.⁶ Physicians must be willing to add medication when blood pressure is not adequately controlled.

Stopping the "silent killer"

Effective hypertension control is one of the best ways a physician can make a real difference in patients' health by preventing myocardial infarction, stroke, renal damage, and premature death.

Several key steps to improve management:

• Low-dose thiazides should play a central role as initial therapy for many patients, and as part of combination treatment for others.
• Choose other medications based on compelling indications.
• Combination therapy will often be needed.
• When choosing agents, consider cost, simplicity, and compliance.

This material was produced by Niteesh K. Choudhry, M.D., Ph.D., Assistant Professor of Medicine, Michael Fischer, M.D., M.S., Assistant Professor of Medicine,Leslie Jackowski, B.Sc. (Hon.), M.B.B.S., Senior Clinical Consultant, Danielle Scheurer, M.D., M.Sc., F.H.M., Assistant Professor of Medicine, and William H. Shrank, M.D., M.S.H.S., Assistant Professor of Medicine, Harvard Medical School. Senior editor: Jerry Avorn, M.D., Professor of Medicine, Harvard Medical School. Drs. Avorn, Choudhry, Fischer, and Shrank are physicians at the Brigham and Women's Hospital in Boston. None of the authors accepts any personal compensation from any drug company.

These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient's clinical condition.

References:

1. Vasan, R.S., et al., Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. Jama, 2002. 287(8): p. 1003-10.
2. Wong ND, et al. Inadequate control of hypertension in US adults with cardiovascular disease comorbidities in 2003-2004. Arch Intern Med 2007;167(22):2431-6.
3. Ogden, L.G., et al., Long-term absolute benefit of lowering blood pressure in hypertensive patients according to JNC VI risk stratification. Hypertension 2000; 35(2):539-43.
4. Joint National Committee on Prevention Detection, Evaluation, and Treatment of High Blood Pressure. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure - Complete Report. JNC 7 Complete Report: The Science Behind the New Guidelines. National Institutes of Health, National Heart, Lung, and Blood Institute. NIH Publication No. 04-5290. 2004. Obtained June 2010 from: http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm.
5. The ALLHAT Collaborative Research Group. Sponsored by the Narional Heart, Lung, and Blood Institute (NHLBI). Major outcomes in high risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic. JAMA; 2002:2981-2997. Obtained April 2007 from: http://allhat.uth.tmc.edu/Slides/Results.ppt.
6. Phillips, L.S., et al., Clinical inertia. Ann Intern Med, 2001. 135: p. 825-834.