Antihypertensive therapy

The "silent killer" - still at large

Most Americans over age 60 have hypertension, and the risk increases as patients age. Even those with normal blood pressure at age 55 have a lifetime risk of hypertension of 90%.1

Despite availability of dozens of effective treatments and decades of data, only about 1 in 3 people with hypertension in the U.S. is adequately controlled.1

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, without a lifetime of drug therapy. Nearly all patients will benefit from lifestyle modifications.

When a drug is needed...

Many antihypertensive medications are available, but direct comparisons between classes have been scarce. To fill this void, the NIH supported the ALLHAT study: a head-to-head trial of 33,357 patients randomly assigned to receive thiazide-like diuretics, calcium channel blockers, ACE inhibitors, or alpha-blockers.2

Main results of the ALLHAT trial2

  • Thiazide-like diuretics 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 calcium channel blockers (by about one-fourth) in preventing heart failure.
  • Thiazides were superior to ACE inhibitors in preventing cardiovascular events.
  • Thiazides were superior to alpha-blockers in preventing cardiovascular events, including both heart failure and other coronary artery disease.

Good drugs with a bad rap

Many physicians have been reluctant to prescribe thiazides because of concern over side effects such as hypokalemia. Much of the drugs' bad reputation arose in earlier times, when excessively high doses were used. At low doses (e.g., 12.5 mg HCTZ), thiazides:

  • provide effective blood pressure control
  • have a rate of side effects only 2% higher than in placebo patients - the same as other classes of antihypertensives3

Back to basics

The Joint National Committee on Hypertension (JNC), representing independent scientists and funded by the National Institutes of Health, is the nation's premier authority on blood pressure treatment. Its most recent guidelines recommend starting a thiazide for most patients with uncomplicated hypertension.1 When used in low doses, thiazides are very effective, very well-tolerated, and affordable.

Other drug classes, such as ACE inhibitors and beta-blockers, are key parts of hypertension treatment for patients with compelling indications, such as diabetes and congestive heart failure.

When to treat and how

  • In general, maintain blood pressure at 140/90 or less, or 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. Compelling indications include:
    • diabetes, heart failure or chronic kidney disease: use an ACE inhibitor
    • coronary artery disease: use a beta-blocker
  • Most regimens requiring two or more drugs should include a thiazide, unless there is a contraindication.

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

Although drugs that belong to one class (e.g., ACE inhibitors) can have pharmacologic differences, there is very little data suggesting that any one agent within a drug class is superior to another.

Few trials have directly compared drugs within a class "heat-to-head" and measured clinically important outcomes such as death or myocardial infarction; 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 are, however, substantial differences in cost between agents.

From initial treatment to control

Most patients prescribed antihypertensive medications do not achieve adequate blood pressure control. The two main reasons:

  • poor compliance by the patient
  • lack of treatment intensification by the physician

Up to 50% of patients stop their antihypertensive medications after only a short time - and many patients never even begin taking them. Improving patients' adherence to their medications is a key way to improve blood pressure control.

What works to promote compliance?

  • simple dosing regimens (once a day if possible)
  • affordable medications
  • patient education

Combination therapy

Even at high doses, most individual drug classes will lower blood pressure by 10-12 mmHg. Therefore, for some patients, getting full hypertension control may require more than one medication. Prescribing moderate doses of agents from multiple classes can yield additive effects on blood pressure with less chance of increasing the risk of adverse events from high doses of individual drugs.

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

  • 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 a thiazide and a generic ACE inhibitor are especially useful.

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 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, take both compliance and cost into account.


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, and William H. Shrank, M.D., M.S.H.S., Instructor of Medicine, Harvard Medical School. Senior editor: Jerry Avorn, M.D., Professor of Medicine, Harvard Medical School. All are physicians at the Brigham and Women's Hospital in Boston. The Independent Drug Information Service (iDiS) is provided by the nonprofit ALOSA Foundation and is not affiliated in any way with any pharmaceutical company. These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient's clinical condition.


  1. Chobanian AV, et al.. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA; 2003;289:2560-72.
  2. 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:
  3. Law MR, et al.Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ;2003:1427-1434