Hypertension: Which Drugs for Which Patients?

An Expert Interview With Raymond R. Townsend, MD

Steven Fox

April 27, 2012

April 27, 2012 (New Orleans, Louisiana) — Editor's note: Strategies for managing hypertension have evolved significantly over the past decade. However, after numerous studies, clinicians still grapple with common issues, such as when to use single- vs multiple-drug therapy, how to treat hypertension in the elderly and very elderly, and how important ethnicity is in choosing antihypertensive drugs.

Those and other issues were the focus an educational program here at Internal Medicine 2012: American College of Physicians (ACP) Annual Meeting, held from April 19 to 21. It was presented by Raymond Townsend, MD, professor of medicine at the University of Pennsylvania, in Philadelphia.

To bring you highlights from that session, Medscape Medical News discussed it with Dr. Townsend via email.

Medscape: Which is better: a higher dose of a single antihypertensive drug or multiple drugs at less than maximal doses?

Dr. Townsend: Many drugs have the majority of their antihypertensive effect at about half maximal dose. Increasing the dose may reduce blood pressure a few more mm Hg, but at the risk of substantial increases in the side-effect profile. Usually, the most prudent course is to add an agent rather than to press on to maximal dosage.

Medscape: How does race figure into your choice of drugs for the management hypertension?

Dr. Townsend: It is a bigger factor with monotherapy than with combination drug therapy. Once you get to 2 or more drugs, racial responses tend to blend together. Fewer than half of the people with hypertension are controlled with a single agent, so it is more often an issue of control, rather than which drug first. The hard part is getting past the "milestone" of needing more than 1 drug.

Medscape: Can you summarize the high points of current guidelines for antihypertensive drugs?

Dr. Townsend: Efficacy, safety/tolerability, and cost — in that order. Any agent that's on the market has been through a reasonably rigorous approval process, so it is clear they all work, and blood pressure reduction is assumed.

Established benefit is the current fashion in initiating treatment. Most classes have large trials establishing their benefit. In the past, it was an issue of drug treatment vs placebo. But now, with established benefit, drug treatment is a given.

Within the classes of antihypertensive medication, virtually all are reasonable choices for young to middle-aged otherwise uncomplicated hypertensives. In older patients, the beta-blocker class has become less popular, principally based on studies conducted in the late 1990s and early 2000s, which showed less benefit with beta blockade (most commonly atenolol) than with most other drug classes, particularly for stroke protection. The "compelling" indications for certain drugs, like ACE inhibitors in high cardiovascular-risk patients and angiotensin-receptor blockers (ARBs) in type 2 diabetes patients with proteinuria, continue to make sense.

Medscape: When managing patients with hypertension, is there a particular drug sequence you favor in initiating treatment?

Dr. Townsend: It depends in part on the starting blood pressure. If you begin with fairly high pressure, especially a systolic greater than 160 mm Hg or a diastolic greater than 100 mm Hg, it makes sense to start a 2-drug combination; it will achieve control more quickly and require fewer in-office visits for titration.

Sensibly combining drugs requires appreciating the primary mode of action in the various classes of drugs. The goal in combining classes is to leverage different mechanisms of action and, when possible, to offset a known side-effect profile. For example, the use of ACE inhibitors with diuretics leverages 2 distinct mechanisms of blood pressure increase; at the same time, the ACE inhibitor tends to blunt the potassium losses associated with the diuretic.

Medscape: Are there optimal combinations of antihypertensives, or combinations that have proven effective in particular subpopulations of patients?

Dr. Townsend: The evidence here is meager and limited to 3 large studies. In ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), therapy with an ACE inhibitor plus calcium-channel blocker had better cardiovascular outcomes than a beta blocker plus diuretic, despite similar reductions in blood pressure. In the ACCOMPLISH (Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension) trial, an ACE inhibitor plus calcium-channel blocker had better cardiovascular outcomes than an ACE inhibitor plus diuretic. In ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial), there was no improvement in outcomes with the combination of an ACE inhibitor plus ARB, compared with an ACE inhibitor or an ARB alone, despite a few mm Hg of additional lowering of blood pressure. More combination drug-therapy trials would be welcome.

Medscape: What points do clinicians need to keep in mind when managing elderly and very elderly patients?

Dr. Townsend: Mainly 2 things. Polypharmacy — where they may be taking many other agents for a variety of comorbidities — can often lead to drug interactions, so it's important to watch for those sorts of situations. Another point to be mindful of is the loss of some baroreceptor function that occurs with aging. When coupled with some drugs, that can predispose older patients to orthostasis and injury from falls.

Medscape: Are there any new classes of antihypertensives or individual drugs in the pipeline that might be available in the next few years?

Dr. Townsend: There are agents in development that block rho-kinase with some vascular effects, and some that combine ARBs with neutral endopeptidase inhibition. Those are 2 of the main areas to keep an eye on.

Dr. Townsend reports serving as a consultant to Medtronic, Concert Pharmaceuticals, and Merck; receiving grant support from the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases.