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Hypertension Update: The Value of Combination Therapy

Issue: May 2010

By: Laybon Jones, M.D.

Despite all the advancements we have seen in the diagnosis and treatment of hypertension, this condition continues to be known as a silent killer. We see incidences all the time of strokes, heart attacks and kidney failure resulting from untreated hypertension; unfortunately, the patients did not notice—or perhaps ignored—any symptoms that would have led them to seek medical care.

Prevalence

All medical professionals, regardless of specialty, understand how critical it is to keep patients’ blood pressure within the “normal” 120/70 range. We can only have an effect on people who seek our counsel, and we cannot make those who are diagnosed change their lifestyles or take their medication, so the prevalence of hypertension in the U.S. remains far higher than any of us would like.

About one in every four American adults has high blood pressure; 25% of the population has hypertension that’s considered to be in the danger zone. Even more significantly, when you add in those who have pre-hypertension—a warning sign that they may suffer from high blood pressure in the future—that brings the number to almost 60 million, nearly half of our adult population.

What is particularly alarming is how many of these people are unaware of their condition. Figures from the 2003-2004 NHANES survey note that just 66.5% of those with hypertension are aware they have it. A little more than half (53.7%) of hypertensive patients are being treated but only 63.9% of them have their condition under control…meaning that just 33.1% of all hypertensives fall under the “controlled” category.

The Case for Treatment

Very few of the physical and fiscal costs that result from unchecked hypertension are unavoidable; the treatments available are not invasive or highly dangerous. It is our job to ensure that patients understand the risks they are exposing themselves to if they choose to ignore the potential for harm when hypertension is not treated.

Perhaps a list noting the complications that can arise from untreated high blood pressure would be helpful:

Atherosclerosis
Stroke
Heart disease
Kidney disease
Diabetes
Preeclampsia
Metabolic syndrome
Erectile dysfunction

We can also help raise awareness of symptoms that may occur when blood pressure is extremely high: severe headaches; fatigue or confusion; vision problems; chest pain; difficulty breathing; irregular heartbeat; blood in the urine; and pounding in the head, neck or ears. These can indicate a hypertensive crisis that could lead to a heart attack or stroke.

If all that falls on deaf ears, perhaps a more direct life-threatening message is required: for every 20/10 mmHg increase in blood pressure, the cardiovascular mortality risk doubles. The good news, however, is that even small reductions in blood pressure may result in large risk reductions for cardiovascular events; a 2 mmHg decrease in mean systolic blood pressure has been shown to result in a 7% reduction in risk of ischemic heart disease and a 10% reduction in risk of stroke mortality.

Treatment Advances

Over the past 70 years, the development of antihypertensive therapies has evolved from the use of peripheral sympatholytics, direct vasodilators, Thiazide diurectics and central a₂ agonists to calcium antagonists—DHPs, ARBs and direct renin inhibitors. ETa blockers and VPIs are also being investigated, but are not currently available for clinical use.

When lifestyle modifications like losing weight, getting more exercise, eating a healthier diet, and quitting smoking fail to bring patients to their goal blood pressure, we typically use a treatment algorithm that includes options for hypertension with and without compelling indications. For the former, stage 1 includes Thiazide-type diuretics for most patients, but we may also consider ACE inhibitors, ARB, ß-blocker, CCB or a combination; stage 2 consists of a two-drug combination that usually includes a Thiazide-type diuretic. For hypertension with compelling indications, we use drugs to treat those indications as well as other antihypertensive drugs (diuretics, ACE inhibitors, ARB, ß-blocker, and CCB) as needed.

In both instances, if the patient is still not at the goal pressure, we optimize dosages or add additional drugs until it is reached. One thing we have learned over the years is the need for multiple agents to control hypertension; monotherapy has been proven inadequate for about 40% to 50% of patients—most require two or more anti-hypertensives to reach their blood pressure goal.

We have also discovered that fixed-dose combination therapy results in improved adherence over free-combination therapy; the respective medication possession ratios are 88% and 69%.

Combination therapy has been used routinely in the past; fixed-dose combination therapy has become increasingly popular from a therapeutic and economic standpoint. Thiazide diuretics have been commonly added to almost any antihypertensive agent to provide an additional 5 to 15 mmHg lowering of blood pressure. ACE inhibitors in combination with a calcium channel blocker were actually first prescribed as fixed-dose drugs and are still in use. Various combinations now exist, including ARBs with calcium channel blockers, ARBs with diuretics, and direct renin inhibitors with either diuretics or ARBs. Most of these combinations provide blood pressure lowering in combination significantly beyond either of the individual components.

We must continue our vigilance to stop the vicious cycle of therapeutic failure associated with titrating doses of monotherapy. It is well documented that increased dosing to treat uncontrolled blood pressure can lead to an increased incidence of side effects, which may result in non-adherence to therapy…bringing us right back to uncontrolled blood pressure.

Laybon Jones, M.D. is a diagnostic and interventional cardiologist and the director of Cardiovascular Services at Sutter Solano Medical Center. He can be contacted through Solano Cardiovascular Consultants at 707-642-4155 or sccjones@yahoo.com.

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