New insights in managing hypertension

High blood pressure (BP) remains as a leading cardiovascular problem leading to strokes and heart attacks, and despite advances in its treatment, there is still much to be desired to prevent its dreaded complications.

Newer forms of therapy, however, have emerged which can confer benefits on the hypertensive patients beyond lowering of the BP. This has put a new standard on antihypertensive therapy that it must not only lower BP, but preferably have an antiatherosclerotic effect as well, so as to reduce the incidence of life-threatening complications of elevated blood pressure.

Recent data strongly suggest an antiatherosclerotic effect of the calcium antagonist lacidipine independent of its antihypertensive effect. Atherosclerosis is the progressive narrowing of the blood vessels leading to impaired perfusion of the organs and ultimately causing heart attacks and strokes.

This beneficial antiatherosclerotic effect of lacidipine was the conclusion of the European Lacidipine Study on Atherosclerosis (ELSA), which was presented by Professor Alberto Zanchetti, MD, during a dinner symposium held at the EDSA Shangri-La Hotel recently.

ELSA, done in seven European countries, is the largest well-designed trial on atherosclerosis in hypertension using carotid wall intima-media thickness (IMT) as the primary parameter. Lacidipine was compared to the beta-blocker atenolol in the trial. The carotid arteries supply the brain and when there is carotid atherosclerosis, the chances of having coronary atherosclerosis (involving the heart) is also high.

According to Zanchetti, head of the Hypertension Section at the University of Milan, previous trials of antihypertensive treatment assessing the incidence of cardiovascular events do not provide information on progression or regression of underlying blood-vessel disease, in particular atherosclerosis. The mechanisms responsible for precipitating events are often different from mechanisms responsible for the development of vascular disease.

Zanchetti noted that there was a trend toward less strokes and cardiovascular deaths in lacidipine-treated patients. The greater efficacy of lacidipine on the progression and regression of atherosclerotic plaques despite similar blood pressure effects, supports a greater efficacy of lacidipine over atenolol on atherosclerosis progression in hypertensive patients, and that this antiatherosclerotic effect is independent of the antihypertensive effect.

Combination therapy

In another lecture in the same symposium, Dr. Rody Sy, president of the Asia-Pacific Society of Atherosclerosis and Vascular Diseases (APSAVD), discussed the role of combination therapy in meeting blood pressure targets.

Data from the landmark United Kingdom Prospective Diabetes Study showed that three or more antihypertensive agents are needed for patients who need tight BP control. Conventional strategies based on single therapy will likely need modification to achieve ideal BP levels in the greater number of patients.

According to Sy, combination therapy yields greater antihypertensive efficacy due to complimentary mechanisms of action, which results in higher patient response rates. It facilitates ease of administration as it simplifies titration and dosing schedules. It also results in an improvement of the patient’s adherence to therapy due to once-daily dosing.

One combination, which proved to be effective in meeting aggressive BP target, is the combination of angiotensin receptive blocker (ARB) and diuretic hydrochlorothiazide (HCTZ). When combined, ARB and HCTZ enhance BP control through a balance of drug effects. Diuretics reduce fluid volume, while ARBs decrease blood-vessel resistance.

Sy cited a well-designed study evaluating the combination of telmisartan ARB, with HCTZ. "Telmisartan with the low-dose diuretic provides added efficacy while reducing the risk of metabolic disturbances," he said.

He reported that there is a greater reduction in the BP with the combination of 40 mg telmisartan and 12.5 mg HCTZ compared to either the 40 mg telmisartan or 12.5 mg HCTZ alone.

The same thing is true with the combination of 80 mg telmisartan and 12.5 mg HCTZ. This was more significant compared to the monotherapy of either drug, Sy added.

With regards to the drop in potassium, a blood element which is usually affected by diuretic therapy, Sy noted that there was hardly a difference shown in the original potassium level of the patients taking the combination of 80 mg telmisartan and HCTZ.

The study further concluded that the combination of telmisartan and HCTZ is well-tolerated, and is associated with a low incidence of adverse events during clinical trials. Adverse events were transient and mild with a low incidence of cough.

More importantly, the study showed that telmisartan combined with HCTZ maintains a clinically significant long-term therapeutic effect.

The advent of the telmisartan and HCTZ combination offers physicians another treatment option for patients who are unable to control their hypertension with a single agent. This could mean great hope for people with elevated blood pressure.