Hypertension Treatment: Contributions and Comments on Challenges

I believe my major contribution was the Veterans Administration (VA) Cooperative Study on the prevention of morbid events using antihypertensive drug treatment. The principal conclusions of this trial were as follows:

• •The study proved for the first time in patients with moderately severe to severe hypertension that morbidity and mortality were significantly reduced by lowering blood pressure with antihypertensive drug treatment.
• •This demonstration reversed much of the medical opinion at that time, which stated that no attempt should be made to reduce blood pressure with medications in patients with essential hypertension.
• •The VA study was also the first example of a multiclinic, prospective, randomized, double‐blind trial for determining the effectiveness of treatment in cardiovascular diseases. It established a model for future trials.
• •Hypertension is the most common cause of death in the United States and other developed countries. Our VA study, therefore, has had a considerable impact on medical treatment both here and in the rest of the world.

Other contributions to the treatment of hypertension of which I am a part include the first official announcement (at the annual meeting of the American Heart Association in fall 1957) of the antihypertensive effectiveness of the thiazide diuretics when used alone and in enhancing the antihypertensive effectiveness of other blood pressure‐lowering drugs. The observation led me to use combination treatment with a thiazide plus other drugs as initial treatment, a method we started using in the VA trial 35 years ago and have used since.

Dr. Moser and I have consistently defended the thiazide diuretics against ill‐founded claims of their toxicity. We have come a long way since we first compared notes in 1952 on the use of adrenergic blockade for lowering blood pressure. I believe small, fixed‐dose combination drugs containing a diuretic as one of the constituents will one day replace monotherapy as the most effective way to initiate antihypertensive drug treatment.

NOTES ON COMPLIANCE

At present, compliance is probably the most important challenge in the treatment of hypertension. What can a physician do about it? Here are some suggestions from an old‐timer that you may find useful:

• •Reduce the blood pressure as rapidly as can be done safely. This impresses the patient with the seriousness of the disorder and with the skill of the doctor.
• •Adjust drugs and doses rapidly by making weekly, rather than monthly, appointments during the drug titration period. Set your treatment goal to have the patient reach the blood pressure goal in fewer than 30 days. The patient should be impressed that you consider the disorder serious and urgent.
• •Two or more drugs are usually needed to lower blood pressure to <140/90 mm Hg (in diabetics and patients with renal disease to <130/80 mm Hg).
• •Initiate treatment with the smallest available dose of a two‐drug combination tablet. Titrate up to the next higher‐strength combination tablet as needed.
• •Combination drugs are less likely to produce side effects than monotherapy because the dose of each component is less than the dose required to reduce the blood pressure to the same degree using one drug. Side effects are dose related.
• •It is well established that compliance is improved if the patient is required to take one tablet once daily rather than several tablets more than once per day.
• •Use fixed‐dose combination drugs that contain a diuretic, such as 12.5–25 mg chlorthalidone. In a controlled trial, Materson et al. ¹ demonstrated that combination drugs containing a diuretic as one of the constituents reduced systolic blood pressure to 140 mm Hg in 77% of patients, significantly more than the average of 49% of patients who had their blood pressure reduced by treatment with combinations not containing a diuretic.
• •A compassionate and motivated nurse may do a better job at follow‐up care and obtain better long‐term compliance than most doctors. Nurses can spend more time with a patient, emphasizing the importance of continuous control of blood pressure and answering questions.
• •Home blood pressure measurements taken by a family member or the patient him‐ or herself makes the patient a partner in achieving goal pressure.

Many patients, including some who are well educated, have a fear of taking "chemicals" for the rest of their lives. This fear is fostered by exaggerated and often erroneous media claims of death or disability caused by some well known drug. I ask my patients if they have this fear. If they do, I tell them the drugs I am prescribing for them have been used in millions of people for at least 10 years. It is extremely doubtful that a serious toxic effect would not have been recognized within that time. However, because almost all drugs have some side effects, patients should be told what they are so they can be recognized and changes can be made as indicated.

Some of you may be curious if I take antihypertensive drugs. I do, and at age 91 years, my blood pressure is maintained between 110/60 mm Hg and 125/70 mm Hg. I have never felt weak or faint at these levels.