THE UTILITY FUNCTION OF ANTIHYPERTENSIVE THERAPY: DISCUSSION

Discussant: Alvin P. Shapiro

University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania 15261

As a clinical pharmacologist myself, I can only admire what Dr. Melmon has tried to do, namely to provide us with a mechanism to obtain objective data on treatment and its problems. He has indicated that we need data on the probabilities of both harm and benefit from the drugs and that we also need data on the patient’s perception of his treatment. The more we make asympto- matic people symptomatic, the more we have to recognize the patient’s right to a choice, and we have to pose this choice clearly for him.

Although we talk a lot about epidemiology, we frequently wonder how epidemiologic data apply to the individual patient. I do not generally believe in anecdotal teaching, but sometimes it is helpful to examine what happens to individual patients. The first case demonstrates one of my “personal triumphs” in achieving Dr. Moses’ goal of “converting the asymptomatic to the sympto- matic.” A 50-year-old man with a rather high blood pressure on no treatment came to me with no symptoms. He was given alpha-methyldopa and developed the fever and liver changes that sometimes accompany this drug. His treatment was changed to thiazide and reserpine, but his uric acid rose and gout ensued. This was countered with allopurinol; his uric acid came down, but he quickly developed a severe generalized rash. With no therapy, his blood pressure climbed back up, and he was started on guanethidine, which left him asympto- matic but only partially controlled. Several weeks later he developed diarrhea from this agent, and at that point he stopped seeing me until he came back a year later in heart failure. Subsequently he did relatively well on digitalis and spironolactone; he felt well but developed gynecomastia. This is, of course, a single case report, but a discouraging one, illustrating side effects from five drugs in one patient.

The dilemmas we face in treating the individual hypertensive patient include the variability of blood pressure, the variability of drug responses, the patho- pharmacology of drugs, and renal impairment if the blood pressure falls too low. However, even in very severe hypertensives, the latter is much less of a problem today than it used to be because of the availability of renal dialysis. Finally, there is the variability of prognosis in the individual patient. We have all seen the occasional 75-year-old woman who has had blood pressures of 220/ 120 mm Hg for 30 years without complications.

My second anecdote is about a somewhat more successful case and involves a lady who was 27 in 1957 at which time she had malignant hypertension (Grade IV fundi) with heart failure but fortunately with good renal function. I am still following her 20 years later. During this time, her diastolic pressure in the re- clining position was never well controlled ( 1 10-1 30 mm Hg) ; upright, however, it was better controlled (90-120) mm Hg). She has received virtually every drug developed during that 20 years. She was on mecamylamine and developed paralytic ileus, which led to mechanical obstruction and required surgery. She

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was on alpha-methyldopa and became so drowsy we had to stop it. She was on guanethidine and thiazide for a good many years but eventually developed gout. On spironolactone, she continued to have attacks of gout until allopurinal was instituted. Then, while still on guanethidine and digitalis, she developed A-V block and an arrhythmia. A brief trial of minoxidil resulted in severe hirsutism. Now she is doing reasonably well on spironolactone and propranolol, with continued digitalis. In spite of all of these iatrogenic events, she has functioned well over these many years without clinical heart failure and with only a slight rise in creatinine (1.0 to 1.7 mg 5%). Thus, she is a “therapeutic triumph” without having her blood pressure controlled. Of course, the pressure recorded in clinic may not represent her usual pressure, emphasizing that we will never know the actual level of blood pressure and its relationship to therapy and to progression of the disease until we can monitor continuously and determine the entire area under the 24-hour blood pressure curve.

Finally, the risk of “premature death” in the hypertensive is considered to be two times normal. If, however, we look at actual years of life expectancy, a 45-year-old man with a diastolic blood pressure below 90 mm Hg has a life expectancy of 31 years which gets him to 76. If his pressure is 90 mm Hg, he has only half the chance of reaching that life expectancy of 76 years; however, he will live some 28 years on the average, bringing him to 73. The man with a diastolic pressure of 100 mm Hg will on the average live 21 years to 66, rather than to 76. Looked at in this way, the patient has a choice, and he has time before he must start therapy. I, myself, of course, have become a “treater.” I use drugs all the time, and I have been involved in evaluating almost every drug that has come “down the pike” in the last 25 years. Nonetheless, I worry about the potentially negative effects of long-term drug therapy in mild hyper- tensives. Patients should know more about the things that worry me so that they can make value-judgments, particularly as we treat milder and earlier stages of the disease. The value-judgment is similar to that which I must make as a smoker. Since I am constantly abused by my friends and acquaintances because I continue to smoke, I have developed a not entirely facetious come- back; I tell them that my choice for reducing risk factors is wearing my seatbelts. This philosophy may be pertinent to the dilemmas we are discussing today.