Guidelines and Goals in the Management of Hypertension
Guidelines and Goals in the Management of Hypertension
Do the official hypertension guidelines make sense, and does it really matter whether physicians promote their compliance?
National and international recommendations for the treatment of hypertension have universally included a goal of < 140/90 mm Hg for the majority of hypertensive patients. These guidelines have been formulated to apply to both young and old patients, even those above the age of 75 or 80 years with isolated systolic hypertension (ISH). The guidelines also apply to those with some target organ involvement, although recently these have been changed to recommend levels of < 130/80 mm Hg for patients with diabetes or evidence of proteinuria and renal disease.
In the elderly: The 140/90 mm Hg goal is an easy one to justify. Although cardiovascular risk increases linearly with increases in systolic blood pressure (SBP) above 110 mm Hg, a more rapid increase in risk is noted when blood pressure exceeds 140/90 mm Hg. It has been demonstrated in numerous clinical trials that reducing elevated blood pressures to below these artificial cutpoints has benefits for risk reduction, but whereas it has been possible to reduce diastolic blood pressure (DBP) to < 90 mm Hg in most studies, it has proven more difficult to achieve SBP < 140 mm Hg, especially in older patients.
Thus, while results from clinical trials suggest that elderly patients tolerate blood pressure lowering without too much difficulty and that these fairly rigorous goal blood pressures are attainable, in several recent clinical trials enrolling elderly patients, SBP levels < 140 mm Hg were not achieved in a great many subjects.
For example, in the Systolic Hypertension in the Elderly Program (SHEP) trial, initial SBP levels were 170 mm Hg in both placebo and treated groups. Goal SBP levels had been set at < 160 mm Hg for those who started at pressures > 180 mm Hg, and a reduction of 20 mm Hg for those who started at pressures of 160-179 mm Hg. However, even with these more modest criteria, only 65% to 72% of patients in the treated group achieved goal pressures, although mean SBP levels in the diuretic-based treated group reached 143 mm Hg by the end of the trial. DBP levels were 77 mm Hg at the beginning of the trial and 68 mm Hg at 5 years in the treated group, vs 76 and 71 mm Hg, respectively, in the placebo group -- a difference of only -1/-3 mm Hg DBP between the 2 groups at trial beginning and end.
In the Systolic Hypertension in the Elderly trial in Europe (Syst-Eur), mean baseline pressures were 174/86 mm Hg in the treated and control groups. At 2 years, these had been reduced to 151/79 mm Hg in the treated group and 160/83 mm Hg in the placebo group, but goal blood pressures were achieved in only 43% of the treated patients.
In both of these trials with elderly patients, the problem was ISH; the mean DBP was not elevated prior to therapy. Yet despite this failure to achieve SBP goals, a statistically significant reduction in cardiac events was noted in both of these trials. Therefore, one of the important implications of these trials is that recommendations for the elderly should state that, although it is desirable to achieve goal pressures of < 140/90 mm Hg, a reduction in cardiovascular events will be noted with decreases in blood pressure to levels close to, although not quite at or below, recommended goals; furthermore, if goal pressures are attained, benefits may be even greater than those seen in clinical studies.
In renal disease: Retrospective analysis of the Modification of Diet in Renal Disease (MDRD) trial indicated less progression of renal disease in those patients with blood pressure levels < 125/75 mm Hg. The African American Study of Kidney Disease and Hypertension (AASK) results also suggested that the lower the blood pressure in patients with renal disease, the better the outcome.
In diabetes: In the United Kingdom Prospective Diabetes Study (UKPDS), more than 1100 diabetic patients were treated with different antihypertensive regimens. Those patients who achieved tight blood pressure control (144/82 mm Hg) compared with those who achieved less tight blood pressure control (154/87 mm Hg), a difference of only -10/-5, achieved a marked decrease in both diabetic and nondiabetic cardiovascular complications. This study indicates that careful blood pressure control, especially in diabetic patients, is beneficial. Since the mean tight blood pressure control result was 144/82 mm Hg, it is obvious that many of the patients in this group must have achieved blood pressures considerably lower than 140/80 mm Hg. A subset analysis of the patients who achieved SBP levels < 140 mm Hg indicates additional benefit as pressure was lowered. Thus, an SBP goal of < 130 mm Hg in diabetic persons appears to be a reasonable one, if it can be achieved.
The Hypertension Optimum Treatment (HOT) study in Sweden attempted to answer the question, Is there a difference in outcome if blood pressure levels are lowered more in one group than in another? In other words, does it matter how blood pressure is lowered -- ie, which drug regimen is used?
In this trial, there were no statistically significant differences between patients who achieved an average DBP of 85 mm Hg and those who achieved 83 or 81 mm Hg, except in patients with diabetes, where a difference of only 4 mm Hg (achieved DBP levels of 85 and 81 mm Hg, respectively) made a statistically significant difference in outcome. In short: Lower is better, regardless of how it is achieved. (This was one of the studies that led to recommendations that diabetic patients should have their DBP levels lowered to < 85 mm Hg.)
Many investigators believe that goal blood pressure should be set even lower -- as close to 120/80 mm Hg as possible -- and that therapy should be continued until these levels are achieved or until side effects are noted or there is some interference with the quality of life. "Quality of life" may be one of the limiting factors in achieving goal blood pressures in elderly patients with ISH. For example, it is often noted that as SBP decreases from 180 to 160 or 150 mm Hg in an elderly patient, he or she feels tired or is unwilling to increase medication further. Even though goal blood pressures have not been achieved, it is often prudent to maintain the pressure at this new level and wait until there is some baroreceptor adjustment. In several months, a change in medication can be tried.
The recently completed Major Results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the largest clinical hypertension trial ever conducted, suggests that blood pressure can be reduced to levels close to recommended goals in a high percentage of patients. Mean age in this trial was 67 years of age, indicating a relatively older population, and yet, with a total enrollment of > 33,000 patients, > 90% achieved DBP goals of < 90 mm Hg; 60% achieved SBP goals of < 140; and 66% achieved blood pressure levels < 140/90 mm Hg. These results were achieved in an ethnically diverse enrollment, in a widely dispersed North American region, and in private practice or public clinic settings. An important caveat to these results is that > 60% of the patients required ≥ 2 medications for control. Nevertheless, in a private-practice follow-up study of more than 8 years' duration, almost 80% of patients achieved the stringently defined goal blood pressure levels, even though the choice of medications was limited by trial design at the time of the study.
Some physicians object to rigid guidelines regarding target blood pressure goals. No one can object, however, to the concept of reducing blood pressure to as close to 120/80 mm Hg as possible if this can be done without interfering with the enjoyment of life. The important lesson to be drawn from the recent clinical trial results is that there are effective and safe medications -- especially if they are employed in the appropriate combinations -- that are capable of accomplishing these lower goal levels. It is incumbent upon all physicians to utilize these agents in appropriate dosages and appropriate combinations so that a greater reduction in cardiovascular events can be achieved. Another important message: There is little evidence to support the notion that reducing blood pressure to even lower levels than those set in recent recommendations poses any danger.
Do the official hypertension guidelines make sense, and does it really matter whether physicians promote their compliance?
National and international recommendations for the treatment of hypertension have universally included a goal of < 140/90 mm Hg for the majority of hypertensive patients. These guidelines have been formulated to apply to both young and old patients, even those above the age of 75 or 80 years with isolated systolic hypertension (ISH). The guidelines also apply to those with some target organ involvement, although recently these have been changed to recommend levels of < 130/80 mm Hg for patients with diabetes or evidence of proteinuria and renal disease.
In the elderly: The 140/90 mm Hg goal is an easy one to justify. Although cardiovascular risk increases linearly with increases in systolic blood pressure (SBP) above 110 mm Hg, a more rapid increase in risk is noted when blood pressure exceeds 140/90 mm Hg. It has been demonstrated in numerous clinical trials that reducing elevated blood pressures to below these artificial cutpoints has benefits for risk reduction, but whereas it has been possible to reduce diastolic blood pressure (DBP) to < 90 mm Hg in most studies, it has proven more difficult to achieve SBP < 140 mm Hg, especially in older patients.
Thus, while results from clinical trials suggest that elderly patients tolerate blood pressure lowering without too much difficulty and that these fairly rigorous goal blood pressures are attainable, in several recent clinical trials enrolling elderly patients, SBP levels < 140 mm Hg were not achieved in a great many subjects.
For example, in the Systolic Hypertension in the Elderly Program (SHEP) trial, initial SBP levels were 170 mm Hg in both placebo and treated groups. Goal SBP levels had been set at < 160 mm Hg for those who started at pressures > 180 mm Hg, and a reduction of 20 mm Hg for those who started at pressures of 160-179 mm Hg. However, even with these more modest criteria, only 65% to 72% of patients in the treated group achieved goal pressures, although mean SBP levels in the diuretic-based treated group reached 143 mm Hg by the end of the trial. DBP levels were 77 mm Hg at the beginning of the trial and 68 mm Hg at 5 years in the treated group, vs 76 and 71 mm Hg, respectively, in the placebo group -- a difference of only -1/-3 mm Hg DBP between the 2 groups at trial beginning and end.
In the Systolic Hypertension in the Elderly trial in Europe (Syst-Eur), mean baseline pressures were 174/86 mm Hg in the treated and control groups. At 2 years, these had been reduced to 151/79 mm Hg in the treated group and 160/83 mm Hg in the placebo group, but goal blood pressures were achieved in only 43% of the treated patients.
In both of these trials with elderly patients, the problem was ISH; the mean DBP was not elevated prior to therapy. Yet despite this failure to achieve SBP goals, a statistically significant reduction in cardiac events was noted in both of these trials. Therefore, one of the important implications of these trials is that recommendations for the elderly should state that, although it is desirable to achieve goal pressures of < 140/90 mm Hg, a reduction in cardiovascular events will be noted with decreases in blood pressure to levels close to, although not quite at or below, recommended goals; furthermore, if goal pressures are attained, benefits may be even greater than those seen in clinical studies.
In renal disease: Retrospective analysis of the Modification of Diet in Renal Disease (MDRD) trial indicated less progression of renal disease in those patients with blood pressure levels < 125/75 mm Hg. The African American Study of Kidney Disease and Hypertension (AASK) results also suggested that the lower the blood pressure in patients with renal disease, the better the outcome.
In diabetes: In the United Kingdom Prospective Diabetes Study (UKPDS), more than 1100 diabetic patients were treated with different antihypertensive regimens. Those patients who achieved tight blood pressure control (144/82 mm Hg) compared with those who achieved less tight blood pressure control (154/87 mm Hg), a difference of only -10/-5, achieved a marked decrease in both diabetic and nondiabetic cardiovascular complications. This study indicates that careful blood pressure control, especially in diabetic patients, is beneficial. Since the mean tight blood pressure control result was 144/82 mm Hg, it is obvious that many of the patients in this group must have achieved blood pressures considerably lower than 140/80 mm Hg. A subset analysis of the patients who achieved SBP levels < 140 mm Hg indicates additional benefit as pressure was lowered. Thus, an SBP goal of < 130 mm Hg in diabetic persons appears to be a reasonable one, if it can be achieved.
The Hypertension Optimum Treatment (HOT) study in Sweden attempted to answer the question, Is there a difference in outcome if blood pressure levels are lowered more in one group than in another? In other words, does it matter how blood pressure is lowered -- ie, which drug regimen is used?
In this trial, there were no statistically significant differences between patients who achieved an average DBP of 85 mm Hg and those who achieved 83 or 81 mm Hg, except in patients with diabetes, where a difference of only 4 mm Hg (achieved DBP levels of 85 and 81 mm Hg, respectively) made a statistically significant difference in outcome. In short: Lower is better, regardless of how it is achieved. (This was one of the studies that led to recommendations that diabetic patients should have their DBP levels lowered to < 85 mm Hg.)
Many investigators believe that goal blood pressure should be set even lower -- as close to 120/80 mm Hg as possible -- and that therapy should be continued until these levels are achieved or until side effects are noted or there is some interference with the quality of life. "Quality of life" may be one of the limiting factors in achieving goal blood pressures in elderly patients with ISH. For example, it is often noted that as SBP decreases from 180 to 160 or 150 mm Hg in an elderly patient, he or she feels tired or is unwilling to increase medication further. Even though goal blood pressures have not been achieved, it is often prudent to maintain the pressure at this new level and wait until there is some baroreceptor adjustment. In several months, a change in medication can be tried.
The recently completed Major Results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the largest clinical hypertension trial ever conducted, suggests that blood pressure can be reduced to levels close to recommended goals in a high percentage of patients. Mean age in this trial was 67 years of age, indicating a relatively older population, and yet, with a total enrollment of > 33,000 patients, > 90% achieved DBP goals of < 90 mm Hg; 60% achieved SBP goals of < 140; and 66% achieved blood pressure levels < 140/90 mm Hg. These results were achieved in an ethnically diverse enrollment, in a widely dispersed North American region, and in private practice or public clinic settings. An important caveat to these results is that > 60% of the patients required ≥ 2 medications for control. Nevertheless, in a private-practice follow-up study of more than 8 years' duration, almost 80% of patients achieved the stringently defined goal blood pressure levels, even though the choice of medications was limited by trial design at the time of the study.
Some physicians object to rigid guidelines regarding target blood pressure goals. No one can object, however, to the concept of reducing blood pressure to as close to 120/80 mm Hg as possible if this can be done without interfering with the enjoyment of life. The important lesson to be drawn from the recent clinical trial results is that there are effective and safe medications -- especially if they are employed in the appropriate combinations -- that are capable of accomplishing these lower goal levels. It is incumbent upon all physicians to utilize these agents in appropriate dosages and appropriate combinations so that a greater reduction in cardiovascular events can be achieved. Another important message: There is little evidence to support the notion that reducing blood pressure to even lower levels than those set in recent recommendations poses any danger.
