Systolic and diastolic blood pressure control in antihypertensive drug trials

All published studies agree that hypertension is a poorly diagnosed and treated condition 1,2. That is, (i) in all countries, the number of subjects in which hypertension is identified is noticeably smaller than that suffering from a blood pressure elevation; (ii) individuals who, after the diagnosis of hypertension, undergo antihypertensive treatment are even less; and (iii) those who have their blood pressure reduced below 140/90 mmHg (systolic/diastolic) because of treatment are no more than a minimal fraction of the overall or even the treated hypertensive population. Indeed, the world situation is even worse than it appears from these data because adequate antihypertensive treatment is poorly implemented even in patients with diabetes 3, nephropathy 4 or prior myocardial infarction 5,6, in whom blood pressure reductions have extremely large life- or disease-saving effects. Furthermore, control rate is particularly low for systolic blood pressure 7,8, which prevails over the diastolic counterpart in determining the overall risk profile 9,10. Finally, the number of patients with controlled blood pressures becomes dramatically small if values well below 140/90 mmHg (i.e. those offering the greatest degree of protection in several conditions) are considered. Two main explanations have received large credit for the frequent lack of blood pressure control in the treated hypertensive population. One explanation is that, for a variety of reasons, patient compliance to treatment is low 11. The other is that physicians contribute to this phenomenon in several ways: failure to properly inform and motivate patients; inability to see them as often as needed; and insistance on moving from one monotherapy to another when the antihypertensive response is inadequate without resorting to combination of two or more drugs, thus envisaging a multimechanicistic approach to a multifactorially governed variable such as blood pressure 12. The above explanations imply that when patient compliance and the expertise of physicians are adequate, blood pressure can be effectively lowered to goal levels. This may be the case for diastolic but not for systolic values, however. Figure 1 shows the blood pressure values in several recent controlled trials on antihypertensive individuals 13–22, that is under conditions in which patient motivation and adherence to treatment on one side, and the ability of physicians to use appropriate drug combinations and doses on the other, unquestionably met high standards. It can be seen that whenever the initial blood pressures were high, treatment was accompanied by large blood pressure reductions. However, while the achieved average diastolic blood pressure was almost invariably well below 90 mmHg and even 80 mmHg, the concomitant systolic value remained above or only slightly below 140 mmHg, the number of individual patients with ‘on treatment’ values below 90 and 140 mmHg being approximately 90 and 50%, respectively 13–22. This is also the case in diabetic hypertensive patients (Fig. 2) in whom the achieved blood pressure values were higher than in non-diabetic patients despite the use of a larger number of drugs (Fig. 3) 23–34. Thus, the conclusion can be drawn that even when patient compliance and physicians’ expertise are ensured, systolic blood pressure control is neither frequently nor easily obtained. Furthermore, this goal requires drug doses and combinations that go far beyond those necessary for diastolic blood pressure control. This should be kept in mind when recommendations to lower systolic blood pressure to values well below 140 mmHg, or even 130 mmHg, are given to general practitioners as if they were realistic values to obtain in their patients 1,2.Fig. 1: Effects of antihypertensive drug treatment on systolic (S) and diastolic (D) blood pressure (BP) in trials on essential hypertensive patients. Blood pressure values at trial entry (B) and values achieved during treatment (T) are shown for each trial. Dashed horizontal lines refer to goal blood pressure values indicated by International Guidelines to be achieved during treatment. Based on previously published data 13–22.Fig. 2: Effects of antihypertensive drug treatment on systolic (S) and diastolic (D) blood pressure (BP) in diabetic hypertensive patients of several trials. Values at trial entry and during treatment are shown for each trial. Dashed horizontal lines refer to goal blood pressure values indicated by International Guidelines to be achieved during treatment. Based on previously published data 23–32.Fig. 3: Systolic (S) and diastolic (D) blood pressure (BP) values achieved during treatment in three trials performed in diabetic hypertensives. Data are shown as mean values. The number of drugs employed in these patients are reported at the bottom. Based on previously published data 14,15,31.We see three possibilities ahead: (i) to accept that optimal systolic blood pressure control will never be frequently achievable, possibly because systolic blood pressure elevation is due in part to large artery wall thickening and this may not be entirely reversible. (ii) To count on the availability of new drugs with a more powerful effect on systolic blood pressure. (iii) To advise the systematic use of multiple combinations of drugs given at full doses (i.e. an approach which has been found to increase the rate of systolic blood pressure control in the VALUE Study) 35. However, it should be noted that in this study the percentage of treated hypertensive patients without systolic blood pressure control still remained elevated, approaching the rate of the concomitant diastolic blood pressure control (Julius S., personal communication).