Author + information
- Alan H. Gradman, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Alan H. Gradman, 1239 Shady Avenue, Pittsburgh, Pennsylvania 15232.
For the past several years, many physicians have been puzzled by the rapidly changing recommendations for the treatment of hypertension. The belief that “lower is better” has been challenged, and emphasis has been placed upon the risks accompanying excessive blood pressure (BP) reduction. In most recent guideline revisions, higher thresholds for initiating treatment and less aggressive BP targets have been adopted for patients with diabetes or chronic kidney disease (CKD) and the elderly (1). These decisions were prompted by meta-analyses of clinical trials, retrospective studies relating on-treatment BP to clinical outcomes, and ACCORD (Action to Control Cardiovascular Risk in Diabetes), a prospective trial in diabetic patients in which treatment to a systolic blood pressure (SBP) target of <120 mm Hg was not found to be superior to a higher target of <140 mm Hg (2,3).
With the publication of the SPRINT (Systolic Blood Pressure Intervention Trial), the tide has reversed (4). SPRINT was the largest trial ever conducted that was specifically designed to evaluate BP targets. In SPRINT, 9,361 subjects who were >50 years of age, had SBP >130 mm Hg, and had evidence of high cardiovascular (CV) risk were randomized to target BPs of <140 or <120 mm Hg. The choice of drugs for individual patients was not specified. Patients assigned to the lower SBP target exhibited a 25% reduction in the primary composite endpoint of major CV events and 23% lower mortality compared with those randomized to an SBP <140 mm Hg.
In this issue of the Journal, Bress et al. (5) explore the practical implications of SPRINT. They extrapolated findings from 17,085 participants in the National Health and Nutrition Examination Survey to the U.S. population to estimate the number of individuals whose treatment would be altered if the SPRINT results were implemented. Of the 16.8 million people who meet the SPRINT inclusion criteria, antihypertensive therapy would be initiated or intensified in 6.6 million with SBP 130 to 139 mm Hg. Additionally, the authors project that 25.5 million U.S. persons age >50 years with SBP >120 mm Hg are at increased CV risk. They speculate that if a BP target <120 mm Hg is accepted as the treatment standard, these individuals might also be candidates for treatment.
The results of SPRINT imply that the threshold for treatment should be reduced to 130 mm Hg and target SBP to <120 mm Hg in a large segment of the population, including 35% of patients with treated hypertension and 19% of untreated patients with BP 130 to 139 mm Hg. The latter group consists of patients with CKD (estimated glomerular filtration rate 20 to 60 ml/min/1.73 m2), coronary artery disease (CAD), a 10-year risk of CV disease >15% as estimated by the Framingham Risk Score, and all individuals >75 years of age with SBP >130 mm Hg. Patients with diabetes are not affected as they were not studied in SPRINT.
A key clinical question relates to management of treated hypertensive patients with SBP 130 to 139 mm Hg. Is it necessary to prescribe additional medication to further reduce BP? Certainly, the results of SPRINT do not apply to patients with resistant hypertension, usually defined as the need for >3 antihypertensive agents including a diuretic. Drug-resistant patients were excluded from SPRINT by a screening algorithm that set an upper SBP limit for each patient on the basis of the number of drugs taken at baseline. For easier-to-treat patients, there are also reasons to be cautious regarding treatment intensification. In most hypertension studies, on-treatment SBPs between 130 to 139 mm Hg are associated with the lowest frequency of CV events (except stroke) compared with values above and below this range (6). In patients with hypertension and CAD, a J-shaped relationship has been observed with higher incidence of myocardial infarction seen at lower diastolic BP. In several studies, the on-treatment SBP associated with the lowest risk of CV endpoints was >140 mm Hg (7).
The results of SPRINT are those of a single study conducted in a unique population that excluded subjects with diabetes, cerebrovascular disease, and drug-resistant hypertension. It included a high proportion of patients with mild CKD and many elderly people with well-controlled hypertension. It enrolled untreated individuals not classified as hypertensive by conventional criteria. Unlike patients cared for by most cardiologists, a relatively small proportion (16.7%) had established CV disease. The differing results of SPRINT and ACCORD, 2 studies of similar design conducted by the same research group evaluating the same BP targets, are likely due to the composition of the 2 patient populations. Although the SPRINT results are likely valid for the study as a whole, its therapeutic implications cannot be automatically applied to every patient who met the inclusion criteria. A patient may belong to a subgroup (e.g., patients with CAD) that made a very small statistical contribution to the overall results. It is possible that a study conducted exclusively in that subgroup would yield very different results.
It is important to recognize that the choice of SBP target as <120 mm Hg in SPRINT was arbitrary. It is unfortunate that the JNC-7 (Seventh Joint National Committee) target of <130/80 mm Hg, widely recommended for high-risk patients prior to ACCORD, has never been properly evaluated in clinical trials. In a perspective regarding the SPRINT trial, JNC-7 Chair, Dr. Chobanian, recommended the JNC-7 target of <130/80 mm Hg “for most patients who are over 50 years of age and do not have diabetes” (8). This makes sense, because at 3.26 years of follow-up in the SPRINT trial, the mean SBP was 121.5 mm Hg in the intensive-treatment group and 134.6 in the standard-treatment group. In view of residual uncertainty regarding optimal BP targets in many subgroups, it is not prudent to radically alter treatment in patients who have achieved SBP levels considered optimal on the basis of prior evidence. I favor the addition of 1 (only) additional agent from a different pharmacologic class without further pursuit of SBP <120 mm Hg. In the event of treatment-emergent side-effects, the previous regimen should be reinstituted. For patients at increased risk of stroke (e.g., Asians), adherence to the SPRINT SBP target of <120 mm Hg is recommended.
Several categories of untreated patients with SBP 130 to 139 mm Hg included in SPRINT are also candidates for treatment. In patients with CKD, CAD, left ventricular hypertrophy, and/or heart failure, use of appropriate class(es) of antihypertensive agents is justified, if not always mandated, by previous studies. The results of SPRINT reinforce evidence documenting the favorable effects of neurohormonal antagonists and other agents in the therapy of these conditions. Treatment should be instituted in accordance with the SPRINT protocol.
There is little evidence, however, to support routine antihypertensive therapy in adults ≥75 years of age with SBP >130 mm Hg. Placebo-controlled trials on which the treatment of hypertension in the elderly are based enrolled only subjects with baseline SBP ≥160 mm Hg (9). Although risk reduction in SPRINT for subjects ≥75 years of age was substantial (33%), the number of untreated patients must have been small, as 92% of participants were receiving antihypertensive drugs at baseline. Although the SPRINT results are consistent with the possibility of significant benefit, they must be considered preliminary and insufficient to mandate universal drug therapy. Treatment is definitely an acceptable option given the safety and tolerability of available drugs. Additional clinical trials specifically designed to evaluate the effects of BP reduction in older subjects with untreated SBP 130 to 160 mm Hg constitute an important public health priority.
Because of the small number of untreated patients studied, the results of SPRINT are also insufficient to mandate drug treatment for patients with SBP 130 to 139 mm Hg and a high Framingham risk score. The results of TROPHY (Trial of Preventing Hypertension) and 1 other study indicate that renin-angiotensin-aldosterone system inhibitors delay progression to hypertension (BP ≥140/90 mm Hg) when BP is in this range, although the studies were not statistically powered to evaluate endpoint reduction (10). Many physicians treat BP 130 to 139 mm Hg in high-risk individuals on the basis of epidemiological evidence of increased risk. The SPRINT findings are consistent with this practice, and treatment is a reasonable option. There is presently no justification for extending the findings of SPRINT to encompass the >25 million Americans >50 years of age with SBP >120 mm Hg and increased CV risk.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Gradman has reported that he has no relationships relevant to the contents of this paper to disclose.
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