SPRINT: This Changes a Lot!
SPRINT is a “game changer.” Based on the main results, up to 16 million Americans (those meeting trial entry criteria) will benefit from more intensive blood pressure (BP) control than previously promulgated by guidelines (in particular, the recent Eighth Joint National Committee [JNC 8] recommendations). The trial was stopped earlier than expected as the primary composite outcome was significantly decreased after only slightly more than 3 years. The composite event reduction appears to be chiefly derived from decreases in cardiovascular and all-cause mortality, as well as from hospitalizations for congestive heart failure. It is important to highlight that few hypertension trials have demonstrated a reduction in mortality, and this is an outstanding (and perhaps surprising) aspect of SPRINT, whereas stroke risk unexpectedly only trended to be decreased despite the substantially lower achieved BPs. It is also remarkable that the overall benefits occurred across all demographic strata, including higher and lower baseline BPs (even those starting <132 mm Hg systolic), age >75 years or less, and gender and race in this high-risk population. Moreover, only 2.8 medications were required to achieve the aggressive level (~121 mm Hg) of carefully measured (using validated automated devices) clinic systolic BPs. This provides hope for the possibility of achieving this degree of control using a similar rational therapeutic strategy in the population at large. However, severe and/or resistant hypertensive patients were excluded from SPRINT; as with any clinical trial, various selection biases may have altered the cohort somewhat compared to the “real-world” hypertensive population.
We recognize of course that many unanswered questions remain. Important among them are those raised by the findings from the 24-hour ambulatory BP results, as well as the role that “masked hypertension” plays in predicted outcomes, particularly in the subgroup of patients who started with lower systolic BP levels (i.e., <132 mm Hg). Providers eagerly await these data, which should provide numerous important insights into the optimal management of hypertension. There is no data as of yet in regards to the potential benefits among lower-risk hypertensive patients because SPRINT was really a study of “high-risk” individuals. The risks versus long-term benefits among adults less than age 50 years are also important to know, keeping in mind that the average age of participants in SPRINT was close to 68 years old. Patients with diabetes and those with previous strokes were deliberately excluded. However, given the findings from a recent sub-analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (referenced by the SPRINT investigators) as well as observations from recent stroke trials and meta-analyses, we believe the net benefits of aggressive BP lowering will likely apply to these populations as well. As more outcome trial evidence, including these landmark results from SPRINT, fill missing the pieces to the overall puzzle, it appears that the benefits of BP lowering will likely match the axiom observed from lipid-lowering trials. Risk reduction is proportional to both the magnitude of BP reduction and also the absolute baseline cardiovascular risk. In addition, Mendelian randomization trials and other data suggest that the duration of treatment is also critical with earlier control of BP yielding even larger magnitudes of risk reduction. Hopefully, creative studies will be able to address the much needed answer regarding the appropriateness of longer-term BP treatment among lower-risk patients for lifetime prevention.
Overall, we believe SPRINT was an unmitigated success and is a “practice-changing” trial. Should we lower the level of carefully measured clinic systolic BP at which we intensify therapy (even when it is already <140 mm Hg systolic)? Should we carefully target lower systolic BP goals to <120 mm Hg, while watching for important side effects such as hypotension and renal insufficiency? In high-risk elderly patients similar to the SPRINT cohort, our opinion is yes. We will change our practice in such a manner while keeping in mind that some degree of shared decision making on an individual basis must always be considered. Not every patient may be able to safely and prudently achieve these goals. Notwithstanding the important insights gained from SPRINT, more intensive control of systolic BP in high-risk hypertensive patients will require more frequent clinic visits, added medications, and possibly more creative, technology-driven assistance to health care providers. Given that hypertension remains the leading risk factor for premature morbidity and mortality worldwide, we believe the payoffs will be very real.
- Bress AP, Tanner RM, Hess R, et al. Generalizability of results from the Systolic Blood Pressure Intervention Trial (SPRINT) to the US adult population. J Am Coll Cardiol 2015 Nov 9. [Epub ahead of print]
- Wright JT, Williamson JD, Whelton PK, on behalf of the SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015 Nov 9. [Epub ahead of print]
Keywords: Ambulatory Care, Blood Pressure, Blood Pressure Determination, Cardiovascular Diseases, Decision Making, Demography, Diabetes Mellitus, Health Personnel, Hospitalization, Hypertension, Hypotension, Lipids, Masked Hypertension, Random Allocation, Renal Insufficiency, Research Personnel, Risk Factors, Risk Reduction Behavior, Secondary Prevention, Selection Bias, Stroke, Systole, Secondary Prevention
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