Intensive blood pressure management in hypertensive patients at increased cardiovascular risk

EBM Focus - Volume 10, Issue 45

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Reference - SPRINT trial (N Engl J Med 2015 Nov 9 early online) (level 1 [likely reliable] evidence)

  • For patients with hypertension, current generally recommended systolic blood pressure target is < 140 mm Hg, though some evidence suggests lower targets may reduce the risk of adverse cardiovascular events.
  • In this trial, a systolic blood pressure target of < 120 mm Hg was associated with a decreased risk all-cause mortality, cardiovascular mortality, and heart failure compared to target of < 140 mm Hg in nondiabetic patients with hypertension and increased cardiovascular risk.
  • A systolic blood pressure target of < 120 mm Hg was also associated with increased risk of specific adverse events including hypotension, syncope, electrolyte abnormalities, and acute kidney disease or acute renal failure.

Guidelines for managing patients with hypertension generally recommend target systolic blood pressure < 140 mm Hg, but may vary slightly based on age and cardiovascular risk (JAMA 2014 Feb 5;311(5):507, NICE 2011 Aug:CG127, Can J Cardiol 2015 May;31(5):549). Previous trials have suggested that intensive antihypertensive therapy with lower systolic blood pressure targets might reduce the risk of adverse cardiovascular events, but the results have been inconsistent (Lancet 2009 Aug 15;374(9689):525, N Engl J Med 2010 Apr 29;362(17):1575, Heart 2013 May;99(9):601). To further investigate how blood pressure targets may affect cardiovascular outcomes, a recent randomized trial compared intensive therapy with systolic blood pressure target of < 120 mm Hg vs. standard therapy with systolic blood pressure target of < 140 mm Hg in 9,361 adults ≥ 50 years old with mean baseline systolic blood pressure 130-180 mm Hg and increased cardiovascular risk. Patients were excluded if they had diabetes, history of stroke, polycystic kidney disease, significant proteinuria in previous 6 months, symptomatic heart failure in previous 6 months, or left ventricular ejection fraction < 35%.

The primary composite outcome included myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, and cardiovascular death. At baseline, the mean blood pressure was 140/78 mm Hg with a mean of 1.8 antihypertensive agents per person. At median 3.26 years, mean systolic blood pressure was 121.5 mm Hg with intensive treatment vs. 134.6 mm Hg with standard treatment with mean 2.8 vs. 1.8 blood pressure medications/person, respectively. Comparing intensive therapy vs. standard therapy, the annualized rate of the primary outcome was 1.65% vs. 2.19% (p < 0.001, NNT 185 per year). There were consistent results across subgroup analyses stratified by baseline systolic pressure (≤ 132 mm Hg, 132-145 mm Hg, and ≥ 145 mm Hg). Cardiovascular mortality and heart failure were significantly reduced with intensive therapy, while there were no significant differences in the other components of the primary outcome. Intensive therapy was also associated with a significant reduction in annualized all-cause mortality (1.03% vs. 1.4%, p = 0.003, NNT 270 per year). While the overall rate of serious adverse events was not significantly different between groups, hypotension, syncope, electrolyte abnormalities, and acute kidney injury or renal failure all occurred at significantly higher rates in the intensive therapy group. There were no significant differences in adverse renal outcomes in patients with baseline chronic kidney disease, however.

This finding was consistent across all baseline systolic blood pressures measurement, suggesting that even patients with systolic blood pressure < 140 mm Hg who are considered well controlled may still derive benefit from more intensive treatment. It should be noted that the protocol required patients receiving standard therapy to have their medication reduced if their systolic blood pressure was consistently below 135 mm Hg. Most of these patients would not have had their medication reduced in a typical clinical setting and this protocol may have therefore increased the magnitude of benefit for intensive therapy in the subgroup of patients taken off potentially beneficial medications. Nonetheless, this approach created a clear distinction between the 2 treatment groups, allowing the effect of the lower target to be more evident. In contrast, the ACCORD BP trial found no significant differences in the composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke with intensive therapy with a systolic blood pressure target of < 120 mm Hg (N Engl J Med 2010 Apr 29;362(17):1575). Several factors may have contributed to this disparate result. First, the patient populations in these trials were fundamentally different. The ACCORD BP trial included patients with type 2 diabetes and a high risk for cardiovascular events while patients with diabetes were specifically excluded from this trial. There may be important differences in the needs of patients with diabetes compared to nondiabetic patients for the prevention of cardiovascular events that are not currently well understood. Second, while the ACCORD BP trial included > 4,000 patients, the observed rate of cardiovascular events in the standard therapy group was much lower than expected. The reduced rate of events suggests the trial may have been underpowered to adequately detect differences between the two blood pressure target groups. Finally, the current trial intended to follow patients for a mean of 5 years, but the trial was terminated early when the primary outcome exceeded the predefined stopping boundaries at 2 consecutive interim analyses. This left the trial with a median 3.26 years follow-up. This follow-up may not have been long enough to determine if these results would extend beyond a relatively short-term benefit. Overall, the results of this trial suggest that intensive blood pressure management targeting a systolic blood pressure of < 120 mm Hg decreases the risk of cardiovascular events and increases overall survival in patients with hypertension and other cardiovascular risk factors. However, the increased risk of certain adverse events should be weighed against the benefits when determining how best to manage individual patients.

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