Publications of the Week, July 28

Intensive versus standard blood pressure control

For a McMaster Perspective interview with Dr Anna Mathew on the results of the SPRINT trial, click here.

Background: In patients with hypertension, pharmacologic blood pressure–lowering therapy is widely used to prevent end-organ damage that can manifest clinically as ischemic or hemorrhagic stroke, an acute coronary syndrome, congestive cardiomyopathy, hypertensive retinopathy or nephropathy, and peripheral arterial disease (PAD). The long-standing aim of antihypertensive strategies is to identify optimal blood pressure–lowering targets that minimize micro- and macrovascular complications while simultaneously minimizing the risk of drug-related adverse effects.

Methods: The SPRINT (Systolic Blood Pressure Intervention Trial) randomly allocated 9361 patients aged ≥50 years with a systolic blood pressure ≥130 mm Hg and ≥1 cardiovascular risk factor (coronary artery disease, PAD, left ventricular hypertrophy, renal insufficiency [eGFR, 20-59 mL/min/1.73 m²], ≥15% 10-year risk of cardiovascular disease [based on Framingham cardiovascular risk score], or age ≥75 years) but without diabetes or prior stroke to an intensive blood pressure–lowering strategy, with a target systolic blood pressure <120 mm Hg, or to standard blood pressure lowering, with a target systolic blood pressure <140 mm Hg. The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, decompensated heart failure, or cardiovascular death.

Results: After a median 3.33 years of patient follow-up, the annual rate of the primary outcome was significantly lower in the intensive blood pressure lowering group than in the standard blood pressure lowering group: 1.77% versus 2.40% (hazard ratio [HR], 0.73; 95% CI, 0.63-0.86), as was the annual rate of all-cause mortality: 1.06% versus 1.41% (HR, 0.75; 95% CI, 0.61-0.92). However, intensive blood pressure lowering was associated with more frequent hypotension (0.7% vs 0.4%; P = .001), syncope (0.6% vs 0.5%; P = .07, hyponatremia (1.3% vs 0.7%; P < .001), and acute kidney injury (1.3% vs 0.8%; P < .001). When trial and posttrial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and harm, but rates of heart failure no longer differed between treatment groups.

Conclusions: The authors concluded that among patients at increased cardiovascular risk, targeting a systolic blood pressure <120 mm Hg was associated with an increased incidence of adverse events but with lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure <140 mm Hg.

McMaster editors’ comment: The landmark SPRINT trial represents a major paradigm shift in the management of patients with hypertension. Its application to individual patients will require careful clinical monitoring and titration of antihypertensive drugs to mitigate against adverse effects; moreover, achieving these twin goals may not be feasible in some patients. It is noteworthy that the SPRINT trial results are discordant with those of the smaller ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial in a narrower population of patients with diabetes mellitus, where intensive blood pressure lowering was not associated with improved cardiovascular outcomes.