Achieved Blood Pressure and Cardiovascular Outcomes in High-Risk Patients

Study Questions:

What are the risk associations over the whole spectrum of achieved systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the effect of changes in SBP and DBP on treatment at different baseline values in a broad spectrum of patients after stroke, myocardial infarction, and high cardiovascular risk?

Methods:

The investigators assessed the previously reported outcome data from high-risk patients aged ≥55 years with a history of cardiovascular disease, 70% of whom had hypertension, from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination, with a median follow-up of 56 months. Detailed descriptions of randomization and intervention have already been reported. They analyzed the associations between mean blood pressure achieved on treatment; prerandomization baseline blood pressure; or time-updated blood pressure (last on-treatment value before an event) on the composite outcome of cardiovascular death, myocardial infarction, stroke, and hospital admission for heart failure; the components of the composite outcome; and all-cause death. Analysis was done by Cox regression analysis, ANOVA, and χ2.

Results:

In ONTARGET, 25,127 patients known to be tolerant to angiotensin-converting enzyme (ACE) inhibitors were randomly assigned after a run-in period to oral ramipril 10 mg/day (n = 8,407), telmisartan 80 mg/day (n = 8,386), or the combination of both (n = 8,334). In TRANSCEND, 5,810 patients who were intolerant to ACE inhibitors were randomly assigned to oral telmisartan 80 mg/day (n = 2,903) or placebo (n = 2,907). Baseline SBP ≥140 mm Hg was associated with greater incidence of all outcomes compared with 120 mm Hg to <140 mm Hg. By contrast, a baseline DBP <70 mm Hg was associated with the highest risk for most outcomes compared with all DBP categories ≥70 mm Hg. In 4,052 patients with SBP <120 mm Hg on treatment, the risk of the composite cardiovascular outcome (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.03–1.26), cardiovascular death (1.29; 1.12-1.49), and all deaths (1.28; 1.15-1.42) were increased compared with those in whom SBP was 120-140 mm Hg during treatment (HR, 1 for all outcomes; n = 16,099). No harm or benefit was observed for myocardial infarction, stroke, or hospital admission for heart failure. Mean achieved SBP more accurately predicted outcomes than baseline or time-updated SBP, and was associated with the lowest risk at approximately 130 mm Hg, and at 110-120 mm Hg, risk increased for the combined outcome, cardiovascular death, and all-cause death except stroke. A mean DBP <70 mm Hg (n = 5,352) during treatment was associated with greater risk of the composite primary outcome (HR, 1.31; 95% CI, 1.20-1.42), myocardial infarction (1.55; 1.33-1.80), hospital admission for heart failure (1.59; 1.36-1.86), and all-cause death (1.16; 1.06-1.28), than a DBP 70-80 mm Hg (14,305). A pretreatment and mean on-treatment DBP of about 75 mm Hg was associated with the lowest risk.

Conclusions:

The authors concluded that very low blood pressure achieved on treatment was associated with increased risks of several cardiovascular disease events.

Perspective:

This study reports that in a population of patients with cardiovascular disease, with a high prevalence of hypertension, most of whom were taking antihypertensive medication, the lowest risk for the composite primary cardiovascular outcome and all its components was observed at achieved SBP between 120-140 mm Hg. Furthermore, a significantly higher risk was observed for cardiovascular death, hospital admission for heart failure, and all-cause death when SBP was greatly reduced. DBP followed a similar pattern with low DBP (<70 mm Hg) associated with a higher risk of myocardial infarction and hospital admission for heart failure. It appears that in some patients at low SBP on treatment, blood pressure medication might have to be reduced in number or dose to avoid adverse outcomes.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Blood Pressure, Blood Pressure Determination, Heart Failure, Hypertension, Hypotension, Myocardial Infarction, Ramipril, Primary Prevention, Risk Factors, Stroke, Treatment Outcome


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