Hypertension in elderly patients

Drug treatment trial outcomes

A re-appraisal of the 2007 European Society of Hypertension guideline reviewed the achieved SBPs in the comparator arms of 9 important drug treatment trials in elderly patients.⁸ All but 2 achieved SBPs lower than 160 mm Hg in the active treatment groups but none achieved SBPs lower than 140 mm Hg. However, all showed benefit in clinical outcomes. Thus, evidence from these treatment trials supports a potential benefit from an SBP target of lower than 160 mm Hg but does not support an SBP target of lower than 140 mm Hg in elderly patients. A 2011 consensus document prepared by the American College of Cardiology Foundation and the American Heart Association (ACCF-AHA) states that in elderly patients, the generally recommended goal of BP lower than 140/90 mm Hg in patients without complications is based on expert opinion rather than on data from randomized controlled trials.²

Treat-to-target trial outcomes

Two recent treat-to-target trials have reported clinical outcomes in elderly patients.^9,10 Both showed no benefit in treating elderly patients to an SBP target of lower than 140 mm Hg compared with SBP targets lower than 150 and 160 mm Hg. A Japanese trial, VALISH (Valsartan in Elderly Isolated Systolic Hypertension Study),⁹ randomly assigned 3079 patients aged 70 to 84 years (mean age 76 years) with isolated systolic hypertension (SBP higher than 160 mm Hg, DBP lower than 90 mm Hg) to a target SBP of lower than 140 mm Hg or 140 to 149 mm Hg. Initial therapy in both groups was 40 to 80 mg of valsartan once a day with other medications, except angiotensin II type 1 blockers, added as necessary to achieve targets. Mean baseline BPs were approximately 170/82 mm Hg in both groups and achieved BPs were 137/75 mm Hg and 142/77 mm Hg in the 140 mm Hg and 140 to 149 mm Hg groups, respectively. After a median of 3.1 years there was no statistically significant difference between the 2 groups in the primary composite outcome of sudden death, fatal or nonfatal stroke, fatal or nonfatal myocardial infarction, death from heart failure, other cardiovascular death, hospitalization for cardiovascular disease, or renal dysfunction (10.6 events per 1000 patient-years vs 12.0 events per 1000 patient-years; hazard ratio 0.89, 95% CI 0.60 to 1.31, P = .383).

Published in 2008, JATOS (Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients) studied 4418 Japanese people aged 65 to 85 years (mean age 74 years).¹⁰ Patients had essential hypertension with SBPs of 160 mm Hg or higher while receiving no antihypertensive drugs or receiving the same drug or drugs for at least 4 weeks. They were randomized to an SBP target of less than 140 mm Hg or 140 to 159 mm Hg. The main initial or add-on therapy was a calcium channel blocker, 20 to 60 mg of efonidipine, but other common antihypertensive drugs were also used. Mean baseline BP was 172/89 mm Hg in both groups, and achieved BPs were 136/75 mm Hg versus 146/78 mm Hg in the less than 140 mm Hg and 140 to 159 mm Hg groups, respectively. After 2 years (the prespecified trial duration), there was no statistically significant difference between the 2 SBP target groups in the primary composite outcome of stroke, cardiac and vascular disease, and renal failure (4.3% vs 4.3%) or withdrawal from adverse events (1.6% vs 1.6%).

The VALISH and JATOS studies have limitations. In both studies, fewer efficacy outcome events occurred than were predicted, with the result that both studies were underpowered. Nevertheless, the results were consistent. In addition, only about 15% of subjects had existing cardiovascular disease, so the studies do not provide information about SBP targets in patients with target organ damage.

No evidence to support treating to target

Another trial, HYVET (Hypertension in the Very Elderly Trial),¹¹ is sometimes used to suggest a SBP treatment target of 150 mm Hg in very elderly patients.² In HYVET, 2 groups of patients, all 80 years of age or older with SBPs at or higher than 160 mm Hg, were assigned a target SBP and DBP of less than 150 mm Hg and less than 80 mm Hg, respectively. However, one group received 1.5 mg of indapamide with or without 2 or 4 mg of perindopril to reach this target, while the other group received a placebo. In the 2 groups, BPs went from a mean of 173/91 mm Hg to 144/78 mm Hg versus 159/84 mm Hg in the treatment and placebo groups, respectively. The study was planned for 5 years but was stopped after a mean of 2.1 years because of a reduction in total mortality (12.3% vs 10.1%, absolute risk reduction 2.2%, relative risk reduction 18%, number needed to treat 46, 95% CI 24 to 637, P = .02). There was no statistically significant difference between the groups in the primary outcome of stroke. While HYVET does provide evidence of benefit from treating hypertension in very elderly patients with indapamide and perindopril, it does not provide evidence to support treating to a specific target.

While VALISH might not have been published in time to influence North American recommendations, current consensus documents and guidelines do not reflect the evidence from drug treatment trials and JATOS, and continue to recommend an SBP target of lower than 140 mm Hg in elderly patients.^2,7 The ACCF-AHA consensus document does state that for patients aged 80 years or older, achieved SBPs of 140 to 145 mm Hg, if tolerated, can be acceptable with exceptions. For example, if the patient has achieved an SBP lower than 150 mm Hg taking 1 or 2 medications with no problems, it is reasonable to aim for an SBP lower than 140 mm Hg “even though there is no firm evidence to support this target.”² Also, if the DBP is reduced to a “potentially dangerous” level of below 65 mm Hg, the lowest safely achieved SBP of 150 mm Hg or higher is acceptable.² This latter exception indicates potential harm from excessive lowering of BP in very elderly patients.

There is little evidence from randomized controlled trials to guide treatment targets in patients with target organ damage. In many important drug treatment trials in elderly patients, less than 15% of enrolled patients had cardiovascular disease, and patients with serious renal disease were excluded. In JATOS and VALISH, the 2 treat-to-target trials, only approximately 15% of patients had cardiovascular and renal target organ damage.^9,10 The ACCF-AHA consensus document states there is no evidence to support the use of BP targets lower than 130/80 mm Hg in elderly patients with conditions such as diabetes mellitus, chronic kidney disease, or coronary artery disease.²