Outcomes of Intensive Blood Pressure Lowering in Older Hypertensive Patients
Bavishi C, Bangalore S, Messerli FH. J Am Coll Cardiol. 2017;69(5):486–493.
Reviewers: Deborah Dubensky, MD1
- North American Partners in Anesthesia, Melville, NY; and Hofstra Northwell School of Medicine, Hampstead, NY
In 2014, the Eighth Joint National Committee (JNC 8) panel changed its recommended therapeutic target systolic blood pressure (SBP). It had previously recommended a target SBP of <140 mmHg; it has now relaxed this recommendation to a target of <150 mmHg in patients 60 years or older. However, there are experts and subsequent analyses that continue to recommend a target SBP of <140 mmHg. The recent release of the SPRINT-SENIOR trial fanned the flames of controversy by evaluating the more aggressive target of <120 mmHg in patients 75 years or older. This meta-analysis set out to re-evaluate the safety and efficacy of intensive blood pressure lowering in elderly hypertensive patients.
A systematic search was conducted for randomized controlled trials from 1965 to July 1, 2016, that compared intensive blood pressure lowering vs standard or liberal blood pressure lowering. Inclusion criteria are as follows:
- Patients were 65 years or older and hypertensive.
- Intensive blood pressure control was compared to more liberal control.
- Long-term data were collected on cardiovascular and safety outcomes.
Cardiovascular outcomes evaluated were
- major adverse cardiovascular events (MACE) (note that the definitions of MACE varied among the studies)
- cardiovascular mortality
- myocardial infarction (MI)
- heart failure.
Safety outcomes included serious adverse events and renal failure. Data analysis was performed on an intention-to-treat basis. Due to the heterogeneity of included trials, a
random-effects model was used as the primary analysis to examine relative risks and 95% confidence intervals. To avoid overly weighting the smaller studies, the results were confirmed by a fixed-effects model.
Out of 22 potential studies, only four met eligibility criteria, for a total of 10 857 patients. Mean follow-up was 3.1 years. Three studies called for a target SBP of <140 mmHg and one called for a target of <120 mmHg. In all studies, patients were 65 years or older; however, two looked at patients 70 or older and one at patients 75 or older. With intensive blood pressure control, the studies showed MACE was decreased by 29%, and there was a 33% reduction in cardiovascular mortality when compared to standard therapy. There also was a significant decrease in the risk of heart failure. The rates for both MI and stroke were lower in the intensive control groups; however, they did not reach statistical significance. There was no significant difference in renal failure or incidence of serious adverse events. However, there was moderate heterogeneity found for renal failure, and analysis by a fixed-effects model showed an increased risk of renal failure in the intensive blood pressure lowering groups. A meta-regression analysis showed a 3-percentage-point decrease in the risk of MACE for each 1 mmHg difference in mean SBP achieved between the two groups, and a similar result for cardiovascular mortality.
The JNC 8 panel’s recommendation of more liberal SBP control has been met with much criticism. It proposed that “setting a goal SBP of lower than 140 mmHg in this age group provides no additional benefit compared with a higher goal SBP of 140–160 mmHg or 140–149 mmHg.” However, the panel also recognized its supporting data as “low quality.” This meta-analysis demonstrated that although there was no significant decrease in MI or stroke, intensive SBP control was associated with a decrease in MACE as well as cardiovascular mortality that was proportional to the degree of SBP lowering.
Depending on how you analyze the data, intensive reduction in SBP can have up to a twofold increase in risk for renal failure. In the SPRINT-SENIOR trial, patients with pre-existing chronic kidney disease did not show any differences in composite renal outcomes whether they were randomized to the liberal or the intensive blood pressure lowering arms. However, in patients with normal baseline renal function, there was a higher incidence of composite renal outcomes in the intensive blood pressure lowering group. It is important to note that there was no significant difference in albuminuria among all participants.
Researchers felt that the greater use of diuretics, in combination with ACE inhibitors as well as angiotensin receptor blockers, may have resulted in more pronounced rises in serum creatinine. This effect usually is considered functional, reversible, and the result of pharmacologic alterations in intrarenal hemodynamics.
In conclusion, the authors have shown that intensive lowering of SBP leads to decreased MACE, cardiovascular mortality, and heart failure. However, data on adverse effects are limited, and point toward an increase in renal complications. The trials included a minimal number of patients with diabetes and pre-existing cardiovascular disease, did not account for frailty, and did not look at symptomatic hypotension and/or syncope. Additionally, in order to achieve lower SBPs, many of these elderly patients were on up to three drugs. The burden of polypharmacy as well as the potential for drug interactions is a real concern. Clinicians who are referencing these studies when treating hypertension in their elderly population should seriously consider all risks and benefits before adopting an intensive SBP lowering strategy.