• Evidence from “drug treatment” trials [i.e., trials that randomize patients to different treatments such as comparing placebo to a drug or comparing one drug to another drug] indicates that there is benefit in treating healthy older adults with hypertension. The benefit of treating frail older adults is unknown.
  • Major trials enrolled elderly patients only if their SBP was above 160 mmHg. As such, evidence supports initiating pharmacotherapy at a SBP ≥160 mmHg. None of the randomized controlled “drug treatment trials” involving elderly patients achieved a SBP <140 mmHg in the active treatment group. Therefore, there is no evidence from randomized controlled trials that supports a SBP target of <140 mmHg for the elderly.
  • ‘Treat to target’ trials randomize subjects to two different SBP target goals, but the two groups are treated with the same or similar drugs. Two “treat to target” trials of elderly subjects achieved a SBP <140 mmHg, but there were no statistically significant differences in the primary outcome. Thus, “treat to target” studies also fail to support a SBP target of <140 mmHg for the elderly.
  • The benefit of adding a third medication to lower blood pressure has not been studied.
  • The characteristics of frailty make the potential benefits of strict blood pressure targets even less certain and increase the possibility of harm from adverse drug events. The only study of adults above the age of 80, HYVET, enrolled relatively healthy subjects and excluded individuals with orthostatic hypotension.

 Rationale: High risk due to previous stroke

  • Most of the studies reviewed above enrolled relatively healthy older adults.  Due to limited evidence, it is even more difficult to judge the potential benefit of lowering BP below 140 mmHg when frail individuals have a history of previous stroke compared to the possibility that medications will cause adverse effects (such as weakness, orthostasis, and falls). To consider treatment benefit with frailty, we valued trial outcomes that would impact quality of life.  Thus, a relevant outcome would be non-fatal stroke leading to disability. In contrast, the effect of treatment on mortality is difficult to evaluate when there are competing causes for death due to frailty, which makes a mortality outcome less meaningful for the frail.
  • In the PROGRESS trial9, individuals with a mean age of 64 years were treated with perindopril +/- indapamide.  The treatment group experienced decreased rates of disabling stroke, with a relative risk reduction of 38% and absolute risk reduction of 1.64% (2.7% vs 4.3%; NNT  61, [95% CI 39-139]) over almost 4 years, compared to placebo.  Based on an evaluation of the risk reduction for all strokes (fatal and non-fatal), the relative risk reduction was found to be similar across a range of baseline systolic pressures, but the absolute reduction was greater in the population with a mean blood pressure of 159/94 mmHg compared to the remainder of the population with a mean blood pressure of 136/79 mmHg.  This evidence is based on studies of younger patients in relatively good health; the extent to which these results can be extrapolated to older, frail adults is uncertain due to the timeline needed to achieve benefit and the added vulnerability of frailty, which could make treatment with medications riskier.
  • Another study of individuals with previous stroke and mean age of 66.1±8.6 years, PRoFESS,10 showed no benefit over 2.5 years in the primary outcome of stroke using telmisartan 80 mg daily compared to placebo.  This result is concordant with the PROGRESS trial, which failed to demonstrate a statistically significant reduction in stroke risk with single agent treatment.