PL 02-3 MANAGEMENT OF ELDERLY HYPERTENSION: WHOM TO TREAT AND HOW LOW TO GO

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Abstract

Age is the most powerful cardiovascular risk factor. Based on a meta-analysis of a million control patients in hypertension trials, the Clinical Trialists Collaboration has estimated that doubling of major cardiac and stroke events occurs with age increments of < 10 years (1). Data from the ACCOMPLISH trial, which will be presented at this ISH meeting for the first time, show that patients aged > 70 (mean: 75.2), compared with those < 70 (mean: 63.7), had a 2.82-fold greater event rate for cardiovascular death and a 2.31-fold greater event rate for stroke.

The benefits for treating hypertension in older people are well established. SHEP (2), the first study to enroll patients aged > 60 with isolated systolic hypertension (mean baseline systolic BP = 170mmHg) demonstrated that active treatment with chlorthalidone reduced systolic BP to 143mmHg and, compared with placebo (systolic BP = 155 mmHg), significantly reduced stroke by 36%. Similarly, in the SystEUR trial (3), also conducted in older patients with isolated systolic hypertension, the calcium channel blocker nitrendipine was significantly superior to placebo in preventing stokes.

The ACCOMPLISH trial has compared cardiovascular outcomes rates according to achieved systolic BPs. In patients aged < 70, the rates for the primary endpoint (CV death or non-fatal myocardial infarction or stroke) was significantly lower (by 39%) at < 140 than at > 140 mmHg; and was reduced by a further 27% at < 130 mmHg. For pts > 70, there was also a significant 34% reduction in events when systolic BP was reduced to < 140 mmHg, but there was no further benefit at < 130 mmHg. However, unlike SPRINT (discussed below), the ACCOMPLISH cohort included in a large proportion of diabetic patients in whom – both in analyses of ACCOMPLISH (4) as well as of the ACCORD trial (5) conducted in diabetic patients – CV outcomes were not improved when systolic BPs were reduced to targets lower than < 140 mmHg.

HYVET (6) was a landmark study in ambulatory community-dwelling hypertensive patients aged > 80 (average: 84). In patients randomised to active treatment, indapamide and perindopril were used to achieve a systolic target of < 150 mmHg (achieved: 143 mmHg). Compared with placebo, there was a significant 21% reduction in total mortality. Overall, treatment was well tolerated.

The SPRINT trial (7), performed in non-diabetic patients, has received much attention, particularly as its cohort included 30% of patients aged > 75. In this older cohort (average age: 80), intensive treatment (systolic target < 120 mmHg), compared with standard treatment (target < 140 mmHg) reduced systolic BP to 123.4 mmHg and significantly decreased the composite CV outcome by 34%, heart failure by 38% and total mortality by 33%. The treatment was well tolerated symptomatically, but there was a significant adverse effect on renal function. Similar decreases in renal function were also observed in ACCOMPLISH when systolic bps were outside the optimal 130–139 mmHg range (4).

It is important to note that BP in SPRINT was measured by an automated device with patients seated alone and unobserved by professional personnel. This method appears to provide systolic BPs around 5–10 mmHg lower than well-measured standard office BPs, so the achieved value of 123.4 mmHg in the older patient group in SPRINT corresponds to around 130 mmHg in usual clinical practice. Another issue in interpreting the SPRINT results is that the patients in the intensively treated group were significantly more likely to receive agents like renin-angiotensin system blockers, calcium channel blockers and thiazide-like diuretics that are known to exhibit CV benefits independent of BP reduction. So, how much of the benefit in the intensively treated group was due to its lower BP, and how much to the cardioprotective actions of the additional drugs?

Conclusions: We now know that treating patients into their 80 s, and possibly beyond, is well justified. Mortality and major cardiovascular outcomes are reduced. It is appropriate to recommend an office-measured systolic BP target of around 130 mmHg in older patients. Any of the major antihypertensive drug classes can be used: in particular calcium channel blockers, RAS blockers, and thiazides are indicated. In general, treatment in older patients is well tolerated, although it is wise to check for orthostatic symptoms in older patients and to monitor renal function when pursuing aggressive BP targets.

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