You might be interested in…Hypertension

Hypertension (Part 2)
Hypertension treatment guidelines have historically recommended initial treatment with a single blood pressure (BP)–lowering agent. However, more recently, guidelines have generally recommend starting with dual combinations for many or most adults with hypertension and lower BP targets to significantly reduce the risk of cardiovascular (CV) events.

This international, randomized, double-blind, placebo-controlled, parallel-group trial1 enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a two-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154 mm Hg.

Dr Ray O’Connor

Participants were randomized in a 2:2:1 ratio to GMRx2 1/4 dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 1/2 dose (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week four, and primary safety outcome was treatment discontinuation due to an adverse event.

A total of 295 participants (mean age: 51 years; 56 per cent female) were randomized and 96 per cent completed the trial. Baseline mean home BP was 139/86 mm Hg and clinic BP was 138/86 mm Hg after placebo run-in. The results showed that placebo-corrected least square mean differences in home SBP at Week 4 were -7.3 mm Hg for GMRx2 1/4 dose and -8.2 mm Hg for GMRx2 1/2 dose.

At Week 4, clinic BP control (<140/90 mm Hg) was 37 per cent, 65 per cent, and 70 per cent for placebo, GMRx2 1/4 dose, and GMRx2 1/2 dose, respectively. The authors’ conclusion was that in a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo.

The important caveat here is that the trial was funded by and the investigators employed by the group making these particular drug combination pills. I would prefer to see these findings independently verified by a group that has no link to the pharma industry.

Elevated systolic blood pressure is the most common coexisting condition among patients with diabetes. It increases the risk of cardiovascular disease (CVD) among patients with diabetes, and it constitutes the most modifiable risk factor for cardiovascular disease in these patients.

The authors of this randomised controlled trial2 enrolled patients 50 years of age or older with type 2 diabetes, elevated systolic blood pressure, and an increased risk of CVD at 145 clinical sites across China. Patients were randomly assigned to receive intensive treatment that targeted a systolic blood pressure of less than 120 mm Hg or standard treatment that targeted a systolic blood pressure of less than 140 mm Hg for up to five years.

The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, treatment or hospitalization for heart failure, or death from CV causes. 12,821 patients (6,414 patients in the intensive-treatment group and 6,407 in the standard-treatment group) were enrolled. 5,803 (45.3 per cent) were women; the mean age of the patients was 63.8 years.

At one year of follow-up, the mean systolic blood pressure was 121.6 mm Hg in the intensive-treatment group and 133.2 mm Hg in the standard treatment group. During a median follow-up of 4.2 years, primary-outcome events occurred in 393 patients (1.65 events per 100 person-years) in the intensive-treatment group and 492 patients (2.09 events per 100 person-years) in the standard-treatment group (hazard ratio, 0.79; P<0.001).

The incidence of serious adverse events was similar in the treatment groups. However, symptomatic hypotension and hyperkalemia occurred more frequently in the intensive-treatment group. Thus, aiming for SBP of 120 mmHg seems optimal in those diagnosed with type 2 diabetes mellitus.

What about aiming for less intensive BP targets in older adults (aged >65 years)? It has been argued that the risk and benefit of antihypertensive therapy can be expected to vary across populations, and some observational evidence suggests that older adults who are frail might have better health outcomes with less aggressive BP lowering. Current clinical practice guidelines are inconsistent in target BP recommendations for older adults, with systolic BP targets ranging from < 130 mmHg to < 150 mmHg.

The objective of this systematic review and meta-analysis3 by the Cochrane collaboration was to assess the effects of a less aggressive blood pressure target (in the range of < 150 – 160 / 95 – 105 mmHg), compared to a conventional or more aggressive BP target (of < 140/90 mmHg or lower) in hypertensive adults, 65 years of age or older.

The authors found that there is high-certainty evidence that the lower BP target reduces stroke, and moderate-certainty evidence that the lower BP target likely reduces serious CV events. The effect on all-cause mortality is unclear (low-certainty evidence), and the lower BP target likely does not increase withdrawals due to adverse effects (moderate-certainty evidence). They conclude that although additional research is warranted in those who are 80 years of age and older, and those who are frail (in whom risks and benefits may differ), conventional BP targets may be appropriate for the majority of older adults.

Deprescribing of antihypertensive medications is recommended for some older patients with low blood pressure and frailty. Earlier work by this OPTiMISE group has shown that this deprescribing can be achieved with no differences in blood pressure control at three months compared with usual care. The aim of this follow on randomised controlled trial4 by the same group was to examine effects of deprescribing on longer-term hospitalisation and mortality.

The trial enrolled participants from 69 general practices across central and southern England. Participants aged 80 years or older, with systolic blood pressure less than 150 mm Hg and who were receiving two or more antihypertensive medications, were randomly assigned (1:1) to antihypertensive medication reduction (removal of one antihypertensive) or usual care. 569 participants were randomly assigned. Of these, 564 (99 per cent; intervention=280; control=284) were followed up for a median of 4⋅0 years.

Participants had a mean age of 84⋅8 years at baseline and 273 (48 per cent) were women. Medication reduction was sustained in 109 participants at follow-up (51 per cent of the 213 participants alive in the intervention group). The conclusion was that half of participants sustained medication reduction with no evidence of an increase in all-cause hospitalisation or mortality. These findings suggest that an antihypertensive deprescribing intervention might be safe for people aged 80 years or older with controlled blood pressure taking two or more antihypertensives.

What about the effect of deprescribing on cognitive function? The aim of this cohort study5 was to investigate the association of deprescribing antihypertensive medication with changes in cognitive function in nursing home residents.

The study included Veteran Administration (VA) long-term care residents aged 65 years or older with stays of at least 12 weeks from 2006 to 2019. Eligible residents with stable medication use for four weeks were classified into deprescribing or stable user groups and followed for two years or until death or discharge for intention-to-treat (ITT) analysis.

Cognitive function measurements during follow-up were analysed. Their findings were that of 45,183 long-term care residents, 12,644 residents (mean age 77.7 years; 329 [2.6 per cent] females and 12,315 [97.4 per cent] males) and 12,053 residents (mean age 77.7 years; 314 [2.6 per cent] females and 11,739 [97.4 per cent] males) met eligibility for ITT and per-protocol analyses respectively. The authors concluded that deprescribing was associated with less cognitive decline in nursing home residents, particularly those with dementia. They suggested that more data are needed to understand the benefits and harms of antihypertensive deprescribing.

Orthostatic hypertension, an elevation in blood pressure after standing, is an emerging risk factor for several adverse health outcomes, including cardiovascular disease, stroke, kidney disease, and cognitive impairment. It is defined as an increase in systolic blood pressure ≥20 mm Hg or diastolic blood pressure ≥10 mm Hg after changing from sitting to standing. In this systematic review and meta analysis,6 the authors used data from nine randomized trials of >30,000 participants. They showed that more intensive blood pressure treatment reduces the occurrence of orthostatic hypertension. Many of the included trials used first line antihypertensive agents, suggesting that common approaches for seated hypertension may also be used to treat orthostatic hypertension.

References:

1. Rodgers A et al. Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination Compared With Placebo for Initial Treatment of Hypertension. J Am Coll Cardiol 2024 Dec 10;84(24):2393-24035. https://doi.org/10.1016/j.jacc.2024.08.025
2. Bi Y et al. Intensive Blood-Pressure Control in Patients with Type 2 Diabetes. N Engl J Med 2025 Mar 27;392(12):1155-1167. doi: 10.1056/NEJMoa2412006
3. Falk JM et al. Higher blood pressure targets for hypertension in older adults. Cochrane Database of Systematic Reviews 2024, Issue 12. Art. No.: CD011575. doi: 10.1002/14651858.CD011575.pub3
4. Sheppard J et al. Effect of antihypertensive deprescribing on hospitalisation and mortality: long-term follow-up of the OPTiMISE randomised controlled trial. Lancet Healthy Longev 2024;5: e563–73 https://doi.org/10.1016/S2666-7568(24)00131-4
5. Jing B et al. Deprescribing of Antihypertensive Medications and Cognitive Function in Nursing Home Residents. JAMA Intern Med. doi:10.1001/jamainternmed.2024.4851. Published online September 23, 2024.
6. Juraschek S et al. Effects of intensive blood pressure treatment on orthostatic hypertension: individual level meta-analysis. BMJ 2025;388:e080507 http://dx.doi.org/10.1136/bmj-2024‑080507