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Table 2 Characteristics of the studies included in the NICE guideline and of the studies included in the current study

From: Anti-hypertensive drugs deprescribing: an updated systematic review of clinical trials

Study,
Catchment area
Study design Study population Exposure Outcomes Results
NICE Guidelines
 Freis et al., 1975 [18]
United States
Double-blind randomized clinical trial Adult veterans hospitalized prior to treatment for hypertension, with average diastolic blood pressure < 95 mmHg for 2 or more years and treated with anti-hypertensives for primary prevention for ≥2 years Discontinuation of anti-hypertensive drugs and allocation to placebo (N = 60)
vs.
Continuation of anti-hypertensive drugs
(N = 26)
- Cardiovascular mortality after 18 months of follow-up;
- Non-fatal congestive heart failure after 18 months of follow-up;
- Atrial fibrillation after 18 months of follow-up;
- Right bundle block after 18 months of follow-up
During the 18 months of follow-up, 51 people (85%) in the intervention group were removed from the trial: 42 (70%) because of return to increased arterial pressures and 6 (10%) because of major cardiovascular complications. Nine (15%) of the placebo patients remained normotensive.
 Greenberg et al., 1986 [19]
England
Open label randomized clinical trial Adult people with mild hypertension (diastolic blood pressure 90–109 mmHg) and treated with anti-hypertensive drugs for primary prevention for 5.5 years Discontinuation of anti-hypertensives (bendrofluazide or propanololol) (N = 783)
vs.
continuation of anti-hypertensives (bendrofluazide or propanololol) (N = 837)
Maintaining target blood pressure (diastolic blood pressure < 90 mmHg) after 2 years of follow-up 396 people (24.4%) completed the 2 year follow up.
Mean blood pressures rose- rapidly after the withdrawal of active treatment, and between nine months and one year after stopping treatment the antihypertensive effect almost disappeared. After stopping propranolol pressure tended to increase less quickly in older people than in younger.
 Maland et al., 1983 [20]
United States
Double-blind randomized clinical trial Adult living in the community, with mild hypertension (diastolic blood pressure average 90 mmHg or less for 1 year) and treated with anti-hypertensives for primary prevention for ≥1 year Discontinuation of anti-hypertensives (chlorthalidone, hydrothiazide, triamterene) and allocated to placebo (N = 31)
vs.
Continuation of anti-hypertensives (chlorthalidone, hydrothiazide, triamterene) (N = 31)
- Cardiovascular mortality after 1 year of follow-up
- Non-fatal myocardial infarction after 1 year of follow-up
- Transient ischaemic attack after 1 year of follow-up
- Return to hypertension (diastolic blood pressure > 95 mmHg) after 1 year of follow-up
59 people (95.2%) completed the 1 year follow up. Nine patients reverted to elevated blood pressure: eight from the placebo group and one from the active treatment group (p = 0.03). The average time to reversion was 27 weeks, with a range of 15 to 48 weeks.
Elevated pressures in all reverters returned to normotensive levels within 1 month of restarting the pre-trial medication at the dose-level previously used
Current study
 Sheppard et al., 2020 [21]
United Kingdom
Open label randomized clinical trial Patients aged ≥80 years with blood pressure < 150 mmHg and who had received ≥2 anti-hypertensives for ≥1 year.
Enrolled patients: 569
Medication reduction (N = 282 patients)
vs.
Standard clinical practice (N = 287 patients)
- Maintaining systolic blood pressure < 150 mmHg after 12 weeks of follow-up;
- % of patients in the intervention group who maintained the reduced therapeutic regimen;
- Differences between the two groups in frailty, quality of life, adverse events and changes in blood pressure over 12 weeks.
- 12-week follow-up: 229 (86,4%) patients in the intervention group and 236 (87,7%) patients with standard therapy had blood pressure < 150 mmHg (RR = 0.98 [97.5% 1-sided CI, 0.92- ∞]);
- Medication reduction was maintained in 187 (66.3%) patients in the intervention group;
- At week 12, mean blood pressure was 133.7 (95% CI, 131.7–135.6) mmHg in the intervention group and 130.8 (95% CI, 128.9–132.7) mmHg in the control group;
- No significant differences were found between the two groups in terms of frailty, quality of life and adverse events.
 Luymes et al., 2018 [22]
The Netherlands
Open label randomized clinical trial Patients aged from 40 to 70 years, without established cardiovascular diseases and who had been using anti-hypertensive or lipid-lowering drugs for at least 1 year Medication reduction (N = 492 patients)
vs.
Usual care (N = 575 patients)
- Increase in participants’ predicted 10-year cardiovascular risk after 2 years of follow-up;
- Systolic and diastolic blood pressure differences between the two groups
A 2-year increase in cardiovascular risk was observed in both groups (from 4.7 to 6.7% for the intervention group and from 5.1 to 7.0% for the usual care group). Since only a difference of 0.1 (95% CI: − 0.3 to 0.6) percentage points was detected, non-inferiority was established. Moreover, systolic and diastolic blood pressure was higher in the intervention group than in the usual care group (p-value < 0.01 for both comparisons).
  1. Abbreviations: CI confidence interval; NICE National Institute for Health and Care Excellence; OR odds ratio; RR relative risk