Espeland M, A., Whelton P, K., Kostis J, B., et al. Predictors and Mediators of Successful Long-term Withdrawal From Antihypertensive Medications. Archives of Family Medicine 1999;8:228-36.
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/10333818
Kostis JB, Espeland MA, Appel L, et al. Does withdrawal of antihypertensive medication increase the risk of cardiovascular events? Trial of Nonpharmacologic Interventions in the Elderly (TONE) Cooperative Research Group. American Journal of Cardiology 1998;82:1501-08.
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/9874055
| Methods | Study design: Open-label randomized controlled study with a three-by-two-factorial design
Number of groups: Six groups |
| Participants | Number of participants: 975 randomized
· Overweight people with weight loss: 27 enrolled · Overweight people with weight loss and sodium reduction: 23 enrolled · Overweight people with sodium reduction: 23 enrolled · Normal weight people with sodium reduction: 28 enrolled · Overweight persons with usual care: 21 enrolled* · Normal weight people with usual care: 42 enrolled* Age: 65.8 ± 4.6 years Sex: 509 female, 466 male Participants with dementia: No Inclusion criteria: · Average baseline systolic BP 145 mm Hg · Average diastolic BP 85 mm Hg on one medication · Willingness to participate in all aspects of the study · Independence in activities of daily living · Capacity to alter diet and physical activityby the requirements of any TONE intervention as evaluated by TONE intervention staff · Approval from the participant’s personal physician · Treated with two antihypertensive medications were eligible for recruitment as long as they met BP eligibility criteria after step-down from 2 to 1 medication – (For practical purposes, combination drugs consisting of a diuretic and non-diureticagent were considered to be a single medication) Exclusion criteria: · History of a heart attack or stroke within the preceding 6 months · Current angina pectoris · Congestive heart failure · Insulin-dependent diabetes mellitus · Serious psychiatric or physical illness · Unexplained or involuntary weight loss 10 pounds during the previous year · Body mass index >21 kg/m2 or < 33 kg/m2 (men) or < 37 kg/m2(women) · High creatinine levels (2.0 mg/dl) · Hyperkalemia (5.5 mmol/L) · Hyperglycemia (non-fastingglucose 260 mg/dl) · Anemia (c 11 g/dl) Country: United States of America Setting: Community – four clinical sites |
| Interventions | Medicine: Antihypertensives
Withdrawal schedule: Not described Comparator: Weight loss for overweight participants, reduced sodium intake, and usual care |
| Outcomes | Predictors of successful deprescribing
Cardiovascular events Reported rates of cardiovascular events The probability of remaining normotensive without receiving antihypertensive medication |
| Dates | Dates: September 1992 through April 1994
Follow-up duration: 60 months |
| Funding sources | National Institutes of Health, National Heart, Lung, and Blood Institute grants R01-HL48641, R01-HL48642 K08-HL02642 and National Institute on Aging grants R01-AG09773, R01-AG09799, R01-AG09771 and R03-HL60197. |
| Notes | Espeland and Kostis report on the same study.
*For the analysis, we have used the overweight-usualcare and the normal weight-usual care groups. |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Unclear risk | Not described. |
| Allocation concealment (selection bias) | High risk | Open study. |
| Blinding of participants and personnel (performance bias) | High risk | Open study |
| Blinding of outcome assessment (detection bias) | High risk | Open study |
| Incomplete outcome data (attrition bias) | High risk | As-treatedanalysis. The reason for withdrawals not reported. |
| Selective reporting (reporting bias) | High risk | A priori published protocol.
In each separate paper, the paper reports the stated outcomes. However, multiple papers reportmany different aspects of the study beyond what was described in the original published protocol. |
| Other bias | Unclear risk | All six groups have medicines deprescribed as well as additional interventions (sodium restriction, weight loss, and sodium restriction combined with weight loss). This means that it is unclear to what extent the deprescribing affected the outcomes compared to the lifestyle modification. |
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