Therapy Scenario

You see a 75 year old patient referred to you by his GP because of raised blood pressure. His past medical history is remarkable for mild asthma but he is otherwise well. His GP has enclosed a note stating that the patient’s blood pressure has been 160-190/80-90 for the past 3 months. The patient’s wife is on an ACE-I and has had no adverse effects and the patient wondered if he could take it as well. You explain to the patient that evidence from trials suggest that diuretics and beta blockers should be used as the initial treatment strategy because they are known to decrease the risk of stroke. The patient asks to look at this evidence with you. You formulate the question, “In patients with isolated systolic hypertension, do diuretics decrease the risk of stroke and death?”

You start up Best Evidence, enter “hypertension” and “stroke” and you find the abstract and commentary for the randomised controlled trial assessing the prevention of stroke with antihypertensive therapy. The abstract and commentary look helpful so you decide to go to the library and copy the original article [JAMA 1991;265:3255-64.]

You make a follow-up appointment with your patient and tell him that you will discuss the evidence with him at that time.

– Is the evidence from this randomised trial valid?
– If valid, is this evidence important?
– If valid and important, can you apply this evidence in caring for your patient?

Completed Therapy Worksheet for Evidence-Based Geriatric Medicine

Citation

SHEP Co-operative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA 1991;265:3255-64.

Are the results of this single preventive or therapeutic trial valid?

Was the assignment of patients to treatments randomised?
And was the randomisation list concealed?
Yes
Were all patients who entered the trial accounted for at its conclusion?
And were they analysed in the groups to which they were randomised?
Yes
Were patients and clinicians kept “blind” to which treatment was being received?
Yes – but may have been some unblinding because more of diuretic patients received potassium supplements
Aside from the experimental treatment, were the groups treated equally?
Yes
Were the groups similar at the start of the trial?
Yes – although some slight difference between groups in limitation of activities of daily living

Are the valid results of this prognosis study important?

Sample Calculations
Occurrence of diabetic neuropathy Relative Risk Reduction (RRR) Absolute Risk Reduction (ARR) Number Needed to Treat (NNT)
Usual Insulin
Control Event Rate (CER)
Intensive Insulin
Experimental Event Rate (EER)
(CER – EER)/CER CER-EER 1/ARR
9.6% 2.8% (9.6%-2.8%)/9.6%
= 71%
9.6% – 2.8%
= 6.8%
[4.3% to 9.3%]
1/6.8%
= 15 pts
[11 to 23]

$$text{95% Confidence Interval (CI) on an NNT = 1 / (limits on the CI of its ARR)} \ = pm 1.96 sqrt{frac{mathit{CER} times (1-mathit{CER})}{text{# of control pts.}} + frac{mathit{EER} times (1-mathit{EER})}{text{# of exper. pts.}}} \ = pm 1.96 sqrt{frac{0.096 times 0.904}{730} + frac{0.028 times 0.972}{711}} \ = pm 2.4%$$

Relative Risk Reduction (RRR) Absolute Risk Reduction (ARR) Number Needed to Treat (NNT)
CER EER (CER – EER)/CER CER-EER 1/ARR
0.07 0.04 (0.07 – 0.04)/0.07
= 43%
0.03 33

Can you apply this valid, important evidence about a treatment in caring for your patient?

Do these results apply to your patient?
no, he is similar to those included in the trial.
How great would the potential benefit of therapy actually be for your individual patient?
Method I: f
$$text{Risk of the outcome in your patient, relative to patients in the trial. Expressed as a decimal: 1.0}\\[10pt] mathit{NNT}/mathit{F} \\ = 33/1 \\ = 33 \\ text{(NNT for patients like yours)}$$
Method II: 1 / (PEER x RRR)
$$text{Your patient’s expected event rate if they received the control treatment:} \\[10pt] mathit{PEER}:underline{qquad{} qquad{}}\\[10pt] 1 / (mathit{PEER} times mathit{RRR}) \\ = 1/underline{qquad{} qquad{}} \\ = underline{qquad{} qquad{}} \\ text{(NNT for patients like yours)}$$
Are your patient’s values and preferences satisfied by the regimen and its consequences?
Do your patient and you have a clear assessment of their values and preferences?
Needs to be assessed in each patient
Are they met by this regimen and its consequences?
Needs to be assessed in each patient

Hypertension – Therapy with diuretics and beta blockers decreases the risk of stroke

Clinical Bottom Line

Treatment of isolated systolic hypertension with diuretics and/or beta blockers decreases the risk of stroke in the elderly.

Citation

SHEP Co-operative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension.
JAMA 1991;265:3255-64.

Clinical Question

In a patient with hypertension, will therapy with diuretics decrease the risk of stroke and death?

Search Terms

“stroke” and “hypertension” in Best Evidence

The Study

• Double-blinded concealed randomised controlled trial with intention-to-treat.
• patients = 60 years with isolated systolic hypertension
• Control group (N = 2371; 2371 analysed): placebos
• Experimental group (N = 2365; 2365 analysed):
4 consecutive steps

• chlorthalidone 12.5 mg/d;
• increase to chlorthalidone 25 mg/d;
• addition of atenolol 25mg/d or reserpine 0.05 mg/d;
• increase to atenolol 50mg/d or reserpine 0.1 mg/d.
• Goal of therapy was SBP < 160 mm Hg and a reduction in SBP of at least 20 mmHg. Any patient with sustained SBP > 220 mmHg or DBP > 90 mmHg was given active treatment

The Evidence

Outcome Time to Outcome CER EER RRR ARR NNT
Stroke 5 years 0.067 0.044 34% 0.023 43
95% Confidence Intervals 15% to 54% 0.107 to 0.036 28 to 100
Deaths 5 years 0.090 0.102 -13% -0.012 -83
95% Confidence Intervals -32% to 5% -0.029 to 0.005 NNT = 209 to INF
NNH = 35 to INF