Journal Club – Chronic illness . Hypertension Diabetes Lipids. Hypertension. HOT study - Hypertension Optimal Study - Lancet 1998;351:1755 - 18,790 patients from 26 countries (Europe, N. & S. America, Asia) - Age 50-80, mean=61 - Started 1992, ended 1997. Hot Study – con’t. Aim
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- Hypertension Optimal Study
- Lancet 1998;351:1755
- 18,790 patients from 26 countries (Europe, N. & S. America, Asia)
- Age 50-80, mean=61
- Started 1992, ended 1997
Recommend Aspirin if 10 year CVD risk >15%
(as calculated from Sheffield table or Joint British coronary risk chart)
Systolic Hypertension in the Elderly Program
To determine if anti-HT drug treatment reduces the risk of stroke (fatal & non-fatal) in men and women with isolated systolic hypertension, aged >60.
Because up until 1990, trials had only been admitting pts with high Diastolic BP, and ignoring systolic reading.
And more epidemiology studies were showing a more robust relationship b/w systolic BP and mortality, esp. in elderly
Study design: Randomised, double-blinded, placebo-controlled.
Patients: 4736, from US mainly. Mean age 72
SBP= 160-219 mmHg
DBP= <90 mmHg
Follow-up: 4.5 years
Treatment: Chlorthlidone, Atenolol, Respine.
1) Treatment group:
Average SBP=143 mmHg, DBP 68
Risk of Stroke= 5.2%
2) Placebo group:
Average SBP=155 mmHg, DBP 72
Risk of Stroke= 8.2 %
A)Relative risk (RR) of Stroke = 0.64 (p=0.0003)
B)RR of Non-fatal MI = 0.73 (p=?)
C)RR of Major CVS events = 0.68 (p=?)
- Active HT treatment was significantly associated with decreased use of CABG and PTCA in patients <75 years with IHD.
To determine whether drug treatment of HT is beneficial in men/women aged 70-84 years, and to evaluate drug tolerance, and its effect on Cardiac, Cerebrovascular and total mortality.
Randomised, double-blinded, placebo-controlled.
1627 men and women (812 active Rx, 815 placebo), aged 70-84 years.
Mean = 25 months
Atenolol, Metoprolol, or Pinolol, or combination of Amiloride & Hydrochlorothiazide.
(Target BP <160/<95)
Treatment Group: mean BP 167/87 mmHg
Placebo Group: mean BP 186/96 mmHg
47% reduction in fatal and non-fatal strokes
43% reduction in total mortality
(p=0.0081and 0.0079 respectively)
Placebo gp: 132 complication endpoints – (CHF, BP>230/120, TIA etc…)
Treatment Gp; 40 complication endpoints only
(The effect became more pronounced as the study progressed)
- Beneficial effects of anti-HT drugs treatment were demonstrable up to age 84 (entire age range) and women were benefited at least as much as men.
N.B. The study was prematurely discontinued because it was unethical to placebo group patients.
Similar to STOP study (because it was really “stopped”!)
similar patients background (age 70-84), number=6614.
similar background (Swedish),
similar design (double-blinded, randomised,placebo-controlled)
But comparing the effects of 3 groups of anti-HT drugs –
2) Ca-antagonist +/- B-blocker
3) ACEI +/- hydrochlorothiazide
- Fatal stroke
- Fatal MI
- Fatal Cardiovascular disease
- Old and new antihypertensive drugs were similar in prevention of CVS mortality and major events.
In early 1990’s, the DCCT clearly showed that tight glycaemic control with intensified INSULIN therapy dramatically reduces Microvascular complications in TYPE I DM patients, but not difference in macrovascular disease
It achieved 2% reduction in median HbA1c compared with conventional therapy.
Long term follow up of these patients were published (NEJM 2000;342:381) and these benefits persist.
But it was associated with 3-fold rise in the risk of severe hypoglycaemia. This has raised the concern about the safety of intensified insulin therapy in usual clinical practice.
Until now, the DCCT results were generalised to patients with type 2 DM, without strong direct evidence in this group.
Largest Type II DM studies ever:
Started in 1977
Over 5,000 patients
The main clinical features were published in five papers
UKPDS 33 and 34 (Lancet 1998;352:837-53, 854-65)
UKPDS 38, 39, 40 (BMJ 1998;317:703-26)
Three clinically questions aimed at:
Compared the effects of intensified blood glucose control with conventional treatment over 10 years in approximately 4000 relatively young patients with newly diagnosed type 2 DM.
Design: Multicenter, randomised, controlled trial with median follow up of 10 years.
Intervention: intensive therapy vs conventional therapy
Outcome measures: sudden death, hyper/hypo-glycaemia, CVS events, amputation, stroke, vitreous hemorrhage, angina, CHF, renal failure, blindness, etc…, death (all cause).
Median HbA1c level were significantly lowered in intensive group than in conventional group. (7.0% vs 7.9%)
25% risk reduction for microvascular complications
No difference for macrovasculat events, all-cause mortality, and DM-realted death.
Lower HbA1c level
Reduces all-cause mortality
Less hypoglycaemic episodes than intensive treatment group
Support the choice of Metformin for obese type 2 DM patients.
Lower mean BP in tight control group
24% reduced risks for developing any DM-related complications
32% reduced risk of mortality
44% reduced risk of stroke
34% reduced risk of macrovascular disease
37% reduced risk of microvascular disease
56% reduction in heart failure
NNT 10 yrs to prevent any complication=6
NNT 10 yrs to prevent one DM-related death= 15
758 – tight control of BP
400 – captopril
358 – atenolol
- Captopril and Atenolol were equally effective in controlling BP to mean 144/83
- Both were equally effective in reducing risk of macrovascular endpoints, similar reduction in DM-related death
- Mean weight gain in atenolol group=3.4kg vs 1.6kg
Tight BP control in type 2 DM patients – substantially reduced the costs of complications, increased the interval without complications, and had a cost-effectiveness ratio that compares favourably with many accepted health-care program.
1) 4S study 2) CARE study
3) LIPID study 4) VA-HIT
1) Helsinki heart study 2)WOSCOPS
3) AFCAPS/TexCAPS 4) BMJ –meta-analysis
- HDL increased by 10%, TG reduced by 35%, LDL reduced by 9%
- Reduction of relative risk of major CHD events was 34% (esp. combined high TG & Cholesterol)
- LDL reduced by 26%, T.Chol by 26%.
- Non-fatal MI reduction by 31% (RR), fatal MI by 33%, all-cause mortality reduction by 22%.
- LDL reduction 25%, HDL raised 6%
- reduced incidence of MI (RR 0.6), Angina (RR 0.68), Coronary events (RR 0.75)