Presentation on theme: "Journal Club – Chronic illness"— Presentation transcript:
1Journal Club – Chronic illness HypertensionDiabetesLipids
2Hypertension 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
3Hot Study – con’tAimAssess the relationship between Major Cardiovascular (CVS) Events with 3 targets DBPAssess whether low-dose Aspirin, added on anti-HT therapy, reduces CVS incidence.Study DesignRandomised, single-blinded (HT Rx) and double-blinded (Aspirin)Mean years – 3.8 years follow up
4HOT Study – con’t Treatment regimen HT drugs – including Felodipine 5mg QD, may add on ACEI, B-blocker, Hydrochlorothiazide if necessary.Divided into 3 target groups (DBP <90, <85, <80) – each group randomised to low-dose aspirin or not.ResultsThe lowest incidence of major CVS events: DBP82.6The lowest incidence of CVS mortality: DBP86.5No BP differences whether adding Aspirin or notNo J-curve relationship b/w CVS events and DBP
5HOT study – con’t Results: DM patients: a 51% reduction of CVS events if DBP was reduced from <90mmHg to <80mmHg.Aspirin reduced major CVS events by 15% and all MI by 36%. No effect on incidence of stroke pr fatal bleeds, but non-fatal bleeds were twice as common.
6HOT Study – con’t Optimal calculated BP = 139/83 mmHg British Hypertension Society Guidelines:Recommend Aspirin if 10 year CVD risk >15%(as calculated from Sheffield table or Joint British coronary risk chart)
7SHEP Study Systolic Hypertension in the Elderly Program Aim: 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.WHY?
8SHEP Study – con’tBecause 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
9SHEP study – con’tStudy design: Randomised, double-blinded, placebo-controlled.Patients: 4736, from US mainly. Mean age 72SBP= mmHgDBP= <90 mmHgFollow-up: 4.5 yearsTreatment: Chlorthlidone, Atenolol, Respine.
10SHEP study – con’t Results: 1) Treatment group: Average SBP=143 mmHg, DBP 68Risk of Stroke= 5.2%2) Placebo group:Average SBP=155 mmHg, DBP 72Risk 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=?)
11SHEP study – con’t Conclusion: - Active HT treatment was significantly associated with decreased use of CABG and PTCA in patients <75 years with IHD.
12STOP Hypertension Swedish Trial in Old Patients with HT (STOP study) AIM:To determine whether drug treatment of HT is beneficial in men/women aged years, and to evaluate drug tolerance, and its effect on Cardiac, Cerebrovascular and total mortality.
13STOP Study – con’t Study Design Randomised, double-blinded, placebo-controlled.Patients1627 men and women (812 active Rx, 815 placebo), aged years.Follow-upMean = 25 months
14STOP Study – con’t Treatment: Atenolol, Metoprolol, or Pinolol, or combination of Amiloride & Hydrochlorothiazide.(Target BP <160/<95)
15STOP Study – con’t Results Treatment Group: mean BP 167/87 mmHg Placebo Group: mean BP 186/96 mmHg47% reduction in fatal and non-fatal strokes43% reduction in total mortality(p=0.0081and 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)
16STOP Study – con’t Conclusion - 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.HT treatment in elderly is cost-effectiveN.B. The study was prematurely discontinued because it was unethical to placebo group patients.
17STOP 2 Study (Lancet 1999:354;1751)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 –1) B-blocker/Diuretics2) Ca-antagonist +/- B-blocker3) ACEI +/- hydrochlorothiazide
18STOP 2 Study – con’t Outcome measures: - Fatal stroke - Fatal MI - Fatal Cardiovascular diseaseResults & Conclusion- Old and new antihypertensive drugs were similar in prevention of CVS mortality and major events.
19Diabetes Landmark Studies Diabetes Control & Complications Trial (DCCT)UK Prospective Diabetes Study (UKPDS)
20DCCT – Diabetes 1996;45: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 diseaseIt achieved 2% reduction in median HbA1c compared with conventional therapy.
21DCCTLong 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.
22UKPDS Largest Type II DM studies ever: Started in 1977 Over 5,000 patientsThe main clinical features were published in five papersUKPDS 33 and 34 (Lancet 1998;352:837-53, )UKPDS 38, 39, 40 (BMJ 1998;317:703-26)
23UKPDS Three clinically questions aimed at: Intensive treatment gives a better long- term outcome?Are medicines giving more benefit or harm? (Sulphonylurea – toxic?, Insulin – athrogenic?)Tight BP control improves micro/macro-vascular outcomes?
24UKPDS - 33Compared 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
25UKPDS 33 – con’tOutcome measures: sudden death, hyper/hypo-glycaemia, CVS events, amputation, stroke, vitreous hemorrhage, angina, CHF, renal failure, blindness, etc…, death (all cause).Results:Median HbA1c level were significantly lowered in intensive group than in conventional group. (7.0% vs 7.9%)25% risk reduction for microvascular complicationsNo difference for macrovasculat events, all-cause mortality, and DM-realted death.
26UKPDS 34Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 DM.Results:Lower HbA1c levelReduces all-cause mortalityLess hypoglycaemic episodes than intensive treatment groupConclusion:Support the choice of Metformin for obese type 2 DM patients.
27UKPDS 38Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 DM patients.Patients : 1148Multicenter, RCT median FU 8.4 yrs
28UKPDS 38 – con’t Findings: Lower mean BP in tight control group 24% reduced risks for developing any DM-related complications32% reduced risk of mortality44% reduced risk of stroke34% reduced risk of macrovascular disease37% reduced risk of microvascular disease56% reduction in heart failureNNT 10 yrs to prevent any complication=6NNT 10 yrs to prevent one DM-related death= 15
29UKPDS 39Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 DM patients1148 patients:758 – tight control of BP400 – captopril358 – atenolol
30UKPDS 39 – con’tResults:- 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
31UKPDS 40Cost-effectiveness of improved BP control in hypertensive type 2 DM patientsConclusion: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.
32Lipids StudiesThese are well-known studies and therefore will only be mentioned briefly and given as summary:Note that the outcome measures of all lipid studies are using relative risk of “coronary heart disease” because high serum lipid by itself is meaningless.
33Lipid Studies Secondary prevention studies: 1) 4S study 2) CARE study 3) LIPID study 4) VA-HITPrimary prevention studies:1) Helsinki heart study 2)WOSCOPS3) AFCAPS/TexCAPS 4) BMJ –meta-analysis
34Scandinavian Simvastatin Survival Study Lancet 1994;344:1383-89 4444 patients, age 35-70, all had ischaemic heart disease, randomised to placebo or Simvastatin 20mgT.Chol= mmol/LMedian FU of 5.4 yearsDecreased cardiac mortality by 42%, all-cause mortality by 30%NNT for one fatal MI = 25 over 6 years (14 for non-fatal MI)
35Cholesterol And Recurrent Events (CARE) NEJM 1996;335:1001-1009 4159 post-MI patients, aged 21-75, mean T.Chol = 5.4 mmol/L and LDL-C = 3.6mmol/LRandomised for Pravastatin 40mg or PlaceboFU for 5 yearsResults:LDL-C fell by 32% and MI by 25% in treatment groupNNT for fatal MI =91 over 5 yrsNNT for non-fatal MI = 38 over 5 yrs
36Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study – NEJM 1998;339:1349 9014 patients, ages years, median T.Chol 5.66 mmol/LRandomised to Pravastatin 40 mg or PlaceboMean FU for 6.1 yearsResults:LDL-C fell by 25%24% reduction in CHD mortality22% reduction in all-cause mortality
37VA-HIT Study (Veterans Affairs High-density lipoprotein cholesterol Intervention Trial) NEJM1999;341:First secondary prevention trial using Gemfibrozil (Lopid) with promising results2531 men with IHD, with mean HDL<1.0 and LDL>3.6mmol/L, TG 1.78mmol/L, Tchol 4.55mmol/LSubjected to Lopid 600mg bd or placeboResults:HDL was 6% higher, TG 31% lower, LDL-unchangedReduction of RR for major CHD was 22%
38Helsinki Heart Study NEJM 1987;317:1237 Primary prevention trial with gemfibrozil in middle-aged men with dyslipidaemia.4081 men with mean T.Chol 7.51 mmol/LRandomised to Lopid 600mg bd or placebo.Results:- 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)
39West of Scotland Coronary Prevention Study (WOSCOPS) NEJM 1995;333:1301-07 Primary prevention trial of 6595 middle-aged men (age 45-64), with mean cholesterol 7.06 mmol/L.Randomised (double-blinded) to Pravastatin 40mg daily or placebo, mean FU 4.9 years.Results:- 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%.
40Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS) JAMA 1998;279:1615 6605 patients aged 55-73, with normal or mildly elevated total or LDL cholesterol, low HDL, & no clinically CVD.Randomised (double-blinded) to Lovastatin 20-40mg daily, or placebo. Mean FU for 5.2 yearsResults:- LDL reduction 25%, HDL raised 6%- reduced incidence of MI (RR 0.6), Angina (RR 0.68), Coronary events (RR 0.75)
41BMJ Meta-analysis on Primary Prevention Drug treatments reduced the odds of a CHD event by 30% (95%CI ) but not the odds of all cause mortality (95%CI ) – even with statins.Concluded that treatment with lipid lowering drugs lasting 5-7 years reduces coronary heart disease events but not all-cause mortality.