2 Mrs Khan 56 BP 158/99 BMI 32 Total cholesterol 5.4 (HDL 0.8) HbA1c 43 She has been promising to do more exercise and eat more healthily for the last 2 years but her weight has gone up. She gets side effects with most meds and isn t keen to take any tablets. She feels fine thank you
7 Measuring Blood Pressure Clinic (Doctor) manual vs automated Clinic (non-doctor) Home readings (1week) Ambulatory (24hrs) Lying/sitting/standing Size of cuff Position of arm Which arm?
8 Causes of Hypertension Unknown or essential Hyperaldosteronism 5-10% Renal disease Cushings syndrome Thyroid disease Phaechromocytoma %
9 The Lancet , DOI: ( /S (14) ) Copyright 2014 Rapsomaniki et al. Open Access article distributed under the terms of CC BY Terms and Conditions Figure 1 Is high blood pressure bad for you? HR per 20/10mm Hg
10 Figure 5 The Lancet , DOI: ( /S (14) ) Copyright 2014 Rapsomaniki et al. Open Access article distributed under the terms of CC BY Terms and Conditions
11 What systolic blood pressure is bad for you? It depends on how you look at it
13 What does weight loss achieve? Evidence is of poor quality 4kg weight loss overall produced 4.5/3.2 mm Hg reduction No data on mortality or morbidity
14 moderate reduction (3gram/day) may achieve up to 3-5/ mmhg reduction No data on morbidity/mortality Switch to low alcohol beer resulted in a 3/1.5 mm Hg reduction No data on morbidity/mortality
15 Dietary Approaches to Stop Hypertension 1997 NEJM 459 adults av. Age 44 BP 132/85 Food prepared in lab kitchen Control Fruit and Vegetables Diet Combination Diet
20 What about exercise?
22 16 MAs, 305 RCTs with participants
26 Perspectives on Drugs to lower mild BP
27 Use of blood pressure lowering drugs in the prevention of cardiovascular disease: metaanalysis of 147 randomised trials in the context of expectations from prospective epidemiological studies M R Law, professor of epidemiology J K Morris, professor of medical statistics N J Wald, professor of environmental and preventive medicine BMJ 2009;338:b1665
28 Cochrane 2012
31 What about different medications?
32 The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT study overview Double-blind, randomized trial to determine whether the occurrence of fatal CHD or nonfatal MI is lower for high-risk hypertensive patients treated with newer agents (amlodipine, lisinopril, or doxazosin) compared with a diuretic (chlorthalidone) Cohort 42,418 patients ( 55 years old) from 623 sites in North America Stage 1 or 2 hypertension 1 additional risk factor for CHD Comparisons between chlorthalidone and amlodipine and chlorthalidone and lisinopril have been reported together, excluding the doxazosin arm (n=9,062), which was terminated early CHD=coronary heart disease; MI=myocardial infarction ALLHAT Research Group. JAMA. 2002;288: org
33 Doxazosin n=9,062 ALLHAT Study Design Discontinued early at 3.3 yrs Randomized n=42,418 YEAR 1 Chlorthalidone n=15,255 n=13,854 2,235 (16.1%) stopped drug Amlodipin e n=9,048 n=8,215 1,357 (16.5%) stopped drug Lisinopril n=9,054 n=8,158 1,842 (22.6%) stopped drug YEAR 5 n=6,210 1,873 (30.2%) stopped drug n=3,769 1,052 (27.9%) stopped drug n=3,605 1,399 (38.8%) stopped drug n=9, (2.4%) lost to followup 58 (0.6%) refused follow-up ntent-to- Treat Analysis n=15, (2.2%) lost to followup 80 (0.5%) refused follow-up n=9, (2.2%) lost to follow-up 58 (0.6%) refused follow-up ALLHAT Research Group. JAMA. 2002;288: org
35 ALLHAT Baseline Characteristics Chlorthalidon e n=15,255 systoli c diastoli c Amlodipine n=9,048 systolic diastoli c Lisinopril n=9,054 systoli c diastoli c Mean BP (mmhg) Treated (90%) Untreated (10%) Mean age (yrs) Black (%) Women (%) Current smoking (%) History of CHD (%) BP=blood pressure CHD=coronary heart disease Type 2 diabetes (%) ALLHAT Research Group. JAMA. 2002;288: org
36 Systolic BP (mmhg) Diastolic BP (mmhg) ALLHAT Mean Systolic and Diastolic Blood Pressure During Follow-up Chlorthalidone Chlorthalidone 150 Amlodipine Lisinopril 90 Amlodipine Lisinopril Compared to chlorthalidone: SBP significantly higher in amlodipine (~1 mmhg) and lisinopril (~2 mmhg) groups Compared to chlorthalidone: DBP significantly lower in amlodipine group (~1 mmhg) Follow-up, yrs SBP=systolic blood pressure ALLHAT Research Group. JAMA. 2002;288: pressure Copyright 2002, American Medical Association. DBP=diastolic blood org
37 % Patients with BP <140/90 mmhg ALLHAT BP Controlled to <140/90 mmhg Chlorthalidone * * Amlodipine Lisinopril Baseline Year 1 Year 2 Year 3 Year 4 Year 5 *P<0.001 for amlodipine vs chlorthalidone P<0.001 for lisinopril vs chlorthalidone ALLHAT Research Group. JAMA. 2002;288: org
38 Patients (%) ALLHAT Treatment and Blood Pressure Control Drug 2 Drugs 3 Drugs Average # of drugs 0 6 mos 1 yr 3 yr 5 yr Blood pressure controlled <140/90 mmhg 49.8% 55.2% 62.3% 65.6% Cushman WC, et al. J Clin Hypertens. 2002;4: org 0
39 Cumulative Fatal CHD and Nonfatal MI event rate (%) ALLHAT Primary Outcome by Treatment Group Chlorthalidone Amlodipine Lisinopril 8 4 No. at Risk Chlorthalidone Amlodipine Lisinopril Time to event, yrs ALLHAT Research Group. JAMA. 2002;288: Copyright 2002, American Medical Association org
40 ALLHAT CHD Death and Nonfatal MI TOTAL Age <65 Age 65 Men Women Black Nonblack Diabetic Nondiabeti c Relative Risk Favors Favors Relative Risk Favors Favors (95% CI) amlodipine chlorthalidone (95% CI) lisinopril chlorthalidone 0.98 ( ) 0.99 ( ) 0.97 ( ) 0.98 ( ) 0.99 ( ) 1.01 ( ) 0.97 ( ) 0.99 ( ) 0.97 ( ) 0.99 ( ) 0.95 ( ) 1.01 ( ) 0.94 ( ) 1.06 ( ) 1.10 ( ) 0.94 ( ) 1.00 ( ) 0.99 ( ) ALLHAT Research Group. JAMA. 2002;288: Copyright 2002, American Medical Association. org
41 TOTAL Age <65 Age 65 Men Women Black Nonblack Diabetic Nondiabeti c ALLHAT All-Cause Mortality Relative Risk Favors Favors Relative Risk Favors Favors (95% CI) amlodipine chlorthalidone (95% CI) lisinopril chlorthalidone 0.96 ( ) 0.96 ( ) 0.96 ( ) 0.95 ( ) 0.96 ( ) 0.97 ( ) 0.94 ( ) 0.96 ( ) 0.95 ( ) 1.00 ( ) 0.93 ( ) 1.03 ( ) 0.99 ( ) 1.02 ( ) 1.06 ( ) 0.97 ( ) 1.02 ( ) 1.00 ( ) ALLHAT Research Group. JAMA. 2002;288: Copyright 2002, American Medical Association. org
42 TOTAL Age <65 Age 65 Men Women Black Nonblack Diabetic Nondiabeti c ALLHAT Combined CV Disease Relative Risk Favors Favors Relative Risk Favors Favors (95% CI) amlodipine chlorthalidone (95% CI) lisinopril chlorthalidone 1.04 ( ) 1.03 ( ) 1.05 ( ) 1.04 ( ) 1.04 ( ) 1.06 ( ) 1.04 ( ) 1.06 ( ) 1.02 ( ) 1.10 ( ) 1.05 ( ) 1.13 ( ) 1.08 ( ) 1.12 ( ) 1.19 ( ) 1.06 ( ) 1.08 ( ) 1.12 ( ) ALLHAT Research Group. JAMA. 2002;288: Copyright 2002, American Medical Association. org
43 Cumulative event rate (%) ALLHAT Stroke by Treatment Group Chlorthalidone Amlodipine Lisinopril 4 2 No. at Risk Chlorthalidone Amlodipine Lisinopril Time to event, yrs ALLHAT Research Group. JAMA. 2002;288: Copyright 2002, American Medical Association org
44 ALLHAT Stroke Relative Risk Favors Favors Relative Risk (95% CI) amlodipine chlorthalidone (95% CI) Favors Favors lisinopril chlorthalidone TOTAL Age <65 Age 65 Men Women Black Nonblack Diabetic Nondiabeti c 0.93 ( ) 0.93 ( ) 0.93 ( ) 1.00 ( ) 0.84 ( ) 0.93 ( ) 0.93 ( ) 0.90 ( ) 0.96 ( ) 1.15 ( ) 1.21 ( ) 1.13 ( ) 1.10 ( ) 1.22 ( ) 1.40 ( ) 1.00 ( ) 1.07 ( ) 1.23 ( ) ALLHAT Research Group. JAMA. 2002;288: Copyright 2002, American Medical Association. org
45 Cumulative event rate (%) ALLHAT Heart Failure by Treatment Group Chlorthalidone Amlodipine Lisinopril P<0.001 for chlorthalidone vs amlodipine and chlorthalidone vs lisinopril 6 3 No. at Risk Chlorthalidone Amlodipine Lisinopril Time to event, yrs ALLHAT Research Group. JAMA. 2002;288: Copyright 2002, American Medical Association org
46 TOTAL Age <65 Age 65 Men Women Black Nonblack Diabetic Nondiabeti c ALLHAT Heart Failure Relative Risk Favors Favors Relative Risk Favors Favors (95% CI) amlodipine chlorthalidone (95% CI) lisinopril chlorthalidone 1.38 ( ) 1.51 ( ) 1.33 ( ) 1.41 ( ) 1.33 ( ) 1.47 ( ) 1.33 ( ) 1.42 ( ) 1.33 ( ) 1.20 ( ) 1.23 ( ) 1.20 ( ) 1.19 ( ) 1.23 ( ) 1.32 ( ) 1.15 ( ) 1.22 ( ) 1.20 ( ) ALLHAT Research Group. JAMA. 2002;288: Copyright 2002, American Medical Association. org
47 ALLHAT Conclusions Better control of systolic BP was achieved with chlorthalidone than with amlodipine or lisinopril There were no differences in risk for CHD death/nonfatal MI between chlorthalidone and amlodipine or lisinopril In secondary endpoints, chlorthalidone was associated with lower risk for stroke, combined CVD, and HF compared with lisinopril HF compared with amlodipine MI=myocardial infarction CHD=coronary heart disease HF=heart failure ALLHAT Research Group. JAMA. 2002;288: org
48 A randomised controlled trial of the prevention of CHD and other vascular events by BP and cholesterol lowering in a factorial study design B.Dahlof (Co-chair), P.Sever (Co-chair), N. Poulter (Secretary) H. Wedel (Statistician), G. Beevers, M. Caulfield, R. Collins S. Kjeldsen, A. Kristinsson, J. Mehlsen, G. McInnes, M. Nieminen E. O Brien, J. Östergren, on behalf of the ASCOT Investigators
49 ASCOT- BPLA Primary Objective To compare the effect on non-fatal myocardial infarction (MI) and fatal CHD of the standard antihypertensive regimen ( -blocker ± diuretic) with a more contemporary regimen (CCB ± ACE inhibitor)
51 Patient inclusion criteria Screening and baseline BP 160/100 mm Hg untreated 140/90 mm Hg following treatment with 1 or more drugs Age years No previous MI or current clinical CHD 3 or more CV risk factors
52 Treatment algorithm to BP targets < 140/90 mm Hg or < 130/80 mm Hg in patients with diabetes amlodipine 5-10 mg add perindopril 4-8 mg atenolol mg add bendroflumethiazide-k mg add doxazosin GITS 4-8 mg add additional drugs, eg, moxonidine/spironolactone
53 Baseline characteristics amlodipine perindopril atenolol thiazide Demographics and clinical characteristics n = 9639 n = 9618 Woman 2258 (23.4%) 2257 (23.5%) White 9187 (95.3%) 9170 (95.3%) Current smoker 3168 (32.9%) 3110 (32.3%) Age (years) 63.0 (8.5) 63.0 (8.5) SBP (mm Hg) (18.1) (18.0) DBP (mm Hg) 94.8 (10.4) 94.5 (10.4) Heart rate (bpm) 71.9 (12.7) 71.8 (12.6) BMI (kg/m 2 ) 28.7 (4.6) 28.7 (4.5) Drug therapy Previous antihypertensive treatments (19.1%) 1825 (19.0%) (44.4%) 4283 (44.5%) (36.5%) 3510 (36.5%) Lipid-lowering therapy 1046 (10.9%) 1004 (10.4%) Aspirin 1851 (19.2%) 1837 (19.1%) Values are number of patients, (%) or mean (SD)
54 mm Hg Systolic and diastolic blood pressure SBP Mean difference 2.7 atenolol thiazide amlodipine perindopril DBP Mean difference Baseline Time (years) Last visit
55 Summary of all end points Primary Non-fatal MI (incl silent) + fatal CHD Secondary Non-fatal MI (exc. Silent) +fatal CHD Total coronary end point Total CV event and procedures All-cause mortality Cardiovascular mortality Fatal and non-fatal stroke Fatal and non-fatal heart failure Tertiary Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Life-threatening arrhythmias New-onset diabetes mellitus New-onset renal impairment Amlodipine perindopril better Atenolol thiazide better Post hoc Primary end point + coronary revasc procs The area of the blue square is proportional to the amount of statistical information Unadjusted Hazard ratio (95% CI) 0.90 ( ) 0.87 ( ) 0.87 ( ) 0.84 ( ) 0.89 ( ) 0.76 ( ) 0.77 ( ) 0.84 ( ) 1.27 ( ) 0.68 ( ) 0.98 ( ) 0.65 ( ) 1.07 ( ) 0.70 ( ) 0.85 ( ) 0.86 ( )
56 Variables which differed significantly (baseline - final visit) between treatment regimens Mean differences (Amlodipine perindopril - Atenolol thiazide) Changes baseline to final visit p-value Systolic BP (mm Hg) < Diastolic BP (mm Hg) < Heart rate (bpm) < Weight (kg) < HDL-cholesterol (mmol/l) 0.11 < Triglycerides (mmol/l) < Glucose (mmol/l) < Creatinine (µmol/l) < Potassium (mmol/l) 0.05 <0.0001
57 Impact on the treatment effect on coronary events after adjustment for BP and all variables that differed Hazard ratio 95% CI Unadjusted SBP SBP + covariates SBP + DBP + covariates MBP** + covariates PP + covariates Amlodipine perindopril better Atenolol thiazide better p-value Hazard ratio ** MBP = (SBP+DBP)/2
58 Impact on the treatment effect on stroke events after adjustment for BP and all variables that differed Hazard Hazard ratio ratio 95% CI 95% CI Unadjusted Mean BP SBP + covariates SBP + DBP + covariates MBP** + covariates PP + covariates Amlodipine perindopril better Atenolol thiazide better p-value Hazard ratio ** MBP = (SBP+DBP)/2
59 What about B-blockers?
61 What about the Elderly?
62 Systolic Hypertension in the Elderly JAMA 1991 Randomized, double-blind, placebo controlled 4736 people aged 60yrs+ BP /<90 Average BP 170/77, average age 72 Step 1 Chlorthalidone 12.5mg or placebo Step 2 Atenolol 25mg/placebo Atenolol 50mg/placebo
63 SHEP 1991 Follow up 4.5yrs Average BP 143/68 treatment group, 155/72 placebo 5.2% total stroke (treatment) vs 8.2% (placebo) 3% absolute risk reduction Coronary death and non fatal MI RR 0.73 All cause mortality RR 0.87
64 Indapamide 1.5mg MR then Perindopril 2mg/4mg
65 HYVET 2008
66 HYVET 2008
67 HYVET 2008
68 What about Diabetics?
71 Hypertension Optimal Treatment
72 HOT trial Non diabetics
73 HOT trial Diabetics
81 Randomised open label study 9361 average BP 140/78 at start Intensive 120/- or Standard 140/- Stopped early after 3.2yrs
85 Conclusions? How I see it anyway Good evidence for lowering BP in stage 2 BP reducing mortality and morbidity (SHEP) Some evidence for tighter targets for diabetic patients reducing cardiovascular mortality but not total mortality but from starting BP (HOT) Some emerging evidence for tighter BP targets in one recent study (SPRINT). Little difference between different drug groups (ASCOT, ALLHAT)
86 Conclusions 2 Medications for mild hypertension not demonstrated (apart from SPRINT) Tighter BP targets in CKD is based on observation of association not RCTs Some evidence that ACEI less good in black ethnic groups
88 High Blood Pressure: Background Major risk factor for stroke, myocardial infarction, heart failure, chronic kidney disease, cognitive decline and premature death. Untreated hypertension can cause vascular and renal damage leading to a treatment-resistant state. Each 2 mmhg rise in systolic blood pressure associated with increased risk of mortality: 7% from heart disease 10% from stroke.
89 Epidemiology Hypertension is common in the UK population. Prevalence influenced by age and lifestyle factors. 25% of the adult population in the UK have hypertension. 50% of those over 60 years have hypertension. With an ageing population, the prevalence of hypertension and requirement for treatment will continue to increase.
90 Definitions Stage 1 hypertension: Clinic blood pressure (BP) is 140/90 mmhg or higher and ABPM or HBPM average is 135/85 mmhg or higher. Stage 2 hypertension: Clinic BP 160/100 mmhg is or higher and ABPM or HBPM daytime average is 150/95 mmhg or higher. Severe hypertension: Clinic BP is 180 mmhg or higher or Clinic diastolic BP is 110 mmhg or higher.
91 Diagnosis (1) If the clinic blood pressure is 140/90 mmhg or higher, offer ambulatory blood pressure monitoring (ABPM) to confirm the diagnosis of hypertension.
92 Diagnosis (2) When using the following to confirm diagnosis, ensure: ABPM: at least two measurements per hour during the person s usual waking hours, average of at least 14 measurements to confirm diagnosis HBPM: two consecutive seated measurements, at least 1 minute apart blood pressure is recorded twice a day for at least 4 days and preferably for a week measurements on the first day are discarded average value of all remaining is used.
93 Initiating drug treatment Offer antihypertensive drug treatment to people: who have stage 1 hypertension, are aged under 80 and meet identified criteria who have stage 2 hypertension at any age. If aged under 40 with stage 1 hypertension and without evidence of target organ damage, cardiovascular disease, renal disease or diabetes, consider: specialist evaluation of secondary causes of hypertension further assessment of potential target organ damage.
94 Monitoring drug treatment (1) Use clinic blood pressure measurements to monitor response to treatment. Aim for target blood pressure below: 140/90 mmhg in people aged under /90 mmhg in people aged 80 and over
95 Type 2 Diabetes BP targets
96 Monitoring drug treatment (2) For people identified as having a white-coat effect consider ABPM or HBPM as an adjunct to clinic blood pressure measurements to monitor response to treatment. Aim for ABPM/HBPM target average of: below 135/85 mmhg in people aged under 80 below 145/85 mmhg in people aged 80 and over. White-coat effect: a discrepancy of more than 20/10 mmhg between clinic and average daytime ABPM or average HBPM blood pressure measurements at the time of diagnosis.
97 CBPM 140/90 mmhg & ABPM/HBPM 135/85 mmhg Stage 1 hypertension CBPM 160/100 mmhg & ABPM/HBPM 150/95 mmhg Stage 2 hypertension Care pathway If target organ damage present or 10-year cardiovascular risk > 20% Offer antihypertensive drug treatment If younger than 40 years Consider specialist referral Offer lifestyle interventions Offer patient education and interventions to support adherence to treatment Offer annual review of care to monitor blood pressure, provide support and discuss lifestyle, symptoms and medication
98 Aged under 55 years A Aged over 55 years or black person of African or Caribbean family origin of any age C 2 Step 1 Summary of antihypertensive drug treatment A + C 2 A + C + D Resistant hypertension A + C + D + consider further diuretic 3, 4 or alpha- or beta-blocker 5 Consider seeking expert advice Step 2 Step 3 Step 4 Key A ACE inhibitor or low-cost angiotensin II receptor blocker (ARB) 1 C Calcium-channel blocker (CCB) D Thiazide-like diuretic See slide notes for details of footnotes 1-5
99 Choosing antihypertensive drug treatment Offer people aged 80 and over the same antihypertensive drug treatment as people aged over 55, taking into account any comorbidities. Drug treatment
100 * See notes Measuring blood pressure: updated recommendations Standardise the environment and provide a relaxed, temperate setting with the person quiet and seated. When using an automated device: palpate the radial or brachial pulse before measuring blood pressure. If pulse if irregular measure blood pressure manually ensure that the device is validated* and an appropriate cuff size for the person s arm is used.
101 Assessing cardiovascular risk and target organ damage: updated recommendations Use a formal estimation of cardiovascular risk to discuss prognosis and healthcare options with people with hypertension. For all people with hypertension offer to: test urine for presence of protein take blood to measure glucose, electrolytes, creatinine, estimated glomerular filtration rate and cholesterol examine fundi for hypertensive retinopathy arrange a 12-lead ECG.
102 Additional recommendations Lifestyle interventions Offer guidance and advice about: diet (including sodium and caffeine intake) and exercise alcohol consumption smoking. Patient education and adherence Provide: information about benefits of drugs and side effects details of patient organisations an annual review of care.
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