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  • Lowest rates of BP control
  • Figure 2. Mean Blood Pressure, Measured while Patients Were Seated, in the Intention-to-Treat Population, According to Study Group.
  • Table 2. Main Fatal and Nonfatal End Points in the Intention-to-Treat Population.
  • Geri pres

    1. 1. Ahad Lodhi, M.D. PGY-2 Internal Medicine Dept of GeriatricsCrozer-Chester Medical Center
    2. 2. BP Classification SBP mmHg DBP mmHgNormal <120 and <80Prehypertension 120–139 or 80–89Stage 1 Hypertension 140–159 or 90–99Stage 2 Hypertension >160 or >100
    3. 3. The HYpertension in the Very Elderly Trial N. Beckett, R. Peters, A. Fletcher, C. Bulpitt on behalf of the HYVET committees and investigators N Engl J Med Volume 358(18):1887-1898 May 1, 2008
    4. 4. • In this study, patients 80 years of age or older with sustained systolic hypertension were randomly assigned to receive either the diuretic indapamide, with or without the angiotensin- converting-enzyme inhibitor perindopril, or matching placebos, for a target blood pressure of 150/80 mm Hg• Active treatment resulted in a nearly significant reduction of the risks of fatal or nonfatal stroke and death from cardiovascular causes and a significant reduction in the rates of death from stroke and death from any cause, suggesting that antihypertensive treatment in these persons may be beneficial
    5. 5. The Trial:International, multi-centre, randomised double-blind placebo controlledInclusion Criteria: Exclusion Criteria:Aged 80 or more, Standing SBP < 140mmHgSystolic BP; 160 -199mmHg Stroke in last 6 months+ diastolic BP; <110 mmHg, DementiaInformed consent Need daily nursing carePrimary Endpoint:All strokes (fatal and non-fatal)
    6. 6. Entry,Randomization, andFollow-upof Patientsin theHypertension in theVeryElderlyTrial
    7. 7. 4761 Entered into Placebo Run-in916 not randomised Placebo Active 1912 1933
    8. 8. Baseline data Placebo Active (n= 1912) (n= 1933) Age (years) 83.5 83.6 Female 60.3% 60.7% Blood Pressure: Sitting SBP (mmHg) 173.0 173.0 Sitting DBP (mmHg) 90.8 90.8 Orthostatic Hypotension‡ 8.8% 7.9% Isolated Systolic Hypertension 32.6% 32.3%‡ Fall in SBP ≥ 20mmHg and/or fall in DBP ≥ 10mmHg
    9. 9. Placebo Active (%) (%)Cardiovascular disease 12.0 11.5Known Hypertension 89.9 89.9Anti-hypertensive treatment 65.1 64.2Stroke 6.9 6.7Myocardial Infarction 3.2 3.1Heart Failure 2.9 2.9
    10. 10. Baseline data (Cardiovascular Risk factors) Placebo ActiveCurrent smoker 6.6% 6.4%Diabetes(Known DM/ DM treatment/glucose>11.1mmo/l) 6.9% 6.8%Total cholesterol (mmol/l) 5.3 5.3HDL Cholesterol (mmol/l) 1.35 1.35Serum Creatinine (μmol/l) 89.2 88.6Uric acid (µmol/l) 279 280Body Mass Index (kg/m2) 24.7 24.7
    11. 11. Mean Blood Pressure, Measured while Patients Were Seated, in the Intention-to-Treat Population, According to Study GroupBeckett NS et al. N Engl J Med 2008;358:1887-1898
    12. 12. 180 170 15 mmHg 160 150Blood Pressure (mmHg) 140 Placebo 130 120 Indapamide SR +/- Median follow-up 1.8 years I perindopril 110 100 6 mmHg 90 80 70 0 1 2 3 4 5 Follow-up (years)
    13. 13. Main Fatal and Nonfatal End Points in the Intention-to-Treat PopulationBeckett NS et al. N Engl J Med 2008;358:1887-1898
    14. 14. All strokeKaplan-Meier Estimates of the Rate of End Points,According to Study Group (30% reduction) P=0.055
    15. 15. Kaplan-Meier Estimates of the Rate of End Points,According to Study Group Total Mortality (21% reduction) P=0.019
    16. 16. Kaplan-Meier Estimates of the Rate of End Points,According to Study Group Fatal Stroke (39% reduction) P=0.046
    17. 17. Kaplan-Meier Estimates of the Rate of End Points, Heart Failure (64% reduction)According to Study Group P<0.0001
    18. 18. ITT – Summary HR 95% CIAll Stroke 0.70 (0.49, 1.01)Stroke Death 0.61 (0.38, 0.99)All cause 0.79 (0.65, 0.95)mortalityNCV/Unknown 0.81 (0.62, 1.06)deathCV Death 0.77 (0.60, 1.01)Cardiac Death 0.71 (0.42, 1.19)Heart Failure 0.36 (0.22, 0.58)CV events 0.66 (0.53, 0.82) 0.1 0.2 0.5 0 2
    19. 19. HR 95% CI PAll stroke - 34% 0.46 - 0.95 0.025Total mortality - 28% 0.59 - 0.88 0.001Fatal stroke - 45% 0.33 - 0.93 0.021Cardiovascular mortality -27% 0.55-0.97 0.029Heart failure -72% 0.17-0.48 <0.001Cardiovascular events - 37% 0.51-0.71 <0.001
    20. 20. •In 2 year cohort there were no significantdifferences between the groups with regard tochange in serum…. •Potassium •Uric acid •Glucose •Creatinine
    21. 21. Reported serious adverse events (after randomisation) 448 in the placebo group vs 358 in active (p=0.001)
    22. 22. Antihypertensive treatment based on indapamide (SR) 1.5mg (± perindopril) reduced stroke mortality and total mortality in a very elderly cohort.NNT (2 years) = 94 for stroke and 40 for mortalityLarge and significant benefit in reduction of heart failure events and for combined endpoint of cardiovascular eventsBenefits seen earlyTreatment regime employed was safe
    23. 23. Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitoror Calcium Channel Blocker vs DiureticThe Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
    24. 24. Objective: To determine whether treatment with a calcium channel blocker or anangiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease(CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic.Design: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT), a randomized, double-blind, active-controlled clinical trial con- ducted fromFebruary 1994 through March 2002.Setting and Participants: A total of 33 357 participants aged 55 years or older withhypertension and at least 1 other CHD risk factor from 623 North American centers
    25. 25. Primary outcome: Combined fatal CHD or non- fatal myocardial infarction, analyzed by intent-to-treatSecondary outcomes: ll- cause mortality, troke, ombined CHD (primary outcome, coronary revascularization, or angina with hospitalization) ombined CVD (combined CHD, stroke, treated angina without hospitalization,heart failure [HF],peripheral arterial disease
    26. 26. Mean follow-up was 4.9 yearsThe primary outcome occurred in 2956 participants, with no difference between treatmentsAll-cause mortality did not differ between groups.Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg,P=.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001)Amlodipine vs Chlorthalidone, secondary outcomes were similar except for a higher 6-yearrate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52)Lisinopril vs Chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); andHF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31)
    27. 27. Thiazide-type diuretics are superior in preventing 1or more major forms of CVD and are less expensive.They should be preferred for first-step antihyperten-sive therapy.
    28. 28. Objective. To assess the ability of antihypertensive drug treatment to reduce the risk ofnonfatal and fatal (total) stroke in isolated systolic hypertension.Design. Multicenter, randomized, double-blind, placebo-controlled.Setting. Community-based ambulatory population in tertiary care centers.Participants. 4736 persons (1.06%) from 447 921 screenes aged 60 years and above wererandomized (2365 to active treatment, 2371 to placebo).Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure wasless than 90 mm Hg.3161 were not receiving antihypertensive medication at initial contact, and 1575 were.The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77mm Hg. The mean age was 72 years, 57% were women, and 14% were black
    29. 29. Participants were stratified by clinical center and by antihypertensive medication status atinitial contact.step 1 of the trial:dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d.step 2: dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d.Main Outcome MeasuresPrimary. Nonfatal and fatal (total) strokeSecondary. Cardiovascular and coronary morbidity and mortality, all-cause mortality, andquality of life measures.
    30. 30. Average follow-up was 4.5 yearsThe 5-year average systolic blood pressure was 155mm Hg for the placebo group and143mm Hg for the active treatment group, and the 5-year average diastolic bloodpressure was 72 and 68mmHg, respectively.The 5-year incidence of total stroke was 5.2 per 100 participants for active treatmentand 8.2 per 100 for placeboThe relative risk by proportional hazards regression analysis was 0.64 (P=.0003).For the secondary end point of clinical nonfatal myocardial infarction plus coronarydeath, the relative risk was 0.73. Major cardiovascular events were reduced (relativerisk, 0.68). For deaths from all causes, the relative risk was 0.87.
    31. 31. In persons aged 60 years and over with isolated systolichypertension, antihypertensive stepped-care drug treatmentwith low-dose chlorthalidone as 1 medication reduced theincidence of total stroke 36%, with 5-year absolute benefit of 30events per 1000 participantsMajor cardiovascular events were reduced, with 5-year absolutebenefit of 55 events per 1000

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