primaire cardiovasculaire preventie op SCORE voor ouderen Effect van primaire cardiovasculaire preventie op SCORE voor ouderen Emma van Bussel, aiotho Juni 2017 10min + 5min vragen/discussie

Disclosure belangen NHG spreker (Potentiële) belangenverstrengeling Geen Voor bijeenkomst mogelijk relevante relaties met bedrijven Sponsoring of onderzoeksgeld Honorarium of andere (financiële) vergoeding Aandeelhouder Andere relatie, namelijk …

Introductie Driver et al. BMJ 2008

Introductie Primaire CV preventie is effectief1 Onduidelijk of dit ook geldt voor ouderen2 Multicomponente CV preventie onder 3526 ouderen in preDIVA3: neutraal effect op HVZ Mogelijke verklaring: relatief korte follow-up van 5 jaar Sinds 1980 CVD mortality langzaam afgenomen, maar CVD-morbidity is juist toegenomen in Europese landen. Mn effectief bij mensen van middelbare leeftijd metgemiddeld tot hoog risicoprofiel 2. Omdat atherosclerose al lange tijd op heeft kunnen bouwen, en risicoprofiel verbeteren deze opgebouwde schade mogelijk niet meer teniet kan doen. Toch ook studies die wel effect laten zien. preDIVA, trial onder 3500 ouderen in algemene populatie, naar effect van multicomponente cardiovascuilaire preventie 1. Piepoli et al. Eur Heart J 2016; 2. de Rezende et al. BMC Public Health 2014; 3. Moll van Charante et al. Lancet 2016

Onderzoeksvraag Heeft multicomponente primaire cardiovasculaire preventie effect op intermediaire CV uitkomsten bij ouderen? Uitkomstmaten SCORE-OP Index voor: leeftijd, geslacht, roken, bloeddruk, diabetes, totaal- en HDL-cholesterol 2. Individuele risicofactoren SCORE-OP:10y risico op ziekte en sterfte agv HVZ

preDIVA 3526 baseline assessment no CVD at baseline: 2254 (64%) 116 practices 7772 subjects 70-78 years 14% not eligible 46,7% no informed consent 3526 baseline assessment no CVD at baseline: 2254 (64%) component intervention blood pressure lifestyle, medication smoking help with cessation physical activity counseling bodyweight BMI>25: counseling, >30: dietician cholesterol TC >5: statin glucose > 6.1 mmol/l -> treatment standard care vascular care For the preDIVA trial all persons aged 70-78 years without prevalent dementia or a limited life expectancy were invited. Over 50% of eligible persons participated in the study resulting in a sample size of over 3500 persons. With this sample size we had 80% power to detect a 33% risk reduction of dementia. After baseline assessment the whole practice was randomised into xx; which comprised of 4-monthly visits to a NP addressing all vascular risk factors using medical and non-medical interventions. Primary outcome was all-cause dementia during 6-year follow-up. And secondary outcomes were … As you can see here the recruitment phase took 3 years. So by the time the first participants were in the study for 6 years they were allowed to continue in the study up to a maximum of 8 years which increased the power of our study. 4-monthly visit 2 year 4 year 6/ 6+ year Richard et al. Alz Dis Ass Disord 2009

Methode - statistiek Intention to treat SCORE-OP en Individuele risicofactoren Adjusted mean difference middels linear mixed-effects models gecorrigeerd voor clustering

Resultaten Baseline characteristics: demographics Intervention (n=792)   Intervention (n=792) Control (n=709) Age in year, mean (SD) 74.1 (2.4) 74.1 (2.5) Male, no. (%) 297 (38%) 275 (39%) Educational level no. (%) <7 years 7-12 years >12 years 165 (21%) 519 (66%) 108 (14%) 161 (23%) 461 (65%) 87 (12%) Caucasian, no.(%) 755 (95%) 688 (97%) More participants were randomised to the intervention group which is a consequence of the cluster-randomisation algorithm we applied. Deze groep oha gezonder dan de gehele preDIVA populatie, want primaire preventie groep.

Resultaten Baseline characteristics: CVD risk factors Intervention   Intervention (792) Control (709) SBP in mmHg, mean (SD) 156.0 (21.0) 154.9 (20.1) DBP in mmHg, mean (SD) 81.7 (10.8) 82.3 (10.5) Total cholesterol in mmol/L, mean (SD) 5.44 (0.97) 5.58 (1.09) HDL cholesterol in mmol/L, mean (SD) 1.56 (0.41) 1.56 (0.42) Type 2 diabetes, no. (%) 145 (18%) 98 (14%) Current smoking, no. (%) 82 (12%) 83 (10%) Wat opvalt: verschil tussen interventie en controle groep bij SBP en DM. ws door cluster randomisatie

Resultaten: effect op SCORE-OP Effect on SCORE-OP Outcome Mean baseline risk, % (SD)   Intervention Control 10-year CVD-mortality risk 14.0 (7.7) 13.9 (7.9)

Resultaten: effect op SCORE-OP Effect on SCORE-OP Outcome Mean baseline risk, % (SD) Mean risk during study, % (SD)   Intervention Control 10-year CVD-mortality risk 14.0 (7.7) 13.9 (7.9) 23.9 (13.7) 25.0 (14.1)

Resultaten: effect op SCORE-OP Effect on SCORE-OP Outcome Mean baseline risk, % (SD) Mean risk during study, % (SD) Adjusted mean difference (95%CI)   Intervention Control 10-year CVD-mortality risk 14.0 (7.7) 13.9 (7.9) 23.9 (13.7) 25.0 (14.1) -0.60 (-1.20 to 0.01)

Resultaten: effect op risicofactoren Adjusted mean difference (95%CI) for individual risk factors of SCORE-OP Outcome Mean at baseline Mean during study Adjusted mean difference (95%CI) Intervention Control SBP mmHg 156 (21) 155 (20) 149 (19) 151 (21) -2.39 (-3.90 to -0.87)  Total cholesterol mmol/L 5.44 (0.97) 5.58 (1.09) 5.24 (1.06) 5.35 (1.10) -0.03 (-0.12 to 0.02) HDL-cholesterol mmol/L 1.56 (0.41) 1.56 (0.42) 1.53 (0.41) 1.54 (0.44) -0.00 (-0.02 to 0.02) Smoking status 10.4 (30.5) 11.7 (32.2) 7.1 (25.6) 9.6 (29.4) -1.85 (-0.35 to -3.36) Type 2 diabetes mellitus 18.3 (38.7) 13.8 (34.5) 20.0 (40.0) 16.3 (36.9) -0.73 (-2.19 to 0.74)  For smoking status and type 2 diabetes mellitus figures reflect the percentage within the population, the adjusted mean difference reflects the absolute difference in this percentage between study groups.

Resultaten: effect op risicofactoren

Samenvatting Geen effect op SCORE-OP Intermediaire risicofactoren: 2,4 mmHg daling op systolische bloeddruk 1,9% daling in roken

Discussie Multifactoriele interventie onder ouderen, breed generaliseerbaar, met een relatief lange follow-up Mogelijke bias Drop-out rate van 39% maar geen verschil in joint model analyse Hawthorne effect Klein contrast tussen studie-armen Studies onder ouderen geven aanwijzingen voor ‘reverse epidemiology’ Traditionele associatie tussen risicofactoren en HVZ verdwijnen of veranderen

Conclusie In deze studie: effect op bloeddruk en roken, maar niet op SCORE-OP Door Hawthorne effect en klein contrast type II fout niet uit te sluiten Toekomstig onderzoek naar primaire preventie onder ouderen Landen met minder goede CV standaard zorg Risicogroep selectie

In samenwerking met Dr. W.B. Busschers PreDIVA studiegroep (AMC) Dr. E. Richard Prof. dr. W.A. van Gool Dr. E.P. Moll van Charante Dr. M.P. Hoevenaar-Blom Statistisch en specialistisch advies Dr. W.B. Busschers Prof. dr. R.J.G. Peters

Vragen?

Resultaten: effect op HVZ Hazard ratios for relative risk of CVD incidence and all-cause mortality in the intervention compared to the control group, adjusted for clustering. Outcome Intervention group n=1039 Control group n=1215 Hazard ratio (95%CI) Total CVD 75/790 (9.5%) 65/715 (9.1%) 0.99 (0.71 to 1.38) CVD mortality 21/1074 (2.0%) 21/941 (2.2%) 0.87 (0.46 to 1.65) CVD morbidity 55/821 (6.7%) 45/724 (6.2%) 1.01 (0.68 to 1.50) CHD morbidity 42/975 (4.3%) 32/870 (3.7%) 1.08 (0.68 to 1.71) Non-CHD morbidity 15/818 (1.8%) 14/721 (1.9%) 0.93 (0.45 to 1.93) All-cause mortality 158/1211 (13.0%) 118/1038 (11.4%) 1.15 (0.88 to 1.49) CVD: cardiovascular disease, CHD: coronary heart disease. Total CVD: CVD morbidity and mortality, HR: Hazard ratio 1. CVD mortality + CVD morbidity 2. mortality from myocardial infarction or stroke 3. non-fatal events of myocardial infarction or stroke 4. non-fatal events of myocardial infarction 5. non-fatal events of stroke 6. A sensitivity analysis was conducted here , with CVD-mortality defined as definite CVD-mortality, uncertain or unknown cause of mortality 

Resultaten: subgroep analyses Subgroup analysis   SCORE-OP: 10 y risk of CVD mortality Mean baseline risk, % (SD) Mean risk during study, % (SD) Adjusted mean difference (95%CI) Difference in treatment differences (95%CI) Intervention group Control group Gender   Men (n=572) 17.0 (7.8) 17.6 (8.3) 26.6 (13.5) 29.2 (14.2) -0.70 (-1.64 to 0.23) 0.11 (-1.05 to 1.27) Women (n=929) 12.2 (7.0) 11.6 6.7) 22.3 (13.5) 22.4 (13.4) -0.59 (-1.33 to 0.15) - Indication for drug treatment Indication (n=874) 17.6 (7.2) 17.8 (7.9) 28.7 (14.1) 30.1 (14.5) -0.72 (-1.51 to 0.06) 0.30 (-0.87 to 1.47) No indication (n=627) 8.8 (4.8) 8.7 (4.0) 17.3 (9.9) 18.4 (10.5) -0.43 (-1.33 to 0.48) Type 2 diabetes mellitus No T2DM (n=1258) 12.2 (6.1) 12.4 (6.2) 21.0 (11.2) 23.2 (12.9) -1.10 (-1.76 to -0.45) 2.64 (1.07 to 4.21) T2DM (n=243) 21.9 (9.0) 23.4 (10.4)  36.7 (16.2) 36.2 (15.9) +1.54 (0.08 to 2.99)

Figure S2. Mean percentage of targets reached per individual for SBP, LDL-cholesterol, smoking status and TC/HDL ratio, during study.   For every biannual measurement round, the mean percentage of targets reached per individual is given, for the variables SBP, LDL, TC/HDL and smoking status. BL: Baseline; 2: measurement at 2 year follow-up; 4: measurement at 4 year follow-up; 6+: measurement at last measurement round (follow-up between 6 and 8 years) Error bars represent 95% confidence intervals of (unadjusted) one-sample t-tests per study visit per study arm.