A survey study across GPs from 30 countries Influence of patient characteristics on GPs advice on stopping statins in oldest-old A survey study across GPs from 30 countries Milly van der Ploeg, Sven Streit, Rosalinde Poortvliet & Jacobijn Gussekloo Public Health en Eerstelijnsgeneeskunde Lumc, Leiden

Disclosure belangen NHG spreker (Potentiële) belangenverstrengeling None Voor bijeenkomst mogelijk relevante relaties met bedrijven Sponsoring of onderzoeksgeld Honorarium of andere (financiële) vergoeding Aandeelhouder Andere relatie, namelijk …

Collaborators Thank you: Nettie Blankenstein, Erna Beers, Arthur Bohnen, Daiana Bonfim, Huib Burger, Robert Burman, Tuz Canan, Claire Collins , Fabio Gazelato de Mello Franco , Margot de Waal, Biljana Gerasimovska-Kitanovska, Sandra Gintere, Raquel Gomez Bravo, Kathryn Hoffmann, Claudia Iftode, Kasper Johansen, Tuomas Koskela, Donata Kurpas, Hubert Maisonneuve, Christan Mallen, Christoph Merlo, Yolanda Müller , Christiane Muth, Martin Sattler, Sanda K Peštić, Ferdinando Petrazzuoli, Nicolas Rodondi, Thomas Rosemann , Tjard Schermer, Marija Petek Šter, Zuzana Švadlenková, Athina Tatsioni, Hans Thulesius, Victoria Tkachenko , Péter Torzsa, Rosy Tsopra, Bert Vaes, Marjan van den Akker , Rita Viegas, Shlomo Vinker, Katharine Wallis, Andreas Zeller

Background I Statins are widely used in old age, one of the drivers of polypharmacy With increasing age, accumulation of disease or in case of life limiting illness the risk-to –benefit ration might shift towards favoring stopping Current clinical practice guidelines offer little guidance for stopping Some GPs follow guidelines while others base treatment decisions on other factors like co-morbidity, frailty and life expectancy1 1Jansen et al. General practitioners Decision Making about Primary Prevention of Cardiovascular Disease in Older Adults: A Qualitative study. PloseOne, 2017. 12 (1): pe0170228 NHG Wetenschapsdag Juni 2018

Research questions To what extent do patient related characteristics (frailty, statin related side effects, history of CVD or limited life expectancy) influence GPs advice to stop statins in oldest old? Is there treatment variation across countries? NHG Wetenschapsdag Juni 2018

Methods I/IV- Summary Build a online questionnaire Contacted the study coordinators from the 29 countries participating in ATTENTIVE + 1 new coordinator for Belgium Study coordinators distributed the survey across their networks (median 150 GPs, range 15-11,00) Inclusion criteria: 1) confirm to be a practicing GP, 2) answer at least 1 question Study coordinators translated the survey in their own language (21) NHG Wetenschapsdag Juni 2018

Methods II/IV- The questionnaire Basic characteristics gender, years of experience, location of practice, estimated proportion of patients > 80 years, guideline compliance Case vignettes 8 case descriptions of patients > 80 years of unspecified gender who consulted the GP for a routine control. Varying in: 1) Frailty 2 2) Statin related side effects 3) History of cardiovascular disease 4) Life expectancy < 1 year 2 Fried criteria frail, this will be defined as patients with at least 2 of the following criteria: unintentional weight loss, exhaustion, low level of activity, muscle weakness and slow gait speed. NHG Wetenschapsdag Juni 2018

Methods III/IV - The questionnaire Example of case vignette (print screen) NHG Wetenschapsdag Juni 2018

Methods IV/IV- Statistics Proportion and 95% CI for categorized data Odd ratio’s (ORs) for GPs advising to stop statin treatment using mixed-effect logistic regression models accounting for clustering within GPs and country P-value <0.05 was considered statistically significant NHG Wetenschapsdag Juni 2018

Results I/IV Survey was send to 10,048 GPs across 30 countries Median response rate 35.5% (range 7.1-93.1) 2250 out of 2362 (95.3%) met the inclusion criteria Table 1. Baseline characteristics N (%) Female GP 1,211 (53.8) Practice location City Suburban Rural 1134 (50.4) 522 (23.7) 583 (25.9) Experience as GP < 5 years 5-20 years > 20 years 358 (15.9) 1024 (45.5) 865 (38.5) Self-estimated prevalence of > 80 years at own practice < 20% > 20% 1697 (75.4) 496 (22.0) Treatment is based on (inter-)national guidelines (Mainly) yes Neutral (Mainly) No 835 (42.9) 498 (25.6) 611 (31.4 JG: ik zou de getallen afronden naar hele getallen – dat lijkt me prachtig en meer dan genoeg NHG Wetenschapsdag Juni 2018

Results II/IV - results from the case vignettes Table 2. Percentages of general practitioners (GPs) advising to stop cholesterol treatment for the eight individual cases and the influence of a limited life expectancy Cases Case Characteristics Proportion of GPs stopping treatment Proportion of GPs stopping treatment when life expectancy is limited   Frailty CVD  Side effects % (95% CI) Overall  46.0 (44.9-47.1) 89.7 (88.7-90.7) Case 1 – 50.5 (48.1-52.8) 91.2 (89.8-92.5) Case 2 + 61.6 (59.4-63.9) 94.6 (93.5-95.6) Case 3 81.7 (79.8-83.4) 95.1 (94.0-96.1) Case 4 80.1 (78.2-82.0) 95.1 (94.8-96.7) Case 5 5.2 (4.2-6.3) 76.5 (74.5-78.5) Case 6 17.3 (15.6-19.1) 87.0 (85.4-88.6) Case 7 35.0 (32.8-37.3) 86.5 (84.8-88.0) Case 8 35.2 (33.0-37.5) 89.0 (87.4-90.4) 1 overall 46% of the cases were advised to stop statin treatment and almost 90% when life expectancy was less than 1 year 2.GPs were most divided on what to advise case nr 1 (a not frail patiënt without a history of CVD and no side effecrs); 50% of GPs advised to stop statin effects and about 50% did not advise to stop. When the same patiënt was said to have a short life expectancy aproximaley 91 % advised to stop. 3. Case 3 &4 describing frail cases on statin treatment for primary prevention, were most likely to be stopped. GPs were least likely to give a stop advise in case vignette 5, describing a non frail patiënt with CVD and without side effects, but when the same patiënt had a short life expectancy GPs were more likely to stop (76%) NHG Wetenschapsdag Juni 2018

Results III/IV- regression models Table 3. Association of patient characteristics and GPs’ treatment advice to stop statin treatment in oldest-old. Characteristic Univariate Multivariatea OR 95%CI ORadj Limited life expectancy 17.6 16.3 to 19.0 50.7 45.5-56.4 No cardiovascular disease 4.6 4.3 to 4.8 13.8 12.6-15.1 Frailty 2.1 2.0 to 2.2 4.1 3.8 -4.4 Side effects 1.3 1.2 to 1.4 1.6 1.5-1.7 Results from the mixed models All 4 characteristics were significatly associated with increased advice to stop statins Life expectancy and CVD had the highest odds for stopping. Frailty and side-effects were less important reasons to stop aAdjusted for GP characteristics (gender, experience, location, prevalence of oldest-old, guideline compliance) and patient characteristics (frailty, side effects, absence of cardiovascular disease and limited life expectancy < 1 year). NHG Wetenschapsdag Juni 2018

Results IV/IV- International treatment variation This map shows the treatment variation across the participating countries (27 European countries+ NZ, Israel and Brazil) It shows the % in which GPs decide to stop statin treatment in all 8 cases. The counrties in white were not participating in the study. In dark blue you see the countries with highest percentages to stop (e.g. Noway, germany, Denmark, Spain) In the lighter shades of blue you can see the countries in which GPs were less likely to advice to stop (such as the UK, Greece and Oekrain) NHG Wetenschapsdag Juni 2018

Conclusions Patient characteristics as frailty, side effects and limited life expectancy are reasons for GPs to advise stopping statin treatment in >80 year old patients. Statin treatment as secondary prevention is an important reason not to stop. Overall, and within all countries, short life expectancy was the strongest independent predictor of advice to stop statins. There is variation in treatment advice between GPs and across countries. NHG Wetenschapsdag Juni 2018

Clinical implications This study shows that there is considerable treatment variation between GP, especially in primary prevention. This study stresses the need for more research and clearer guidelines in this area. A better understanding of the risk-benefit profile of statins in older people is needed NHG Wetenschapsdag Juni 2018

Limit to the first 2 points for discussion NHG Wetenschapsdag Juni 2018

References 1Jansen et al. General practitioners Decision Making about Primary Prevention of Cardiovascular Disease in Older Adults: A Qualitative study. PloseOne, 2017. 12 (1): pe0170228 2 Fried et al. Frailty in older adults: evidence for a phenotype. J. Gerontol A Biol Sci Med Sci, 2001. 56(3):p M146-56 NHG Wetenschapsdag Juni 2018