Journal Article

The effect of adherence to statin therapy on cardiovascular mortality: quantification of unmeasured bias using falsification end-points

Bijlsma, Maarten J., Vansteelandt, Stijn, Janssen, Fanny, Hak, Eelko

2016

Overview

Background To determine the clinical effectiveness of statins on cardiovascular mortality in practice, observational studies are needed. Control for confounding is essential in any observational study. Falsification end-points may be useful to determine if bias is present after adjustment has taken place. Methods We followed starters on statin therapy in the Netherlands aged 46 to 100 years over the period 1996 to 2012, from initiation of statin therapy until cardiovascular mortality or censoring. Within this group ( n  = 49,688, up to 16 years of follow-up), we estimated the effect of adherence to statin therapy (0 = completely non-adherent, 1 = fully adherent) on ischemic heart diseases and cerebrovascular disease (ICD10-codes I20-I25 and I60-I69) as well as respiratory and endocrine disease mortality (ICD10-codes J00-J99 and E00-E90) as falsification end points, controlling for demographic factors, socio-economic factors, birth cohort, adherence to other cardiovascular medications, and diabetes using time-varying Cox regression models. Results Falsification end-points indicated that a simpler model was less biased than a model with more controls. Adherence to statins appeared to be protective against cardiovascular mortality (HR: 0.70, 95 % CI 0.61 to 0.81). Conclusions Falsification end-points helped detect overadjustment bias or bias due to competing risks, and thereby proved to be a useful technique in such a complex setting.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Aged / Aged, 80 and over / Bias / Biostatistics / Biostatistics and methods / Cardiovascular / Cardiovascular diseases / Cardiovascular Diseases - drug therapy / Cardiovascular Diseases - mortality / Cerebrovascular diseases / Codes / Coronary artery disease / Demographics / Demography / Diabetes mellitus / Disease control / Drug stores / Economic factors / Endocrine disorders / Environmental Health / Epidemiology / Estimates / Evaluation / Falsification end-points / Female / Follow-Up Studies / Forecasts and trends / Health care / Heart diseases / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use / Ischemia / Male / Medication Adherence - statistics & numerical data / Medicine / Medicine & Public Health / Middle Aged / Mortality / Neighborhoods / Netherlands - epidemiology / Observational studies / Overadjustment / Patient compliance / Patients / Pharmacy / Prognosis / Proportional Hazards Models / Public Health / Regression analysis / Regression models / Research Article / Risk / Social factors / Socioeconomics / Starters / Statin therapy / Statins / Studies / Therapy / Vaccine / Variables / Vascular diseases