Summary
Background
The effect of statins on the prevention of cardiovascular events is well-established. However, a recent controversy in France questioned the value of statins, especially in primary prevention.
Aims
To evaluate the impact of this controversy on patient adherence to statin therapy and its potential clinical impact.
Methods
All patients on statins were recruited consecutively from consultations over a period of 1 month (from March 2013) by five physicians in three centres. Patient demographics and co-morbidities were collected and adherence to statin therapy was evaluated with a questionnaire. We estimated the number of deaths and major cardiovascular events that could be induced per year.
Results
A total of 142 patients were included: 37 in primary prevention (mean age, 68.0 ± 13.1 years; 41% women); 105 in secondary prevention (mean age, 67.6 ± 12.1 years; 20% women). In primary prevention, 24.3% of patients intended to stop statins versus 8.6% in secondary prevention ( P < 0.001). In France, if the percentages of medication discontinuations following the controversy were actually similar to those we found in our survey, 4992 major cardiovascular events, including 1159 deaths, would be induced in 1 year.
Conclusion
Recent controversy over statins could induce a large proportion of patients to stop their medication and generate a large number of major cardiovascular events.
Résumé
Contexte
Les bénéfices des statines sur la prévention des événements cardiovasculaires sont aujourd’hui bien démontrés. Récemment, en France, une polémique a remis en cause l’intérêt des statines, notamment en prévention primaire.
Objectif
Évaluer l’impact de cette polémique sur l’observance des patients vis-à-vis des statines.
Méthodes
Tous les patients sous statines ont été recrutés consécutivement en consultations pendant une période de 1 mois (en mars 2013) par 5 cardiologues au sein de 3 centres. Les caractéristiques démographiques, les comorbidités ont été collectées et l’adhérence aux statines évaluée par un questionnaire. Nous avons estimé le nombre de décès et d’événements cardiovasculaires majeurs que cette polémique pourrait engendrer à partir des données actuelles.
Résultats
Cent-quarante patients ont été inclus: 37 en prévention primaire (âge moyen, 68,0 ± 13,1 ; 41 % femme); 105 en prévention secondaire (âge moyen, 67,6 ± 12,1 ; 20 % femme). En prévention primaire, 24,3 % des patients interrogés ont déclaré avoir l’intention d’arrêter les statines contre 8,6 % prévention secondaire ( p < 0,001). En France, cette polémique pourrait engendrer 4992 événements cardiovasculaires majeurs dont 1159 décès par an si les patients arrêtent réellement leur statine.
Conclusion
La polémique récente sur les statines pourrait entraîner l’arrêt de ces traitements chez de nombreux patients et ainsi provoquer la survenue de nombreux d’évènements cardiovasculaires majeurs.
Introduction
Randomized controlled clinical trials and meta-analyses have shown statins to be beneficial in decreasing morbid and mortal cardiovascular events in apparently healthy individuals and in those with clinically evident cardiovascular disease . However, a recent controversy in France questioned the value of statins, especially in primary prevention, in which the cost-effectiveness of treatment is more complex to assess . Therefore, we aimed to evaluate the impact of this controversy on patient adherence to statin therapy and its potential clinical impact.
Methods
Patient population
All patients on statins were recruited consecutively from outpatient consultations over a period of 1 month (from March 2013) by five physicians (L.S., L.P., D.B., N.D. and E.P.) in three centres (including two university hospitals and one private centre).
Patients were included regardless of the type of cardiovascular event prevention (primary or secondary).
Data collection
Data were recorded on dedicated questionnaires at each centre by the consulting physicians and entered into a common database. The following data were prospectively collected and electronically stored for each patient: demographic characteristics (age, sex and body mass index [BMI]), cardiovascular risk factors (arterial hypertension, diabetes, current smoking, hyperlipidaemia) and medical cardiovascular history (presence of prior acute myocardial infarction [MI], prior percutaneous coronary intervention [PCI], prior coronary artery bypass graft [CABG], peripheral artery disease, chronic kidney disease). Chronic kidney disease was defined as creatinine clearance < 30 mL/minute or creatinine < 15 mg/L.
Regarding adherence to statin therapy, for each patient we collected the indication for statin treatment (primary or secondary prevention) and the type, dose, duration and potential side-effects of the statin used.
During the consultation, the physician initially did not allude to the statin controversy, in order to assess whether the patient mentioned it spontaneously; if they did not, the physician asked the patient at the end of the consultation whether they had heard of the controversy. In all cases, patients were asked whether they intended to stop their statin treatment as a consequence of the controversy.
One-year potential clinical impact
For this study, we made the conservative assumption that patients stopping statins would have a 1 mmol/L increase in low-density lipoprotein (LDL) (the average effect of the lowest dose of any statin available is about a 1.5 mmol/L reduction in LDL) . Using the Cholesterol Treatment Trialists’ collaboration meta-analysis and data from the National Health Insurance System on statin consumption according to the presence of cardiovascular history , we evaluated the potential clinical impact of this controversy in terms of cardiovascular events (including death, non-fatal MI or stroke) and cardiovascular death.
In primary prevention, the National Health Insurance System estimated that 8.7% people used statins in France (i.e. 5046 million). Results of the meta-analysis showed a reduction of 1.44 cardiovascular events per 100 person-years on statins (risk reduction, 25% per mmol) and 0.53 cardiovascular deaths per 100 person-years (risk reduction, 15%).
In secondary prevention, the National Health Insurance System estimated that 70.7% people used statins in France (i.e. 1218 million). Results of the meta-analysis showed a reduction of 3.27 cardiovascular events per 100 person-years on statins (risk reduction, 21% per mmol) and 1.76 cardiovascular deaths per 100 person-years (risk reduction, 12%).
Statistical analysis
Statistical analyses were performed using Stata software (version 12; StataCorp LP, College Station, TX, USA) or SPSS software (version 20.0; IBM, Armonk, NY, USA). For quantitative variables, means, standard deviations and minimum and maximum values were calculated. In addition, medians with interquartile ranges were calculated for some variables. Discrete variables are presented as percentages. Comparisons were made using the chi-square test or Fisher’s exact test for discrete variables and using unpaired t -tests, the Wilcoxon signed-rank test or one-way analyses of variance for continuous variables. Odds and hazard ratios are given with their 95% confidence intervals. For all analyses, a P value < 0.05 was considered significant.
Results
Over a 1 month period, a total of 142 patients were included in this study.
Baseline characteristics
Baseline clinical characteristics of patients on statins according to the type of prevention are summarized in Table 1 . Most patients were followed for secondary prevention (74%). The mean age was similar in both groups. The proportion of women was higher in primary prevention. In addition, the proportions of diabetes, current smoking, hyperlipidaemia, obesity (BMI > 30 kg/m 2 ) and chronic renal insufficiency were similar in both groups; however, more patients on statins for primary prevention had hypertension.
| Primary prevention | Secondary prevention | P | |
|---|---|---|---|
| ( n = 37) | ( n = 105) | ||
| Age (years) | 68.0 ± 13.1 | 67.6 ± 12.1 | 0.86 |
| Women | 15 (41) | 21 (20) | 0.01 |
| BMI (kg/m 2 ) | 25.8 ± 4.2 | 26.5 ± 6.8 | 0.58 |
| Hypertension | 31 (84) | 60 (66) | 0.04 |
| Diabetes mellitus | 8 (22) | 33 (31) | 0.26 |
| Current smoking | 2 (5) | 16 (15) | 0.12 |
| Hyperlipidaemia | 30 (81) | 75 (74) | 0.36 |
| Previous MI | 0 (0) | 66 (63) | < 0.001 |
| Previous PCI | 0 (0) | 69 (66) | < 0.001 |
| Previous CABG | 0 (0) | 20 (19) | 0.004 |
| Peripheral artery disease | 0 (0) | 10 (10) | 0.05 |
| Chronic renal insufficiency | 9 (24) | 18 (17) | 0.34 |
Participating centres
Patients were enrolled by five physicians (cardiologists) in three hospitals: two university hospitals (the Necker Hospital and the Georges-Pompidou European Hospital, in Paris) and one private centre (in Issy-les-Moulineaux). No significant difference was observed according to centre.
Impact of statin controversy
Overall, 23% of patients spontaneously talked of the controversy over statins during the consultation and 68% were aware of it. No difference was observed in terms of the type of prevention (27% vs 22%, P = 0.53 and 62% vs 70%, P = 0.75, respectively). In primary prevention, 19% of patients had doubts about the benefits of treatment versus 10% in secondary prevention ( P = 0.13). Sixty-five percent of patients agreed to take generic drugs and 53% reported reading patient information leaflets for their medications (no difference in terms of the type of prevention).
All patients had statins for primary or secondary prevention ( Table 2 ). Rosuvastatin and atorvastatin were the most commonly used statins, whatever the type of prevention. Ezetimibe was used in 5% for primary prevention and in 9% for secondary prevention. Adverse events (muscular weakness, stiffness or pain) were reported in 27% in primary prevention and in 21% in secondary prevention. The median LDL cholesterol concentration was 108 mg/L (interquartile range, 95–137) in primary prevention and 82 mg/L (interquartile range, 64–101) in secondary prevention.
