Statin Use Clinically, statins are prescribed to people who fail to have meaningful reduction of lipid panel values after attempting the following interventions: – Lifestyle Modification – Healthier Diet – Increased Physical Exercise How many people succeed with these interventions? Who benefits from statins?
Lipid-lowering guidelines EBM? 2001, Americans on statins ↑ from 13M to 36M based on NCEP ATP III guidelines – Most of these people in “moderate” risk group No clinical evidence of occlusive disease ? What percentage of people on statins are in: – High risk group: – Moderate risk group: – Low risk group:
Statin Usefulness Primary prevention? – Elevated lipids w/o history of heart disease
Why statins fail in primary prevention Current guidelines are based on the assumption that cardiovascular risk is a continuum ASSUMES that evidence of beneﬁt in people with occlusive vascular disease (secondary prevention) can be extrapolated to primary prevention populations This assumption, plus the assumption that cardiovascular risk can be accurately predicted, leads to the recommendation that a substantial proportion of the healthy population should be placed on statin therapy
Statin Usefulness Secondary prevention? – Decreasing mortality in people with pre-existing CVD
Statin Usefulness Secondary prevention? – Decreasing mortality in people with pre-existing CVD BULLSHIT
What you see as a practicing physician ACP Internist Newsletter, 03/03/2014
Statin challenges may allow some with myalgia to continue their regimen
November 2013 Pooled Cohort Eq. Predicts 10-year Risk
2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol
High-intensity therapy for ♂ and ♀ < 75 with clinical ASCVD LDL-c > 190 mg/dL or TG > 500 mg/dL evaluate for secondary causes of hyperlipidemia Moderate-intensity therapy for 40-75 yo IDDM LDL-c 70-189mg/dL, w/o clinical ASCVD OR DM should be treated w/ moderate-to-high- intensity therapy
Lower cholesterol as much as possible? Recently, Getz et al calculated that in Norway, one of the healthiest nations in the world, about 85% of men and more than 20% of the women over age 40 would be classified as high risk using the new criterion. If followed, the new recommendations might therefore put most of the Western world’s adult population on statin therapy.
Are high statin doses safe? In the Treating to New Targets (TNT) trial, the only study comparing a low and high dose of the same statin, not even 80 mg atorvastatin was able to lower mean low density lipoprotein cholesterol below 1.81 mmol/l. Clinical experience has taught us that a dose increase of that size of any drug will inevitably increase both the number and the seriousness of side effects. This apparently did not concern the authors, who concluded, “Intensive lipid lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD [coronary heart disease] provides significant clinical benefit.”
Are high statin doses safe? In the Incremental Decrease in End points through Aggressive Lipid lowering (IDEAL) trial, which compared usual dose simvastatin with 80 mg atorvastatin, no significant difference was seen on the major end points. 90% of participants in both groups had side effects, and in almost half of them they were recorded as serious. The authors of the IDEAL trial did not comment on this except that, “there was no difference between the groups in the frequency of adverse events that were rated as serious”; neither did they inform readers about the nature of these events.
Adverse effects of statins Heart failure: – Inhibit the synthesis of hydroxymethylglutaryl coenzyme A reductase, an enzyme involved in synthesis of the precursor of cholesterol and other important molecules such as coenzyme Q10, vital for mitochondrial energy production. – Thus statins lowerplasma Q10 concentrations and worsen cardiac function in patients with heart failure, and oral coenzyme Q10 can improve or prevent this serious complication. – Heart failure has not been reported with statins, possibly because it has been seen to be the result of the primary disease rather than an adverse effect but also because patients with imminent or manifest congestive failure are routinely excluded from statin trials.
Adverse effects of statins Myalgia and rhabdomyolysis: – Claimed to occur in less than 1% of patients taking statins – 22 professional athletes with familial hypercholesterolaemia who were treatedwith various statins, sixteen discontinued the treatment because of muscle side effects 4.2 cases of rhabdomyolysis per 100 000 patient years after atorvastatin treatment – Relative risk increase of 100% in untreated
Adverse effects of statins Mental and neurological symptoms: – Cholesterol is required for your brain to work – Severe irritability, aggressive behaviour, suicidal impulses, cognitive impairment, memory loss, global amnesia, polyneuropathy, and erectile dysfunction. – In many cases the symptoms were reversible and re-occurred after re-challenge.
Adverse effects of statins Cancer: – Problem with followup Significant increase in breast cancer was seen in the cholesterol and recurrent events trial (CARE), with most cases being recurrences. – Since then patients with a history of cancer have been excluded from statin trials To my knowledge, no trial has analyzed cancer incidence separately for smokers and nonsmokers. In the trial of pravastatin in elderly individuals at risk of vascular disease (PROSPER), the only statin trial exclusively in elderly people, the significant increase in cancer mortality neutralized the benefit from fewer cardiovascular deaths. – Finding dismissed by referring to a meta-analysis of all statin trials that failed to find an association with cancer, but the authors ignored mentioning that the mean age of participants in these trials was about 25 years lower than in PROSPER.
Simvastatin impairs exercise training adaptations J Am Coll Cardiol. 2013 Aug 20;62(8):709- 14. doi: 10.1016/j.jacc.2013.02.074. Epub 2013 Apr 10 37 participants (exercise plus statins: n = 18; exercise only: n = 19) completed the study. Cardiorespiratory fitness increased by 10% (p < 0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (p < 0.005). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise-only group (p < 0.05), but decreased by 4.5% in the simvastatin-plus-exercise group (p < 0.05) Simvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients at risk of the metabolic syndrome.