No 51 - Statins - all you need to know
At the moment it feels like all I am doing is dishing out Statins to everyone. So, I thought I should read up on statins, their alternatives, their benefits and SE.
This is going to be short and succinct, whether you are a HCP or a patient, this may help you decide whether to take a statin or not.
To put my bias upfront, after reading around the subject, once I get into my 50s I will probably start taking a low dose statin - mostly because I’d like to live as long as possible and have the highest QOL (quality of life) that I can.
What is a statin?
statins = Hydroxymethyl glutaryl coenzyme A reductase (HMG-CoA) inhibitors
HMG-CoA is an enzyme in the liver
HMG-CoA, which is a rate limiting step in cholesterol synthesis
They are tablets that are prescribed to be taken daily, mostly before bed.
How do statins work?
The statin stops HMG-CoA producing cholesterol in the liver.
This can lower low density lipoprotein cholesterol (LDL-C) levels by 20-50%
And lower triglyceride levels 10-20%
It may also increase high density lipoprotein cholesterol (HDL-C) levels (5-10%)
By lowering the cholesterol in the blood, we think they reduce the amount of cholesterol that can go into plaques in arterial walls.
By preventing the arterial plaques getting any bigger, this can prevent them blocking the blood flow and therefore stop heart attacks, strokes and death.
What kind of statins are there?
Until recently, I hadn’t fully realised that there were different strengths of statins
6 = pitavastatin, atorvastatin, rosuvastatin, pravastatin, simvastatin and fluvastatin
Atorva can be taken any time of day, the weaker ones should be taken at night because that is when HMG-CoA is most active.
High = Atorva, Simva (high dose) and Rosuva
Med = low dose Atorva, Simva, Rosuva, and high dose Fluva
Low = Prava and Fluva
How effective are statins?
This is a more tricky question! The consensus is that on average statins prevent deaths, but it is more difficult to say if a statin will keep you, personally, alive longer.
Statins reduced all-cause mortality [odds ratio (OR) 0.86, 95% confidencre Interval (CI) 0.79-0.94] (In English, this means people died less often)
Statins reduced fatal and non-fatal cardiovascular events [relative risk (RR) 0.75 95% CI 0.67-0.80] (Heart attacks, MIs, sudden cardiac death, MACE)
Statins reduced the incidence of fatal and non-fatal stroke (RR 0.78, 95% CI 0.68-0.89)
An alternative way to look at the evidence of statins is that:
https://www.thennt.com/nnt/statins-persons-low-risk-cardi...
No statistically significant mortality benefit (People on average did not live any longer if they took a statin)
1 in 217 avoided a nonfatal heart attack (myocardial infarction)
1 in 313 avoided a nonfatal stroke
1 in 21 experienced pain from muscle damage
1 in 204 developed diabetes mellitus
How would statins best be used?
In an ideal healthcare system we would risk stratify all patients.
CAC score - Coronary Angiogram Calcium - is highly predictive of future MACE (heart attacks)
If the CAC score is low then the statin NNT to prevent one MACE = 87,
If the CAC score is high NNT = 18.
The NNT = the number needed to treat. This means that 18 people need to take a statin every day for about 5 years for 1 person to avoid a heart attack (which won’t necessarily kill them).
The reason all of the NNT quoted above are different is because they are from different studies, listed below.
What are the side effects of taking statins?
Must studies report no serious harm caused by statins.
10% of patients report muscle aches
0.1% might developed Rhabdomyalsis
Myopathy and rhabdomyolysis = estimated incidences of 5 cases per 100,000 person years and 1.6 cases per 100,000 person years, respectively. These conditions involve the muscle cells becoming damaged and releasing their contents into the blood. These conditions are very rare but this is why we recheck bloods before and after someone had started a statin.
1% of patients had deranged LFTs, but we don’t know if this actually causes any harm
Hyperglycaemia is noted to be relatively common and it is thought that this can increase the risk of developing type 2 diabetes
There have been yellow card warnings to the MHRA and FDA about an increase in cognitive decline and dementia after starting statins. It was thought that if cholesterol was lowered too much then this could affect brain cell function. However, recent studies have actually found that people on statins suffer from dementia less than those who did not take a statin.
In the BNF there is a long list of other multi-system non-specific side effects
How are statins monitored?
https://cks.nice.org.uk/topics/lipid-modification-cvd-pre...
Before starting you should check = LFT, HbA1c, TFT, Lipids, CK, U/E
At 3 months check = LFT, HbA1c
If muscle soreness = check CK
Annually = LFT, HbA1c, TFT, Lipids, CK, U/E - titrate up the dose if cholesterol is still high
What are the alternatives to statins?
The first option in preventative medicine is always - do nothing, or watch and wait. Some people don’t want an intervention or a risk score or a medication for life. If we don’t know that a medical intervention prolongs life, then this is sometimes the best approach.
Lifestyle and diet - it makes sense that if you change your diet then you should be able to reduce the amount of cholesterol and triglyceride fatty acids floating around in your blood. However, biology isn’t that simple and it is more difficul to achieve than most people imagine. This is especially true if you have genes that cause high cholesterol.
Ezetimibe is an alternative it statins are not tolerated
Ezetimibe = selective cholesterol absorption inhibitor
Ezetimibe reduces LDL-C modestly by about 18% but does not necessarily reduce the number of heart attacks or strokes or deaths.Fenofibrate = is a drug used to lower high TGs
They reduce LDL-C concentration by 18%–25%
They reduce TG by 40%–48%
They increase high-density lipoprotein cholesterol (HDL-C) by 35%–36%,A combination of low dose statin and Ezetimibe was found to lower cholesterol more than just a high dose statin. People reported fewer blood anormalities or side effects. However, the studies found that Ezetimibe and a statin or fenofibrate and a statin did not reduce deaths more than just a statin alone.
Useful Papers
Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, Ward K, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD004816. doi: 10.1002/14651858.CD004816.pub5. PMID: 23440795; PMCID: PMC6481400.
Ramkumar S, Raghunath A, Raghunath S. Statin Therapy: Review of Safety and Potential Side Effects. Acta Cardiol Sin. 2016 Nov;32(6):631-639. doi: 10.6515/acs20160611a. PMID: 27899849; PMCID: PMC5126440.
Zhang X, Wen J, Zhang Z. Statins use and risk of dementia: A dose-response meta analysis. Medicine (Baltimore). 2018 Jul;97(30):e11304. doi: 10.1097/MD.0000000000011304. PMID: 30045255; PMCID: PMC6078755.
Power MC, Weuve J, Sharrett AR, Blacker D, Gottesman RF. Statins, cognition, and dementia—systematic review and methodological commentary. Nat Rev Neurol. 2015 Apr;11(4):220-9. doi: 10.1038/nrneurol.2015.35. Epub 2015 Mar 24. PMID: 25799928; PMCID: PMC4458855.
Kemp EC, Ebner MK, Ramanan S, Godek TA, Pugh EA, Bartlett HH, McDonald JW, Mecca MC, van Dyck CH, Mecca AP; Alzheimer's Disease Neuroimaging Initiative. Statin Use and Risk of Cognitive Decline in the ADNI Cohort. Am J Geriatr Psychiatry. 2020 May;28(5):507-517. doi: 10.1016/j.jagp.2019.11.003. Epub 2019 Nov 11. PMID: 31806426; PMCID: PMC7170771.
Ah YM, Jeong M, Choi HD. Comparative safety and efficacy of low- or moderate-intensity statin plus ezetimibe combination therapy and high-intensity statin monotherapy: A meta-analysis of randomized controlled studies. PLoS One. 2022 Mar 4;17(3):e0264437. doi: 10.1371/journal.pone.0264437. PMID: 35245303; PMCID: PMC8896700.
Zhan S, Tang M, Liu F, Xia P, Shu M, Wu X. Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events. Cochrane Database Syst Rev. 2018 Nov 19;11(11):CD012502. doi: 10.1002/14651858.CD012502.pub2. PMID: 30480766; PMCID: PMC6516816.
Oikawa S, Yamashita S, Nakaya N, Sasaki J, Kono S; Effect of Fenofibrate and Ezetimibe Combination Treatment on Lipid (EFECTL) Study Investigators. Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study. J Atheroscler Thromb. 2017 Jan 1;24(1):77-94. doi: 10.5551/jat.35626. Epub 2016 Jul 8. PMID: 27397061; PMCID: PMC5225135.
Heller DJ, Coxson PG, Penko J, Pletcher MJ, Goldman L, Odden MC, Kazi DS, Bibbins-Domingo K. Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary Prevention of Coronary Heart Disease and Stroke. Circulation. 2017 Sep 19;136(12):1087-1098. doi: 10.1161/CIRCULATIONAHA.117.027067. Epub 2017 Jul 7. PMID: 28687710; PMCID: PMC5605438.
Mortensen MB, Nordestgaard BG. Statin Use in Primary Prevention of Atherosclerotic Cardiovascular Disease According to 5 Major Guidelines for Sensitivity, Specificity, and Number Needed to Treat. JAMA Cardiol. 2019;4(11):1131–1138. doi:10.1001/jamacardio.2019.3665
Mortensen MB, Falk E, Li D, Nasir K, Blaha MJ, Sandfort V, Rodriguez CJ, Ouyang P, Budoff M. Statin Trials, Cardiovascular Events, and Coronary Artery Calcification: Implications for a Trial-Based Approach to Statin Therapy in MESA. JACC Cardiovasc Imaging. 2018 Feb;11(2 Pt 1):221-230. doi: 10.1016/j.jcmg.2017.01.029. Epub 2017 Jul 25. PMID: 28624395; PMCID: PMC5723240.