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LDL Cholesterol Particle Size and Number What Gives ?

Posted on February 27, 2018

LDL Particle Size and Particle Number, What Gives?

Ron is a 72 year old retired engineer, and has a total cholesterol of 174 which hasn’t changed over the seven years we have been following him. This is quite low. Yet, Ron is concerned because his LDL particle number and LDL particle size are “outside of the lab range”.  He is very worried about this and is concerned about his risk for future heart attack.  I explained to Ron the lab range doesn’t apply to him.  Ron’s Calcium Score is low, and his total cholesterol is 174, and he does not have metabolic syndrome or diabetes, so he doesn’t need to worry about the LDL particle size or particle number.

What does the mainstream cardiology say about the value of LDL particle size and number?

The Quebec Study – Small Dense LDL Associated with Increased Mortality from Coronary Artery Disease

You might say “wait just a minute here”, the Quebec study followed 2072 males over 13 years and found that small dense LDL was associated with increased mortality from cardiovascular disease above chart).(6)  The above chart is very convincing, and the three lines for small dense LDL are nicely separated. (6) However, as pretty as the above chart looks, Correlation is not necessarily causation.  If increased small dense LDL particle number causes coronary artery disease, then an intervention that reduces small dense LDL particles should be preventive.  However we know that it is not. Above image courtesy of Medscape.

Houston, We Have a Problem,  New Drug Reduces Small LDL,

However, No Benefit in Preventing Heart Disease

Treatment with the new cholesterol lowering drug, Evacetrapib, resulted in significant decreases in “total LDL particle number (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations”.(5) Yet, according to Dr Lincoff in NEJM 2017,

“treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease.”(4)

As a matter of fact, Eli Lilly abandoned drug development after this failed study.(4)  So we see that reducing total LDL particle number, or increasing LDL particle size had no benefit for preventing death from heart disease.  The benefit was same as a placebo.

Dr Allaire  agrees that LDL particle size is not very useful.  Dr Allaire writes in 2017 Current Opinion in Lipidology:(1)

“LDL particle size….has not been independently associated with CVD risk after adjustment for other risk factors such as LDL cholesterol, triglycerides, and HDL-C and that routine use of information pertaining to particle size to determine and manage patients’ risk is not yet justified.”(1)

In other words, according to Dr Allaire,  the LDL particle size is not a good predictor of cardiovascular risk.(1)

Predicting Risk: LDL Subfraction Vs. Calcium Score

The next question you might ask: “If LDL cholesterol is not helpful, then what other test is useful for predicting risk of cardiovascular disease?” 

The answer is the Calcium Score which is an inexpensive test which uses a CAT scan to measure the amount of calcium in the coronary arteries.  Studies show that the higher the number the greater the risk, the lower the number the smaller the risk.  None of the cholesterol subfractions can provide this type of information, and in my opinion should be relegated to the medial museum, as a relic from the past.

Conclusion: When it comes down to a contest between LDL Cholesterol Subfractions and Calcium Score, there is no contest.  The Calcium Score wins every time.

Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie Florida 33314
954 792-4663

Articles with Related Interest

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Statin Denialism Internet cult

Links and References

Header Image LDL particle courtesy of Drs Wolfson

1) Curr Opin Lipidol. 2017 Jun;28(3):261-266. LDL particle number and size and cardiovascular risk: anything new under the sun? Allaire J1, Vors C, Couture P, Lamarche B.

LDL particle size, on the other hand, has not been independently associated with CVD risk after adjustment for other risk factors such as LDL cholesterol, triglycerides, and HDL-C and that routine use of information pertaining to particle size to determine and manage patients’ risk is not yet justified.

We provide here an up-to-date perspective on the potential use of LDL particle number and size as complementary risk factors to predict and manage cardiovascular disease (CVD) risk in the clinical realm.
RECENT FINDINGS:  Studies show that a significant proportion of the population has discordant LDL particle number and cholesterol indices [non-HDL cholesterol (HDL-C)]. Data also show that risk prediction may be improved when using information on LDL particle number in patients with discordant particle number and cholesterol data. Yet, most of the current CVD guidelines conclude that LDL particle number is not superior to cholesterol indices, including non-HDL-C concentrations, in predicting CVD risk. LDL particle size, on the other hand, has not been independently associated with CVD risk after adjustment for other risk factors such as LDL cholesterol, triglycerides, and HDL-C and that routine use of information pertaining to particle size to determine and manage patients’ risk is not yet justified.
SUMMARY:  Additional studies are required to settle the debate on which of cholesterol indices and LDL particle number is the best predictor of CVD risk, and if such measures should be integrated in clinical practice.

Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes

2) Clin Chem. 2017 Apr;63(4):870-879. doi: 10.1373/clinchem.2016.264515. Epub 2017 Feb 7.  Discordance between Circulating Atherogenic Cholesterol Mass and Lipoprotein Particle Concentration in Relation to Future Coronary Events in Women.
Lawler PR1,2,3,4, Akinkuolie AO1,3, Ridker PM2,3, Sniderman AD5, Buring JE3,4, Glynn RJ3,4, Chasman DI3, Mora S6,2,3.
It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant.
METHODS:Among 27533 initially healthy women in the Women’s Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models.
RESULTS:Although all 3 biomarkers were correlated (r ≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both P < 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to nonHDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical risk factors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk.
CONCLUSIONS:Discordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement of lipoprotein particle concentration might better inform CHD risk assessment.

3)   Curr Opin Endocrinol Diabetes Obes. 2018 Jan 10. Discordance between lipoprotein particle number and cholesterol content: an update.
Cantey EP1, Wilkins JT2.
The cholesterol content within atherogenic apolipoprotein-B (apoB) containing lipid particles is the center of consensus guidelines and clinicians’ focus whenever evaluating a patient’s risk for atherosclerotic cardiovascular disease. The pathobiology of atherosclerosis requires the retention of lipoprotein particles within the vascular intima over time followed by maladaptive inflammation resulting in plaque formation and rupture in some. The cholesterol content is widely variable within each particle creating either cholesterol-deplete or cholesterol-enriched particles. This variance in particle cholesterol content varies within and between individuals. Discordance analysis exploits this difference in cholesterol content of particles to demonstrate the differential significance of LDL-cholesterol (LDL-C) and non-HDL-C from measures of lipoprotein particle number in terms of assessing atherosclerotic cardiovascular disease risks.
RECENT FINDINGS:Three studies have added to the growing body of literature of discordance analysis. Despite wide variability of discordance cutoffs, baseline risk of atherosclerotic disease, and populations sampled, the conclusion remains the same: risk of atherosclerotic disease follows apoB lipid particle concentration rather than cholesterol content of lipid particles.
SUMMARY:In addition to traditional lipid fractions, assessments of atherogenic particle number should be strongly considered whenever assessing CVD risk in nontreated and treated individuals. There is a need for clinical trials that focus not only on the reduction in LDL-C but apoB, as well.

4)  Lincoff, A. Michael, et al. “Evacetrapib and cardiovascular outcomes in high-risk vascular disease.” New England Journal of Medicine 376.20 (2017): 1933-1942.

Although treatment with evacetrapib has resulted in reductions of 60 to 70% in the levels of small dense LDL particles,29 effects on the total number of LDL particles and on apolipoprotein B levels (reductions of 22% and 20%, respectively) are considerably less pronounced.

CONCLUSIONS:Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease.

5)  Nicholls SJ, Ruotolo G, Brewer HB, et al. Evacetrapib alone or in combination with statins lowers lipoprotein(a) and total and small LDL particle concentrations in mildly hypercholesterolemic patients. J Clin Lipidol 2016;10:519-527.e4

Potent CETP inhibitors reduce plasma concentrations of atherogenic lipoprotein biomarkers of cardiovascular risk.
OBJECTIVES:To evaluate the effects of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, as monotherapy or with statins, on atherogenic apolipoprotein B (apoB)-containing lipoproteins in mildly hypercholesterolemic patients.
METHODS:VLDL and LDL particle concentrations and sizes (using nuclear magnetic resonance spectroscopy) and lipoprotein(a) concentration (using nephelometry) were measured at baseline and week 12 in a placebo-controlled trial of 393 patients treated with evacetrapib as monotherapy (30 mg/d, 100 mg/d, or 500 mg/d) or in combination with statins (100 mg plus simvastatin 40 mg/d, atorvastatin 20 mg/d, or rosuvastatin 10 mg/d; Clinicaltrials.gov Identifier: NCT01105975).
RESULTS:Evacetrapib monotherapy resulted in significant placebo-adjusted dose-dependent decreases from baseline in Lp(a) (up to -40% with evacetrapib 500 mg), total LDL particle (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations. Compared to statin alone, coadministration of evacetrapib and statins also resulted in significant reduction from baseline in Lp(a) (-31%), LDL-P (-22%), and sLDL (-60%) concentrations. The percentage of patients with concentrations above optimal concentrations for LDL-P (>1000 nmol/L) and sLDL (>600 nmol/L) decreased from 88% and 55% at baseline, respectively, to 20% and 12% at week 12, for patients treated with evacetrapib plus statins. Evacetrapib, alone or with statins, significantly increased LDL-P size.

CONCLUSIONS:Evacetrapib, as monotherapy or with statins, significantly reduces the concentrations of atherogenic apoB-containing lipoproteins, including Lp(a), LDL-P, and sLDL.

6) St-Pierre, Annie C., et al. “Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study.” Arteriosclerosis, thrombosis, and vascular biology 25.3 (2005): 553-559.Low density lipoprotein Risk of ischemic heart disease Quebec St Pierre Annie Arterio thrombo vasc bio 2005

The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Quebec Cardiovascular Study.
METHODS AND RESULTS:Cholesterol levels in the large and small LDL subfractions (termed LDL-C> or =260A and LDL-C<255a 13="" 2072="" 262="" a="" all="" and="" angina="" at="" baseline="" cardiovascular="" cohort="" coronary="" death="" during="" electrophoresis="" estimated="" events="" examination="" first="" followed-up="" for="" free="" from="" gel="" gradient="" ihd="" in="" infarction="" men="" myocardial="" nbsp="" nonfatal="" of="" pectoris="" period="" plasma="" polyacrylamide="" population-based="" quebec="" recorded.="" respectively="" strong="" study.="" style="border: 0px; font-family: inherit; font-style: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;" the="" unstable="" were="" which="" whole="" years="">Our study confirmed the strong and independent association between LDL-C<255a a="" and="" as="" dense="" ihd="" in="" ldl="" levels="" men="" of="" phenotype="" proxy="" risk="" small="" strong="" the="">, particularly over the first 7 years of follow-up. However, elevated LDL-C> or =260A levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76; P=0.07).

CONCLUSIONS:These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.

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Read the complete article here.

Why I won’t take statins for my high cholesterol - Julianne

Why I won’t take statins for my high cholesterol

In Summary, for those who took the statin for 5 years (with known heart disease):

Benefits in NNT

• 1 in 83 were helped (life saved)
• 1 in 39 were helped (preventing non-fatal heart attack)
• 1 in 125 were helped (preventing stroke)

Harms in NNH

• 1 in 100 were harmed (develop diabetes*)
• 1 in 10 were harmed (muscle damage)

If you have had a heart attack and change your diet to a Mediterranean diet – you will get far more benefit than Statin drugs:

In Summary, for those who adhered to the Mediterranean diet:

Benefits in NNT

• 1 in 18 were helped (preventing repeat heart attack)
• 1 in 30 were helped (preventing death)
• 1 in 30 were helped (preventing cancer)

Harms in NNH

• None were harmed

 

 

And if you want to prevent heart disease the Mediterranean diet is also far more effective than statin drugs:

 

In Summary, for those who ate the Mediterranean diet:

Benefits in NNT

• 1 in 61 were helped (avoiding a stroke, heart attack, or death)

Harms in NNH

• None were harmed (diet effects)

Read the full article here.

Statins in the Drinking Water? - Packer

Statins in the Drinking Water?

by Milton Packer, MedPage Today

"Universal treatment for people at minimal risk means that a physician would need to treat more than 100 patients for 10 years to obtain an extra year of good health in one person. This marginal improvement does not meet most current standards for cost-effectiveness. The benefit is so small that it disappears if quality of life were even slightly diminished by the need to remember to take the drug daily."

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"Treating every middle-aged person with a statin is the polar opposite of precision medicine.

Confused? You should not be. It is medicine that has gone insane."

Read the complete article here.

The High-Cholesterol Paradox - Wainwright

The High-Cholesterol Paradox

"Being told you have ‘high cholesterol’ is commonly taken as a sign of an unhealthy destiny. Research suggests that for many elderly people the news that they have ‘high cholesterol’ is more often associated with good health and longevity . For over 50 years this has been a paradox, the ‘High-Cholesterol Paradox’. What is really going on? "

Our review found that cholesterol lowering therapies were implicated in:

• Damage to muscles (including the heart) and exercise intolerance
• Increased risk of Dementias (Impaired Synaptogenesis and Neurotransmission)
• Failure of Myelin Maintenance (Multiple Sclerosis Risks)
• Neuro-muscular problems, aches and pains (Amyotrophic Lateral Sclerosis)
• Diabetes (Insulin release inhibited)
• Poor Maintenance of Bones and Joints
• Suppression of protective skin secretions (Apo-B) and increased MRSA infection

We have found compelling evidence that cholesterol-sulphate is vital to good vascular health so the question is..... Why would anyone want to lower cholesterol? What is needed is a lowering of damage to lipids - caused by sugar.


Read the complete article here.

The Elderly on Primary-Prevention Statins: No Survival Gains in ALLHAT - Medscape

The Elderly on Primary-Prevention Statins: No Survival Gains in ALLHAT

CHICAGO, IL — Statins for primary prevention do not lower the risk of death, whether cardiovascular or from any cause, when given to people aged 65 years or older with CV risk factors, suggests a secondary analysis of a major trial that caused a stir 15 years ago^[1].
The ALLHAT-LLT trial had randomized >10,000 people aged >55 with dyslipidemia and hypertension but no clinical heart disease to receive open-label pravastatin 40 mg/day or usual care. In its 2002 publication^[2], the trial famously saw no significant mortality reduction for the statin after 6 years, nor an improvement in fatal or nonfatal coronary heart disease events.

The results were similar in the new post hoc analysis of the trial focusing on the 2867 participants aged 65 years and older, as a whole and by the two age groups 65 to 74 years and >75 years, according to a report published May 22, 2017 in JAMA Internal Medicine with lead author Dr Benjamin H Han (New York University Langone School of Medicine, NY).
Although no significant outcomes differences were seen between the two randomized groups in any of the age categories, there was a trend (P=0.07) for increased all-cause mortality on the statin in the oldest age group.

As Han pointed out for heartwire from Medscape, the overall trial had well-recognized limitations. For example, the statin was given on an open-label basis. Also, it has been long noted that the ALLHAT-LLT usual-care group could receive statins at the physicians' discretion, which could potentially blur any differences in treatment outcomes.

Calls for Caution

"I would be very cautious in drawing any real conclusions from this study, as the study was not specifically designed to study statins in older adults, so all of the analyses are underpowered. None of their major conclusions were statistically significant," according to Dr Ann Marie Navar (Duke Clinical Research Institute, Durham, NC), who isn't connected with the ALLHAT-LLT report.
"Most statin trials have shown no difference in mortality, but [they showed] that statins do reduce the risk of coronary heart disease, a trend also seen in this secondary analysis," Navar told heartwire by email.

"The trend toward increasing mortality is certainly provocative but really needs to be explored in a trial specifically designed to test this issue."
The post hoc analysis included 1467 participants who had been randomized to pravastatin; their mean age was 71.3, and 48% were women. Their mean LDL-C level was 147.7 mg/dL at baseline and 109.1 mg/dL after 6 years.
The 1400 participants in the usual-care group had a mean age of 71.2 years, and 51% were female. Their mean LDL-C level was 147.6 mg/dL at baseline and 128.8 mg/dL after 6 years.
For all patients over the age of 65 who took pravastatin, the hazard ratio for all-cause mortality was 1.18 (95% CI 0.97–1.42, P=0.09) compared with the usual-care group. It was 1.08 (95% CI 0.85–1.37, P=0.55) for the 65–74 group and 1.34 (95% CI 0.98-1.84 P=0.07) for those aged 75 and older. Nor were there significant HRs for the secondary CHD end points.

In multivariate analysis, the corresponding HRs were 1.15 (95% CI 0.94–1.39) for 65 and older, 1.05 (95% CI 0.82–1.33) for those 65 to 74, and 1.36 (95% CI, 0.98-1.89) for 75 and older. The prospectively defined covariates included age, sex, race/ethnicity, primary-prevention aspirin use, smoking history, type 2 diabetes, body mass index, and systolic and diastolic blood pressures.

The Issues
"We are seeing a lot more older adults being put on statins for primary prevention, but the problem is, the evidence for doing so is limited," Han said.

"As geriatricians, we emphasize that treatment recommendations really need to be individualized with patients and need to also take into account not just what their cardiovascular risk is, but what their life expectancy is, what other competing risks they may have, and what their functional status and everyday activities are," Han observed.

Moreover, "for older adults, taking another medicine every day for the rest of your life isn't a small thing, especially if you have other chronic conditions, and right now we don't have any evidence that there's any benefit to doing so if you do not have any history of cardiovascular disease."

An editor's note accompanying the ALLHAT-LLC report points out the potential risks of extending statins to groups that may be unlikely to benefit clinically^[3]. For example, statin therapy may be associated with myopathy, myalgias, muscle weakness, and arthropathies, notes Dr Gregory Curfman (Harvard Medical School, Boston, MA).

"These disorders may be particularly problematic in older people and may contribute to physical deconditioning and frailty. Statins have also been associated with cognitive dysfunction, which may further contribute to reduced functional status, risk of falls, and disability," he writes.

"The combination of these multiple risks and the ALLHAT-LLT data showing that statin therapy in older adults may be associated with an increased mortality rate should be considered before prescribing or continuing statins for patients in this age category."

Is There a "Point of No Return"?

"It takes decades for the plaque to build up in the arteries that eventually causes strokes and heart attacks. Data from thousands of adults studied in clinical trials show us that statins, when started early, can interrupt or slow down that process," according to Navar.

But, "we don't know if there is a 'point of no return' where it's too late to start a statin, and ALLHAT was not designed to answer that question. We need a large randomized trial to really know how effective statins are when started in older adults without cardiovascular disease," she said.

"There is a lot of negative press about statins, and I really worry about the effect of studies like these on the public's perception. This study was a secondary analysis of a trial that was not designed to study the effect of statins in older adults," Navar observed.

"Data from thousands of adults in multiple randomized trials have shown that statins prevent heart disease and do not kill people. I hope that the media, in the never-ending search for clickbait, doesn't overemphasize the statistically nonsignificant mortality trend and lead people who are known to benefit to discontinue their statins."

The study was funded by the National Heart Lung & Blood Institute. Study medications were contributed by Pfizer, AstraZeneca, and Bristol-Myers Squibb, and financial support was provided by Pfizer. The study authors and Curfman report no relevant financial relationships. Navar reported research support from the National Institutes of Health, Amgen, and Sanofi & Regeneron Pharmaceuticals and serving as a consultant for Amgen and Sanofi.
Read the full article here.

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease - Gibson

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease


C. Michael Gibson MD‏           

 

Proud to be co-author of this New England Journal Med article showing lowering LDL does not always improve outcomes

Background

The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease.

Conclusions

Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease.

 (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998.)


Read the complete article here.

It’s official, statins do not have any side effects - Kendrick

It’s official, statins do not have any side effects

"The reality is, that unless you have had a previous heart attack, statins have no effect on overall mortality. To put that another way, they don’t save lives. They don’t even prevent heart attacks or strokes in women with no previous history of heart disease.

The statistic you really want to know about statins is the following. If you have had a heart attack, or stroke, and take a statin for five years, you will increase your life expectancy by 4.2 days. Balance that against a twenty per cent chance of having side effects, some of which are very unpleasant and long-lasting, and you can see why I am not a fan of statins."
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"A number of things were found. The most important of which, is just how many people stopped taking their statins after one year. A pretty staggering 75%. Why did they stop?

‘More than six in ten respondents (62%) said they discontinued their statin due to side effects, with the secondary factor (17%) being medication cost. Only 12% of respondents cited lack of efficacy in cholesterol management as a reason for stopping their medication. On average, respondents who experienced side effects due to their statin stopped after trying two different statins.

Three out of ten respondents experienced side effects of muscle pain and/or weakness, and 34% stopped taking their statin because of these side effects without consulting with their doctor.'

Read the complete article by Dr Kendrick here.

How much longer will you live if you take a statin?

"Looking at the Heart Protection Study (HPS) done in the UK, we used a technique for analysing survival time called RMST (restricted mean survival time). I won’t go into the details. The HPS study lasted for five years, and we calculated that the average increase in survival time was 15.6 days. This was at the end of five years of treatment (with a confidence interval of 5 days either side). For 4S, the figure was 17 days."

"Framing this slightly differently, what this meant was that taking a statin for one year, in the highest risk group possible, would increase your life expectancy by around three days."

"However, more recently the BMJ did decided to publish another paper entitled: ‘The effect of statins on average survival in randomised trials, an analysis of end point postponement.’

Results: 6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between −5 and 19 days in primary prevention trials and between −10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively."

Conclusions: Statin treatment results in a surprisingly small average gain in overall survival within the trials’ running time. For patients whose life expectancy is limited or who have adverse effects of treatment, withholding statin therapy should be considered

Overall their findings were far less impressive, even, than ours. They calculated, approximately, a single day of increase in life expectancy for each year of taking a statin. Slightly more in secondary prevention, slightly less in primary (people who have not previously had a heart attack or a stroke).

The main take away message I believe, is the following. Statins do not prevent fatal heart attacks and strokes. They can only delay them. They delay them by about one or two days per year of treatment. For those who have read my books you will know that I have regularly suggested we get rid of the concept of ‘preventative medicine’. We need to replace it with the concept of ‘delayative medicine’.

Read Dr. Kendrick's complete article here.

The effect of statins on average survival in randomised trials, an analysis of end point postponement

1. Malene Lopez Kristensen, 
2. Palle Mark Christensen, 
3. Jesper Hallas
5. Objective To estimate the average postponement of death in statin trials.
6. Primary outcome measures The average postponement of death as represented by the area between the survival curves.
   Results 6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between −5 and 19 days in primary prevention trials and between −10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively.
7. Conclusions Statin treatment results in a surprisingly small average gain in overall survival within the trials’ running time. For patients whose life expectancy is limited or who have adverse effects of treatment, withholding statin therapy should be considered.

Strengths and limitations of this study

• This is the first study ever to systematically evaluate statin trials using average postponement of death as the primary outcome.
• We have only estimated the survival gain achieved within the trials’ running time, whereas in real life, treatment is often continued much longer.
• We have only focused on all-cause mortality. Other outcomes may also be relevant, for example, non-fatal cardiovascular end points.

Read the complete article here.