Statins & PCa Mortality

[pjoshea13]

New meta-analysis below.

About 11 years ago my doctor offered me a statin for my "high" cholesterol, which had just risen a little above 200.  I refused.  I felt that the case against cholesterol was simplistic & that a complex subject had been reduced to one villain - LDL cholesterol.

On Monday, I was amused to read of the failure of the Evacetrapib trial:

"... specialists were stunned by the results of a study of 12,000 patients, announced on Sunday at the American College of Cardiology’s annual meeting: There was no benefit from taking the drug, evacetrapib. The drug’s maker, Eli Lilly, stopped the study in October, citing futility, but it was not until Sunday’s meeting that cardiologists first saw the data behind that decision.

"Participants taking the drug saw their LDL levels fall to an average of 55 milligrams per deciliter from 84. Their HDL levels rose to an average of 104 milligram per deciliter from 46. Yet 256 participants had heart attacks, compared with 255 patients in the group who were taking a placebo."

“We had an agent that seemed to do all the right things,” said Dr. Stephen J. Nicholls, the study’s principal investigator and the deputy director of the South Australian Health and Medical Research Institute in Adelaide. “It’s the most mind-boggling question. How can a drug that lowers something that is associated with benefit not show any benefit?” he said ..."

“All of us would have put money on it,” said Dr. Peter Libby, a Harvard cardiologist. The drug, he said, “was the great hope.”

nytimes.com/2016/04/04/heal...

It would appear that Nicholls & Libby and all of the other stunned specialists have to rethink the ABCs of cholesterol & cardio health.  

In 2008, more than 50% of Americans aged 65-74 were using a statin, & the percentage was rising.  Presumably on the advice of the same specialists.

In the other corner, there are people like Mercola talking about the dire dangers of statins on their sites.

Anyway, leery of the appetite of PCa cells for cholesterol, I began using Simvastatin.  It's a bit awkward for a skeptic turned user to discuss the topic with men who seem to fear statins more than Lupron.  After all, there is something a little crazy about more than half the men my age needing to be on a statin.

But, regardless of what Dr. Mercola says, the PCa statistis are compelling.  In the new paper:

"In total, 13 studies that enrolled 100,536 participants were included in this meta-analysis."  

"Results showed that prediagnostic statin use had a significantly lower risk of both all-cause mortality {a 44% reduction}"

"and PCa-specific mortality {a 47% reduction}" 

"Similarly, postdiagnostic statin use was correlated with reductions in both {all-cause mortality - a 23% reduction}"

"and {PCa-specific mortality - a 36% reduction}"

-Patrick

ncbi.nlm.nih.gov/pubmed/270...

Onco Targets Ther. 2016 Mar 21;9:1689-1696.

Statin use and mortality of patients with prostate cancer: a meta-analysis.

Meng Y1, Liao YB2, Xu P1, Wei WR1, Wang J1.

Author information

Abstract

OBJECTIVE:

The aim of this meta-analysis was to investigate the effect of statin use on the mortality of patients with prostate cancer (PCa).

METHODS:

An electronic search of PubMed, Embase, and CENTRAL databases from inception to August 2015 was performed to find eligible studies. Articles investigating the association between statin use and mortality of PCa were identified. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models.

RESULTS:

In total, 13 studies that enrolled 100,536 participants were included in this meta-analysis. Results showed that prediagnostic statin use had a significantly lower risk of both all-cause mortality (ACM; HR, 0.56; 95% CI, 0.38-0.83) and PCa-specific mortality (PCSM; HR, 0.53; 95% CI, 0.36-0.77). Similarly, postdiagnostic statin use was correlated with reductions in both ACM (HR, 0.77; 95% CI, 0.69-0.87) and PCSM (HR, 0.64; 95% CI, 0.52-0.79). When stratified by primary treatment, postdiagnostic use of statins had a 0.4-fold lower risk of ACM in patients with PCa who were treated with local therapy; both pre- and postdiagnostic use of statins was correlated with a significantly lower risk of PCSM in patients who were treated with androgen deprivation therapy.

CONCLUSION:

Both pre- and postdiagnostic use of statins is associated with better overall survival and PCa-specific survival. This suggests a need for randomized controlled trials of statins in patients with PCa.

KEYWORDS:

all-cause mortality; prostate cancer; prostate cancer-specific mortality; statins

PMID: 27051303 [PubMed - as supplied by publisher]

[Dan59]

Pat,

Thanks for the great information!

Dan

[Neal-Snyder]

I'd been on Simvastatin (after another statin) for cholesterol for years before my PC diagnosis in 2003, & I still am. Of course I was delighted when I first read about the statins & PC study.

Maybe there are studies of other statins that show effectiveness in what they were designed for? 

[pjoshea13 in reply to Neal-Snyder]

Hi Neal,

I should have mentioned that evacetrapib is not a statin.  Its failure indicates that lowering LDL cholesterol, in itself, does not reduce CVD risk.  So we have to ask what statins might be doing in addition to reducing cholesterol.

One of my obsessions is the link between inflammation control & survival.  Even in disease-free people, inflammation markers correlate with 5-year mortality.  Some markers are a standard part of the panel included in an annual medical, & yet doctors never seem to discuss them.  Perhaps because the observed ranges are too wide, yet considered to be normal, or at least acceptable.

It turns out that statins have a beneficial effect on inflammation.  There are currently 85 PubMed hits where "statins" & "inflammation" appear in the paper's title.  Inevitably, studies that seek to associate cholesterol-lowering with survival, will be confounded by statins effects on inflammation.

Owens, 2012:

"During the past 2 decades, atherosclerosis and its clinical sequelae have increasingly been recognized as an inflammatory disease. Examination of multiple circulating inflammatory biomarkers has shown that they independently predict cardiovascular risk in patients with and without overt cardiovascular disease. Among these, high-sensitivity C-reactive protein has proved to be most robust in adding to global risk prediction models. Statins, a class of drugs that reduce levels of high-sensitivity C-reactive protein and other inflammatory biomarkers, have been the most thoroughly studied anti-inflammatory agents to reduce cardiovascular risk. However, all such trials are necessarily confounded by the ability of statins to markedly reduce cholesterol, a well-known causal risk factor for adverse vascular outcomes. Nevertheless, the provocative results of several key statin trials have provided the scientific basis to test the hypothesis that reducing inflammation will improve cardiovascular outcomes with novel and specific anti-inflammatory agents. These newer drugs promise to reduce inflammatory marker levels without affecting lipids, glucose, or blood pressure. The results of these trials will provide key data to help us understand the relationship between inflammation and vascular risk."

ncbi.nlm.nih.gov/pubmed/230...

From an interesting 2010 meta-analysis:

"Statins have been shown to reduce the risk of all-cause mortality among individuals with clinical history of coronary heart disease. However, it remains uncertain whether statins have similar mortality benefit in a high-risk primary prevention setting. Notably, all systematic reviews to date included trials that in part incorporated participants with prior cardiovascular disease (CVD) at baseline. Our objective was to reliably determine if statin therapy reduces all-cause mortality among intermediate to high-risk individuals without a history of CVD."

"Data were combined from 11 studies and effect estimates were pooled ... Data were available on 65,229 participants followed for approximately 244,000 person-years, during which 2793 deaths occurred."

"This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up."

ncbi.nlm.nih.gov/pubmed/205...

The statins/inflammation literature is awash with studies of conditions that seem unconnected with lipids.  e.g. this 2011 meta-analysis of patients with infection:

"Sixteen trials (11 retrospective and 5 prospective cohort studies) involving 8775 cases in statins group and 46 539 in control group were included for analysis. The mortalities of infection were 5.2% (458/8775) and 18.6% (8637/46,539) in statins and control groups respectively."

"Statins have favorable effects on the patients with infection, but there is no effect for severe septic patients in ICU."

ncbi.nlm.nih.gov/pubmed/220...

-Patrick