The 2013 Cochrane review of primary prevention with statins concluded that they reduce all cause mortality and cardiovascular events without increasing the risk of adverse events among people at low risk of cardiovascular disease (<10% over 10 years).1 However, just two years earlier, a Cochrane review had concluded that existing evidence did not support the use of cholesterol lowering statins for people with <20% 10 year cardiovascular risk: “Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.”2 This conclusion was consistent with the 2006-08 guidance from the National Institute for Health and Care Excellence (NICE)3 and the 2011 update of the American Heart Association’s guidelines for the prevention of cardiovascular disease in women, both of which recommended statin therapy only when the 10 year risk of disease is 20% or greater.4
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It concludes as follows that statins do more harm than good in people at low risk for cardiovascular events:
"Our calculations using data presented in the 2012 CTT patient level meta-analysis show that statin therapy prevents one serious cardiovascular event per 140 low risk people (five year risk <10%) treated for five years. Statin therapy in low risk people does not reduce all cause mortality or serious illness and has about an 18% risk of causing side effects that range from minor and reversible to serious and irreversible. Broadening the recommendations in cholesterol lowering guidelines to include statin therapy for low risk individuals will unnecessarily increase the incidence of adverse effects without providing overall health benefit."
"Our calculations using data presented in the 2012 CTT patient level meta-analysis show that statin therapy prevents one serious cardiovascular event per 140 low risk people (five year risk <10%) treated for five years. Statin therapy in low risk people does not reduce all cause mortality or serious illness and has about an 18% risk of causing side effects that range from minor and reversible to serious and irreversible. Broadening the recommendations in cholesterol lowering guidelines to include statin therapy for low risk individuals will unnecessarily increase the incidence of adverse effects without providing overall health benefit."
Question 1: Why do industry /pharm sponsored studies have higher success rates and lower side effects reporting than non biased studies?
Answer from study:
"A recent Cochrane review found that industry sponsored clinical trials are significantly more
likely than non-commercially funded studies to report favourable efficacy and safety results
and conclusions."
"” However,the large discrepancies between the frequency of adverse events reported in commercially funded randomized controlled trials included in CTT meta-analyses and on-commercially funded studies show that determination of harms cannot be left to industry alone"
Well that makes sense to me.
Next question:" So tell me again Doc, why i need to go on a Statin?" I consider the following study information that i am NOT told:
"Our calculations using data presented in the 2012 CTT patient level meta-analysis show that statin therapy prevents one serious cardiovascular event per 140 low risk
people (five year risk <10%) treated for five years. Statin therapy in low risk people
does not reduce all cause mortality or serious illness and has about an 18% risk of causing side effects that range from minor and reversible to serious and irreversible. "
So i can reduce my chances of a serious heart event in the next 5 years by UNDER 3/4of a percent. But i get the added risk of potentially serious and serious side effects that is nearly 25 times greater than the benefit? How does this make any sense at all?
Gee, why would i be put on a Statin? Perhaps the Docs MUST prescribe it or face serious professional sanctions or issues? Looks like they are, even those who don't like em..
"A recent Cochrane review found that industry sponsored clinical trials are significantly more
likely than non-commercially funded studies to report favourable efficacy and safety results
and conclusions."
"” However,the large discrepancies between the frequency of adverse events reported in commercially funded randomized controlled trials included in CTT meta-analyses and on-commercially funded studies show that determination of harms cannot be left to industry alone"
Well that makes sense to me.
Next question:" So tell me again Doc, why i need to go on a Statin?" I consider the following study information that i am NOT told:
"Our calculations using data presented in the 2012 CTT patient level meta-analysis show that statin therapy prevents one serious cardiovascular event per 140 low risk
people (five year risk <10%) treated for five years. Statin therapy in low risk people
does not reduce all cause mortality or serious illness and has about an 18% risk of causing side effects that range from minor and reversible to serious and irreversible. "
So i can reduce my chances of a serious heart event in the next 5 years by UNDER 3/4of a percent. But i get the added risk of potentially serious and serious side effects that is nearly 25 times greater than the benefit? How does this make any sense at all?
Gee, why would i be put on a Statin? Perhaps the Docs MUST prescribe it or face serious professional sanctions or issues? Looks like they are, even those who don't like em..
From study analysis:
"Rather than being compelled by guidelines to prescribe statin therapy for people at low risk of cardiovascular disease, doctors would provide a far greater service by explaining the magnitude of the benefits and uncertainty about the harms of statins together with discussion of the epidemiological evidence showing that behavioural risk factors—including
tobacco use, lack of physical exercise, and unhealthy diet—are responsible for 80% of
cardiovascular disease ."
BUT..................................
The conclusion and summary box of this Analysis article by Abramson and colleagues (BMJ 2013;347:f6123, doi:10.1136/bmj.f6123) stated that side effects of statins occur in about 18-20% of patients. The authors withdraw this statement.
Although it was based on statements in the referenced observational study by Zhang and colleagues, that “the rate of reported statin-related events to statins was nearly 18%,”1 the article did not reflect necessary caveats and did not take sufficient account of the uncontrolled nature of the study.
Zhang et al observed that the rate of statin related events found in their study (18%) was “substantially higher than the 5% to 10% usually described in randomized, placebo-controlled, clinical trials.” Two caveats must be considered. As Zhang et al point out, the rate of statin related events reported in their study was uncontrolled and therefore may be inflated because events attributed to statins might have occurred in a placebo group as well. In addition, although Zhang et al do not make this point, the 5-10% rate quoted by Zhang et al as having been observed in randomised trials was, in many cases, similar in both active and placebo groups.
The exact rate of statin related adverse events in people at low risk of cardiovascular disease remains uncertain. Clinical trials may underestimate the frequency of statin related adverse events because of patient selection, exclusion of older patients and those with comorbid conditions or potential drug interactions, under-representation of women, and selection bias created by willingness to participate in a clinical trial. In addition, when compared with the full clinical study reports, published accounts of clinical trials in medical journals report only a minority of adverse events.2 Access to the full data from the trials of statins would help to determine the comparative rates of serious adverse events in statin and control groups but probably would not help to determine the frequency of less than serious adverse events.
The authors also mistakenly reported that Zhang et al found that “18% of statin treated patients had discontinued therapy (at least temporarily) because of statin related events.” The correct interpretation of the data, as confirmed to The BMJ by Zhang et al, is as follows. Based on review of structured electronic medical record categories and automated review of unstructured narratives from follow-up visits of 107 835 patients over eight years, 18 778 of all study patients (17.4%) had a statin related event documented during the study. Among those who experienced a statin related event, only 59.2% had statin therapy discontinued at least temporarily. However, because of possible miscategorisation resulting from the limited options in the electronic medical record for recording reasons for discontinuation of statin therapy, Zhang et al concluded that “as many as 87%” of these discontinuations could have been due to statin-related events. This equates to up to 9% of the study population having possibly discontinued statin therapy as a consequence of statin related events, rather than the 18% cited.
The primary finding of Abramson and colleague’s article—that the Cholesterol Treatment Trialists’ data failed to show that statins reduced the overall risk of mortality among people with <20% risk of cardiovascular disease over the next 10 years—was not challenged in the process of communication about this correction.
Competing interests: John Abramson and Nicholas Jewell serve as experts in litigation involving the pharmaceutical and medical device industries, including a case involving a statin
Abramson et al.(1) question the benefit of statin therapy in low risk patients, as recommended by the new cholesterol treatment guidelines.(2)This conclusion is based on the author’s evaluation of a meta-analysis performed by the Cholesterol Treatment Trialists' (CTT) Collaborators.(3) First, Abramson et al.(1) state that in the setting of primary prevention statins have not been shown to have an impact on all-cause mortality. In the JUPITER trial 17,802 otherwise healthy participants were randomized to treatment with rosuvastatin 20 mg daily or placebo.(4) Over 97% of study participants had a 5 year risk of major vascular events (MVE) of less than 10%.(3) After a median follow-up of 1.9 years (maximum 5 years) rosuvastatin reduced the risk for all-cause mortality by 20% compared to placebo (HR 0.80, 95% CI 0.67-0.97, p=0.02). Furthermore, this reduction in mortality was seen after only a median follow-up of 1.9 years.(4)
In addition to the JUPITER study, two other trials conducted in predominantly low risk patient populations (AFCAPS/TexCAPS(5) and MEGA(6)) were included in the CTT meta-analysis that evaluated outcomes considered to be “serious adverse events” as defined by Abramson et al.(1) Over 95% of patients enrolled in these trials had an MVE of less than 10%.(3) In JUPITER, rosuvastatin reduced the rate of arterial vascularization or hospitalization for unstable angina (HR 0.53, 95% CI 0.4-0.7, p<0.00001).(4) In AFCAPS/TexCAPS, treatment with lovastatin 20-40 mg daily reduced the rate of coronary revascularizations (HR 0.67, 95% CI 0.52-0.85, p=0.001) and unstable angina (RR 0.68, 95% CI 0.49-0.95, p=0.02).(5) Finally, the MEGA trial showed that after an average follow-up of 5.3 years pravastatin 10-20 mg daily significantly reduced the risk for myocardial infarction and coronary revascularization (HR 0.52, 95% CI 0.29-0.94, p<0.03; HR 0.60 95% CI 0.41-0.89, p<0.01, respectively).(6) These studies also report no increased risk of fatal or non-fatal cancer or death from non-CV causes, further supporting the safety and efficacy of statin therapy in primary prevention.(4-6)
Lastly, the authors(1) state "Under the proposed 2013 standards…no level of risk would preclude statin therapy, raising the question of whether or not all people over the age of 50 should be treated." However, it is noted in the Guidelines that patients aged 40-75 years without clinical CHD (i.e. primary prevention therapy) with a baseline LDL of 70-189 mg/dL and an estimated 10-year risk greater than 7.5% should be considered for statin therapy. By specifying that the 10-year risk be elevated above 7.5% the guidelines note that not all patients over the age of 40 will be treated with a statin.(2) Furthermore, those patients with a 10 year risk below 5%, discussed extensively by Abramson et. al, (1) would be excluded from statin therapy.
Kyle A. Davis, Pharm.D, BCPS
Jackson Memorial Hospital
Miami USA
Jackson Memorial Hospital
Miami USA
Eric Dietrich, PharmD, BCPS
Department of Community Health and Family Medicine
University of Florida
Gainesville USA
Department of Community Health and Family Medicine
University of Florida
Gainesville USA
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