5 Steps to prevent Heart Disease

Friday, August 5, 2016

Guidelines choose drugs without head to head trials?

"In the absence of high quality head-to-head drug comparison trials to determine the relative efficacy of the individual drugs, choice of therapy should be based upon
1- efficacy,
2-safety,
3-cost, 
4-convenience,
5-and other patient-related factors [30,31]."

The above is from Up To Date on choosing drugs for Osteoporosis.



Below is criteria for choosing drugs from a Consensus Committee
 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk.

The process employed in the creation of the ECDP document was supported by the ACC without external funding - See more at: http://www.acc.org/latest-in-cardiology/articles/2016/04/07/14/32/a-consensus-approach-to-the-use-of-non-statin-therapy-for-atherosclerotic-cardiovascular-disease-prevention#sthash.cv2ZMPed.dpuf
 "The process employed in the creation of the ECDP document was supported by the ACC without external funding"

the value of patient-provider interaction in clinical decision making when non-statin therapies are considered, examining the extent of available scientific evidence for net clinical benefit, safety and tolerability, potential for drug-drug interactions, efficacy of additional LDL-C lowering, cost, convenience and medication storage, pill burden, route of administration, and patient preferences; - See more at: http://www.acc.org/latest-in-cardiology/articles/2016/04/07/14/32/a-consensus-approach-to-the-use-of-non-statin-therapy-for-atherosclerotic-cardiovascular-disease-prevention#sthash.cv2ZMPed.dpuf
"the value of patient-provider interaction in clinical decision making when non-statin therapies are considered,
1-examining the extent of available scientific evidence for net clinical benefit,
2- safety and
3- tolerability,
4- potential for drug-drug interactions,
5-efficacy of additional LDL-C lowering, 
6-cost, 
7-convenience and
8-medication storage,
9-pill burden,
10-route of administration, and
11-patient preference"


 NEJM article Head to Head trial

"As compared with ezetimibe, niacin had greater efficacy regarding the change in mean carotid intima–media thickness over 14 months (P=0.003), leading to significant reduction of both mean (P=0.001) and maximal carotid intima–media thickness
Paradoxically, greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima–media thickness (R=–0.31, P<0 .001="" p="">
Interestingly there are head to head trials with Niacin.
Most famous is the Coronary Drug Project 
in which
"Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004)" after 15 years.

Yet somehow Niacin failed to make the list of non-statin drugs allowed on the list yet PCSK9 which is $1,000 a month, has no outcome studies and is given intravenously is on the list?








Niacin was dropped from guidelines because of  AIM-HIGH and HPS-THRIVE were stopped early.


These were not LDLc lowering trials.  LDLc was already at goal with statins.
These were HDLc and triglyceride trials.

Why then are they used against Niacin in a guideline that has in its criteria:
5-"efficacy of additional LDL-C lowering," 

This is the result of Niacin's effect on LDLc in AIM-HIGH



"It took 7 years of follow-up for us to reach that many events, so some investigators were wondering if this would be the eternal trial," Cannon said. "But that was really good news because it meant that the treatment was working: we were actually doing good for our patients."
It should, however, be noted that 42% of patients, regardless of treatment, stopped the study drug before the end of the trial.

Zetia was added to the list by the consensus committee because it had the IMPROVE-IT positive outcome.

If AIM-HIGH went out to 7 years it may also have had a positive outcome.  It was a government study however.
There were some illnesses in patients on Niacin and AIM-HIGH was stopped early.  Later these illnesses were found not to be statistically significant but I believe it is the reason the committee left Niacin off the list of advised drugs. 







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