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mac_in_tosh

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I’m not sure what the number of pills has to do with anything. I would say a 1 in 60 difference is quite significant if you consider the tens of millions of people at risk and the consequences at hand.
The number of pills has to do with potential quality of life reduction due to side effects of taking statins over long periods of time, especially for the relatively large number of people getting no actual benefit from the drug. I'm curious, what is the threshold NNT to consider a drug to be ineffective? 200? 500? 1000?

Good for you for having a conservative approach toward prescribing medications.

By the way, are you familiar with this study?:

Kristensen ML, Christensen PM, Hallas J The effect of statins on average survival in randomised trials, an analysis of end point postponement BMJ Open 2015;5:e007118. doi: 10.1136/bmjopen-2014-007118

They concluded using data from six studies with 2-6 year followups that statins provided a median gain in overall survival of just a few days.
 

Herdfan

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Good for you for having a conservative approach toward prescribing medications.

We certainly need a lot more like that.

I am 56 and it sometimes seems that medical professionals don't believe the wife (57) and I when we say we don't take any prescription medications. I guess by our age you are really supposed to be on a handful and it just goes up from there.
 

Alli

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I’m looking forward to my onco taking me off letrozole in the fall. It’s responsible for all the other medications I’m taking, including a statin.
 

Roller

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We certainly need a lot more like that.

I am 56 and it sometimes seems that medical professionals don't believe the wife (57) and I when we say we don't take any prescription medications. I guess by our age you are really supposed to be on a handful and it just goes up from there.
Unfortunately, our healthcare system is geared toward treatment rather than prevention. And, as the song goes, "One pill makes you larger, and one pill makes you small, and the ones that mother gives you, don't do anything at all." That's not to minimize the value of drugs that save millions of lives, but I think it's led to unrealistic expectations and poor behaviors.

The pandemic has exacerbated the situation by fostering an atmosphere where questionable, worthless, or dangerous therapies receive as much attention as ones that have been shown to be effective.
 

Clix Pix

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We certainly need a lot more like that.

I am 56 and it sometimes seems that medical professionals don't believe the wife (57) and I when we say we don't take any prescription medications. I guess by our age you are really supposed to be on a handful and it just goes up from there.
I'm 77 and don't take any prescription meds, either; also rarely take anything OTC.
 

mac_in_tosh

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We certainly need a lot more like that.

I am 56 and it sometimes seems that medical professionals don't believe the wife (57) and I when we say we don't take any prescription medications. I guess by our age you are really supposed to be on a handful and it just goes up from there.
Finding some area of agreement with @Herdfan is upsetting. Is there a pill for that?
 

rdrr

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We certainly need a lot more like that.

I am 56 and it sometimes seems that medical professionals don't believe the wife (57) and I when we say we don't take any prescription medications. I guess by our age you are really supposed to be on a handful and it just goes up from there.
I am exactly you age (go Gen X), and I am currently on 3 pills and 2 supplements. There are only two pills for actual issues, high BP and cholesterol. The other 3 are Potassium, Vitamin D and Vitamin B12 are all due to the BP medicine. So I am their perfect customer... A middle aged individual taking pills, because they are taking pills. I do want to note that as of 3 years ago I have been on a "getting healthier" journey. I was on a beta blocker, and anti-Ds as well, but I am happy to say that I am off of those (with the guidance of a great doctor I found). Currently my goal is to get my weight down enough to get off of the BP, and I am down 36 pounds so far, with another 20 - 25 pounds to go. I am not sure if I will ever get off of the statin, because everyone on my Mom's side of the family and my brother all are on statins, and not all of that family is overweight.
 

AG_PhamD

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The number of pills has to do with potential quality of life reduction due to side effects of taking statins over long periods of time, especially for the relatively large number of people getting no actual benefit from the drug. I'm curious, what is the threshold NNT to consider a drug to be ineffective? 200? 500? 1000?

Good for you for having a conservative approach toward prescribing medications.

By the way, are you familiar with this study?:

Kristensen ML, Christensen PM, Hallas J The effect of statins on average survival in randomised trials, an analysis of end point postponement BMJ Open 2015;5:e007118. doi: 10.1136/bmjopen-2014-007118

They concluded using data from six studies with 2-6 year followups that statins provided a median gain in overall survival of just a few days.

The number of pills isn’t really relevant in this context. You seem to assume either the more pills taken or the longer medications are taken, the more likely an individual will experience adverse effects. There are some drugs where prolonged exposure risks cumulative side effects (ie steroids), but that is not really considered the case with statins. Adverse effects typically are apparent within a week. Many will subside within days.

In some cases, there are some benefits in taking drugs longer half lives, which effectively translates to the frequency the medication must be taken to maintain stable plasma concentrations. Off the top of my head all statins, at least the commonly used ones, are recommended to be dosed once a day. You could split up the dosing though.

I have not seen that study but I briefly looked over it. I would have to go through all the studies however to assess their quality, but I will assume for the most part they are good. I would point out these limitations/issues, some of which the author noted.
- This meta-analysis is limited to the timeframe of the studies selected (2-5 years), which may not demonstrate the true long term benefits, which are known to be apparent over the course of many years
- A lack of discussion on the inclusion/exclusion criteria of patients- this could be assessed by reading all the trials. But generally, what conditions excluded participants?
- There is no analysis of selection bias including the age distribution- are all the participants in their 50’s? Or 40+? Or 70+? Were any participants taking statins or other hyperlipidemia treatments prior?
- The study treats all patients of having uniform benefit (survival gain), not assessing what factors would influence like age, pre-existing conditions
- At least some of the studies state they had no mechanism of confirming med adherence (were they reliably taking the meds) or do not mention this. FYI Medication adherence in the general population is about 50%, often lower in select groups. Generally you need at least 80% for a drug to be effective.
- Only all-cause mortality was considered- so #1 we don’t know what caused the deaths (CV event or something totally unrelated) and #2 this does not assess the reduction in cardiovascular events ie heart attack and stroke.
(It’s worth noting heart attack and stroke victims have about a 90% and 80-90% chance of immediate survival, respectively… which is far better than in the past. That said, these events, especially stroke, can cause significant permanent disability)​
- The result of the study is a prediction based on a model, created using a rather limited set information. They reportedly also used scaled images of graphs and Microsoft Paint as an analytical tool. That doesn’t mean their analysis is wrong, but does make me question their resources.
- It’s an awfully short write up given the amount of data compared to other meta analyses, which I suppose is understandable given the limitations.

The authors own conclusion, understanding the analytical limitations, does not recommend not taking statins (and she even cites their benefits), but rather to be more flexible in patients who experience adverse effects and those with short life expectancies. I think that’s a reasonable conclusion and one that I already operate under.
We believe that statins should be prescribed according to the prevailing guidelines. Statins are usually inexpensive and safe, at least in a clinical trial setting,20 and the benefit in terms of mortality or non-fatal cardiovascular outcomes cannot reasonably be challenged. However, if the patient has intolerance or unpleasant side effects from statins, for example, muscular problems, physicians should not be too insistent on the patient continuing them. Also, for patients whose life expectancy is short, the benefit of statin therapy in terms of survival gain may be quite limited.21

Full Text: https://bmjopen.bmj.com/content/bmjopen/5/9/e007118.full.pdf

I do think this study raises an interesting question about gained survival benefit (especially in terms of quantifying benefit to patients which is part of the discussion of this paper) but this study is really not an adequate method to assess this. The problem is to look at this thoroughly, takes decades of follow up with participants which is very difficult, very costly, and obviously very time consuming. Looking at past medical records would be a more reasonable way of doing this in a timely manner, but has its own limitations, esp selection bias.

I don’t want to come off as condescending as that’s not my intention, but this why reading and analyzing studies beyond the results summary is important. You will even find some papers have abstracts and conclusions that really don’t align with their reported results. It’s important to challenge any study you read, regardless of where it’s published or your preconceived notions. And to know that every study has its limitations.
 

AG_PhamD

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We certainly need a lot more like that.

I am 56 and it sometimes seems that medical professionals don't believe the wife (57) and I when we say we don't take any prescription medications. I guess by our age you are really supposed to be on a handful and it just goes up from there.
Yeah, I think my record for the patient with the most Rx’s upon intake was 27 (twenty-seven). It was ridiculous. Most of it was redundant or completely unnecessary. And this patient was nearly not as unhealthy as you’d think with 27 prescriptions. It’s actually somewhat amazing she wasn’t dead from the drug interactions.

This overprescribing happens a lot, but is especially true of lpsych meds. These patients often bounce around from prescriber to prescriber (and/or facility to facility). It seems most prescribers don’t want to touch the psych meds, so if symptoms are not improving, they just add on more and don’t discontinue what’s not working.

Then with side effects, the solution rather than changing the dose or medication is another drug to treat the side effect, and then you start having the medication cascade of drugs treating side effects of drugs.
My mother is in her mid-60’s, a physician herself, and doesn’t take any medications. So it is entirely possible.

I’m looking forward to my onco taking me off letrozole in the fall. It’s responsible for all the other medications I’m taking, including a statin.
I assume that means you’ve been in remission for some time?

I’m not well versed in the intricacies of chemo/anti-cancer agents (I still have nightmares about my oncology rotation) but if I’m not mistaken the letrazole + statins (simvastatin?) combo is more effective at inhibiting cancer cells?

That's not to minimize the value of drugs that save millions of lives, but I think it's led to unrealistic expectations and poor behaviors.

Our society has a problem that they want easy, effortless solutions to often complex problems. A pre-diabetic patient is much more inclined to continue their less than desirable lifestyle options if they can fix their blood sugar by taking a pill vs making the lifestyle changes that could also ameliorate their condition.

There is also a problem where when many people go to the doctor for a specific ailment, they expect to be given some sort of medication (Again, looking an easy solution). But if they are not prescribed something, they feel short changed or that the provider isn’t doing his/her job. So then providers feel obligated to prescribe something just to appease the patient. It’s a bad cycle.

Antidepressants are a good example of false expectations- with patients, family members, and many prescribers (often PCP’s). That’s not to say antidepressants don’t have a place in treatment, they do, but they’re rarely the be-all-end-all, especially for sustainable recovery. Every study shows therapy in conjunction with antidepressants works best, yet 70% of people take antidepressants but don’t see a therapist*. That’s because depression is very much related to how people think of themselves and process life challenges.

*As you can imagine, access to therapy can be challenging for many due to cost, time, location, etc. But many people are prescribed without even the suggestion of therapy.
 

mac_in_tosh

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The number of pills isn’t really relevant in this context. You seem to assume either the more pills taken or the longer medications are taken, the more likely an individual will experience adverse effects. There are some drugs where prolonged exposure risks cumulative side effects (ie steroids), but that is not really considered the case with statins. Adverse effects typically are apparent within a week. Many will subside within days.
Thank you for taking the time to share your expertise. You may have missed one of my questions in a previous post. You introduced the concept of NNT in the discussion of statins and gave examples of 60 and 45 for two groups of people. I was curious as to what would be the threshold NNT to consider a drug to be ineffective or of marginal value?

In the American Heart Association item I showed, in a particular group of 100 people not taking statins 5 people will have a heart related incident in a six year period. If the 100 people took statins, that number is reduced to...not 0, not 1, not 2, not 3 but 4. The vast majority will receive no benefit and 2 will have side effects to varying degrees. Would that translate into a NNT of 100 for this specific group? Since the AHA was touting these results, I gather an NNT of even 100 is considered as showing a drug's effectiveness. How high is too high?
 

Herdfan

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Our society has a problem that they want easy, effortless solutions to often complex problems. A pre-diabetic patient is much more inclined to continue their less than desirable lifestyle options if they can fix their blood sugar by taking a pill vs making the lifestyle changes that could also ameliorate their condition.

So you've met my SIL. She simply takes more pills so she can continue to go to Starbucks every morning. :eek:

My mom was the same way. If there was a "pill for that", she was taking it so she didn't have to make changes. Had a Dr. actually tell her once if she did this and that, she could get off her scooter and she responded "why would I want to do that?" It was the bag of pills her and my dad were toting around that caused me to be more anti-pill than I probably should be.

I am exactly you age (go Gen X), and I am currently on 3 pills and 2 supplements. There are only two pills for actual issues, high BP and cholesterol. The other 3 are Potassium, Vitamin D and Vitamin B12 are all due to the BP medicine. So I am their perfect customer... A middle aged individual taking pills, because they are taking pills. I do want to note that as of 3 years ago I have been on a "getting healthier" journey. I was on a beta blocker, and anti-Ds as well, but I am happy to say that I am off of those (with the guidance of a great doctor I found). Currently my goal is to get my weight down enough to get off of the BP, and I am down 36 pounds so far, with another 20 - 25 pounds to go. I am not sure if I will ever get off of the statin, because everyone on my Mom's side of the family and my brother all are on statins, and not all of that family is overweight.

That's awesome. I have found there is a very simple way to lose weight. Eat less and move around more. It won't be quick, but it will be lasting.
 

mac_in_tosh

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My mom was the same way. If there was a "pill for that", she was taking it so she didn't have to make changes.
That type of behavior is at least partly explained by the avalanche of drug commercials on t.v. You got a problem? Talk to your doctor. He'll give you this pill and then you can be like the smiling people in the commercial (often moving in slow motion for some reason).

I don't know the current situation but as of a few years ago only the U.S. and New Zealand allowed drug commercials to be shown. And has been pointed out, it creates an expectation on the part of patients for a quick fix and many people think that the doctor isn't doing his job unless he writes out a prescription for something.
 

Herdfan

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I don't know the current situation but as of a few years ago only the U.S. and New Zealand allowed drug commercials to be shown.

I remember one drug company, although not which exact one, before the US relaxed their rules came up with a clever way around it.

Back then drug companies could advertise their drug, but not what it "cured" or advertise what it "cured", but not allowed to name the drug. It was always talk to your doctor.

So this company came out with 2 ads. One had a picture of the product with people doing activities. A second had the same exact people doing the same activities, yet it talked about a drug that could fix all that. It didn't long to pu the two together figure out what that drug did. Genius on their part.

As for commercials today, the list of side effects makes me not want to take any of them.
 

rdrr

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That's awesome. I have found there is a very simple way to lose weight. Eat less and move around more. It won't be quick, but it will be lasting.

That is what I am doing, but added one more cut out sweets.. the 30ish pounds that I have lost was over the past 9-10 months, slow and steady. I am on kind of a crunch timeline for the rest. I won't marry fat.

Got to talk to the doctor though about what a healthy BMI is, because according to the chart I should be 168 lbs, and not my current ideal weight. I don't think I have seen 168 since my freshman year at college, that seems too skinny to me.
 

Herdfan

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That is what I am doing, but added one more cut out sweets.. the 30ish pounds that I have lost was over the past 9-10 months, slow and steady. I am on kind of a crunch timeline for the rest. I won't marry fat.

Got to talk to the doctor though about what a healthy BMI is, because according to the chart I should be 168 lbs, and not my current ideal weight. I don't think I have seen 168 since my freshman year at college, that seems too skinny to me.

The sweets is a big one for sure. I eat almost no processed sugar anymore. I used to get either a bag of chips or Twinkies or a candy bar when I went into a c-store to get a drink. Now I just get the drink. If I am at a birthday party or something, sure I will eat some cake, but I just don't make sugar a part of my daily intake.

I think I would look emaciated at my ideal BMI.

Good luck!
 

mac_in_tosh

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So this company came out with 2 ads. One had a picture of the product with people doing activities. A second had the same exact people doing the same activities, yet it talked about a drug that could fix all that. It didn't long to pu the two together figure out what that drug did. Genius on their part.

As for commercials today, the list of side effects makes me not want to take any of them.
I didn't know that history but once in a while before a YouTube video starts there's a very short ad where the smiling speaker says that he talked to his doctor about ----. It never even mentions what the drug is for. Strange.

Maybe instead of the phrase "side effects," which is a bit of a euphemism, they should be called "harmful effects."

Despite @AG_PhamD's sincere efforts here, it will take a lot to overcome an innate suspicion when it comes to drug companies with all the money that's involved. Their history has been to bury unfavorable results, to have on their payroll government officials who make decisions about the safety of their products, to flood doctor offices with their reps and to direct market their products to the public, which I find shameful because they are appealing to possibly desperate people.
 

AG_PhamD

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Thank you for taking the time to share your expertise. You may have missed one of my questions in a previous post. You introduced the concept of NNT in the discussion of statins and gave examples of 60 and 45 for two groups of people. I was curious as to what would be the threshold NNT to consider a drug to be ineffective or of marginal value?

In the American Heart Association item I showed, in a particular group of 100 people not taking statins 5 people will have a heart related incident in a six year period. If the 100 people took statins, that number is reduced to...not 0, not 1, not 2, not 3 but 4. The vast majority will receive no benefit and 2 will have side effects to varying degrees. Would that translate into a NNT of 100 for this specific group? Since the AHA was touting these results, I gather an NNT of even 100 is considered as showing a drug's effectiveness. How high is too high?

My pleasure. I think these are important things to discuss.

NNT is a fairly involved topic to dig into, especially if we’re taking about medications used in primary prevention and health outcomes ideally measured on the scale of decades. Such is the case with stations and CV events.

The ideal NNT would be 1, meaning every patient treated has a benefit. The value of NNT in the real world is dependent on a lot of factors, like how serious outcome is of the potential condition you’re trying to prevent, the costs of that undesirable outcome (incl financial, effect on quality of living, productivity, etc), the potential side effects and risks of the intervention, the cost of the intervention, the benefits beyond preventing the condition, how prevalent the condition is, how well the undesired outcome can be treated if not prevented, what alternatives exist, etc. An epidemiology textbook might say 5-10 is generally ideal, but in reality considering an intervention’s value really depends on a multitude of factors beyond its clinical utility, including economic, social, etc.

NNT is also highly dependent on how studies are conducted, especially the what baseline risk of the participants is and how long the study was conducted. We know that statins benefit people at the highest risk who have been taking the medication the longest. So NNT is and will be skewed if relatively healthy young people with high cholesterol and high risk old people who just started taking statins late in life vs. people who are high risk who have been taking statins for many years. And a study over the course of 2 vs 5 vs 20 vs 40 years will likely demonstrate different results. So as it stands, many of the NNT’s are based off of a broad spectrum of patients over a short period. And it’s worth noting it can be difficult to predict what a 35 year old’s health situation will be in 30-40 years.

It should also be noted that statin guidelines have changed over time- at least several times in my career (depending on if you follow USPSTF or ACC/AHA guidelines). The USPSTF just came out with the newest guidance last year and in some respects are actually more conservative.

The treatment algorithms are based on an individually calculated ASCVD (atherosclerotic cardiovascular disease) risk score. This informs the chance of having a cardiac event in the next 10 years. The newest guidelines generally recommend initiating statins for those with an ASCVD score of 10%.

I won’t get into the technical definitions of side effect vs. adverse effect vs. adverse event. Side effects are predictable but unintended effects, usually undesirable (but in some cases can they can be beneficial). Adverse reactions are harmful effects caused when the drug is otherwise properly taken.

Regardless, to avoid being technical, not all side effects (in the vernacular sense) are harmful, but they may be tolerable or inconvenient. Or they may so intolerable in which case another of action needs to be considered.

Harm generally means causing substantial distress, physiological damage, or risk of death. Slight fatigue caused by a drug is not considered harm. Kidney damage would be.

It’s not like patients are forced to take medication and that prescribers ignore the experience of the patient. If a drug’s side effects are that bad, then they’re less likely to take it, and it defeats the entire purpose.

That said, the benefit of the drug is always weighed against the risks, including side effects. In the case of cancer and cytotoxic chemotherapy, there’s obviously terrible and debilitating side effects, but it’s a life or death situation. Thus most people, at least for some time, endure. If the condition is less serious, there’s going less of a tolerance for significant side effects.

It should also be mentioned there is often a false equivalency of potential benefit vs side effects. If they were in reality equal, no one would ever take any medication. The reduction in risk of a stroke isn’t comparable to a mild headache that subsides in 2 days.

Side effect statistics usually don’t take into consideration the severity of general adverse effects or how long they last or the cause ie adverse effects seen in the placebo groups are not subtracted and in many cases are the same or higher. Obviously however there are some side effects than are predictable and easily attributable to the mechanism of the drug.

———
Re: Pharmaceutical companies, there is always reason to be skeptical of their reporting given their conflict of interest. The government has cracked down significantly on companies hiding clinical data with much greater oversight. And given numerous controversies, it’s not surprising the public is skeptical. And I’m not telling you to inherently trust them.

The thing often forgotten is the government and research institutions (universities, hospitals) does their own independent studies. Statins in particular are generic and have a flooded market, so the original inventors are not really making any money anymore. After 30 years and billions of prescriptions, I think we have a pretty good understanding of what risks they pose. Measuring benefits as described above is much more complex to measure given a long list of significant variable discussed earlier.

I should also mention I think the impact of money on individual providers is vastly overestimated. It’s not like a couple+ decades ago where a pharma kickbacks were legal and everywhere.
 
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