The ACC meetings in New Orleans have wrapped up and I must stop letting the good times roll.
In the areas I paid attention to I found these four presentations the most important:
1. After the historic back to back presentations of the Partner 3 and Evolut trials it is clear that catheter-based aortic valve replacement (TAVR) should be the preferred approach to most patients with severe symptomatic aortic stenosis.
Both TAVR valves (the baloon-expanded Edwards and the self-expanding Medtronic) proved superior to surgical AVR in terms of one year clinical outcomes.
2. The Alcohol-AF Trial. It is well known that binge alcohol consumption (holiday heart) can trigger atrial fibrillation (AF) and that observational studies show a higher incident of AF with higher amounts of alcohol consumption.
This trial was the first ever randomized controlled trial of alcohol abstinence in moderate drinkers with paroxysmal AF (minimum 2 episodes in the last 6 months) or persistent AF requiring cardioversion.
Participants consumed >/= 10 standard drinks per week and were randomized to abstinence or usual consumption.
They underwent comprehensive rhythm monitoring with implantable loop recorders or existing pacemakers and twice daily AliveCor monitoring for 6 months.
Abstinence prolonged AF-free survival by 37% (118 vs 86 days) and lowered the AF burden from 8.2% to 5.6%
AF related hospitalizations occurred in 9% of abstinence patients versus 20% of controls
Those in the abstinence arm also experienced improved symptom severity, weight loss and BP control.
This trial gives me precise numbers to present to my AF patients to show them how important eliminating alcohol consumption is if they want to have less AF episodes.
It further emphasizes the point that lifestyle changes (including weight loss, exercise and stress-reduction) can dramatically reduce the incidence of atrial fibrillation.
Apixaban (Eliquis, one of the four newer oral anticoagulants (NOAC)) versus warfarin for patients with AF: which is safer for prevention of stroke related to AF?
Triple therapy with low dose aspirin and clopidogrel plus warfarin/NOAC versus clopidogrel plus warfarin/NOAC: which is safer in preventing stent thrombosis without causing excess bleeding in patients with AF and recent stent?
Briefly, they found:
The NOAC apixaban patients compared to warfarin had a 31% reduction in bleeding and hospitalization. No difference in ischemic events.
Adding aspirin increased bleeding by 89%. There was no difference in ischemic events. (Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001).)
This means that the dreaded “triple therapy” after PCI in patients with AF with its huge bleeding risks no longer is needed.
It also further emphasizes that NOACs should be preferred over warfarin in most patients with AF.
The combination of choice now should be a NOAC like apixaban plus clopidogrel.
4. REDUCE-IT provided further evidence that icosapent ethyl (Vascepa) significantly reduces major cardiovascular events in patients with establshed CV disease on maximally tolerated statin therapy.
The results of the pirmary end point from the REDUCE-IT were presented at the AHA meeting last year and they were very persuasive. At the ACC, Deepak Bhatt presented data on reduction of total ischemic events from the study and they were equally impressive. Adding the pharmaceutical grade esterified form of EPA at 2 grams BID reduced first, second, third and fourth ischemic events in this high risk population.
The benefit was noted on all terciles of baseline triglyceride levels. Thus, the lowest tercile of 81 to 190 mg/dl benefitted as well as the highest tercile (250 to 1401).
Although I dread the costs, it’s time to start discussing adding Vascepa on to statin therapy in high risk ASCVD patients who have trigs>100 .
As I wrote previously I didn’t learn anything from the much ballyhooed and highly anticipated Apple Heart Study . It’s entirely possible more participants were harmed than helped by this study.
Three years ago after hearing two amazing presentations at the ACC meeting the skeptical cardiologist opined:
These studies suggest to me for the first time that TAVR may ultimately replace SAVR for all patients with severe aortic stenosis, low to high in their risk for surgery.
Clearly, we need ongoing follow up of these patients and more long term data, but as these devices improve and the operators gain more experience it is likely that results will only get better.
This represents a huge paradigm shift in our approach to valvular heart disease.
This morning I watched two more amazing study presentations at the ACC meeting in New Orleans which unequivocally establish the minimally invasive TAVR procedure (which my cardiology colleagues perform here at St. Luke’s) as the treatment of choice for patients who have symptoms related to severe narrowing of their aortic valve (aortic stenosis).
I just published a piece on the presentations for the physician social media site, SERMO which follows:
Since 2015 it’s been clear to me that catheter-based procedures (TAVR) were a better option than open-heart surgical aortic valve replacement for most of my patients with severe symptomatic aortic stenosis who were at high (>8% STS ) and intermediate (>4% STS) risk for surgery.
Based on continued durability of TAVR results and outstanding results in my own institution, I’ve been advising my low risk patients with severe aortic stenosis that it was only a matter of time before TAVR would become the best option for them.
At the American College of Cardiology Meetings in New Orleans this morning two back to back presentations have confirmed that TAVR should be considered the treatment of choice rather than surgical aortic valve replacement ( SAVR) for most low risk patients with severe symptomatic AS.
This is such a dramatic paradigm shift in the treatment of AS that the Eugene Braunwald (now 90 years old) the first discussant of the presentations after reviewing the history of the treatment of AS, described it as an “historic moment” , one that we will tell our grandchildren that we were present at.
Furthermore, in a display I’ve never seen at an ACC session, the audience spontaneously stood and gave the presenters a standing ovation.
Both studies were published yesterday in the NEJM (something the presenters indicated was an error) and disappointingly I read the results described in a New York Times article prior to watching the live presentation.
The first presentation was from Martin Leon on the Partner 3 trial which utilizes the Edwards Sapien 3, third generation baloon-expandable valve. The study randomized 1,000 patients to either TAVR or standard SAVR with a bioprosthetic valve. The primary endpoint was the composite of death from any cause, stroke or re-hospitalization at one year after the procedure. At one year, the primary endpoint occurred in 8.5 percent of the TAVR group compared with 15.1 percent of the surgery group, meeting the requirements for both noninferiority (p<0.001) and superiority of TAVR vs. surgery (p<0.001).
The Kaplan-Meir analysis of the primary endpoint components with TAVR vs. surgery found mortality rates of 1.0 percent vs. 2.5 percent, stroke rates of 1.2 percent vs. 3.1 percent, and rehospitalization rates of 7.3 percent vs. 11.0 percent, respectively. The length of hospital stay was reduced from seven to three days with TAVR.
A cardiac surgeon, Michael Reardon (who I described as cocky and folksy in my 2015 post on TAVR), presented the results of the EVOLUT trial which randomized 1,468 patients to TAVR with a self-expanding bioprosthesis compared with surgical replacement. The primary endpoint was the composite of death from any cause or disabling stroke at 24 months. At 24 months, death or disabling stroke occurred in 5.3 percent of the TAVR group compared with 6.7 percent of the surgery group,
At 30 days, TAVR was statistically superior to surgery for the secondary combined endpoint of all-cause mortality or disabling stroke (0.8 vs. 2.6 percent). Patients receiving TAVR had significantly better quality of life and hemodynamics at 30 days.
I concur that these studies represent tremendous data that will drive a paradigm shift in the treatment of AS and anticipate that we will rapidly receive approval to use these two TAVR devices in all patients who meet the entry criteria (note that bicuspid AV was an exclusion but a subsequent presentation at ACC19 suggests that outcomes are similar in bicuspid valve patients to tricuspid valve patients).
The results of the Apple Heart Study, were presented this morning at the American College of Cardiology Scientific Sessions amid intense media scrutiny. The AHS is a “prospective, single arm pragmatic study” which had the primary objective of measuring the proportion of participants with an irregular pulse detected by the Apple Watch who turn out to have atrial fibrillation on subsequent ambulatory ECG patch monitoring.
I and over 400,000 other Apple Watch owners participated in the AH study by downloading the Apple Heart Study app and self-verifying our eligibility.
My assessment is that we have learned little to nothing from the AHS that we didn’t already know. I’m also concerned that many patients suffered anxiety or unnecessary testing after being referred to urgent care centers, emergency departments, cardiologists or primary care providers and the results of these inappropriate referrals may never be determined.
Here is the study in a nutshell:
Participants enrolled by submitting information using the iPhone Heart Study app and none of their isubmitted nformation was verified.
An irregular pulse notification was issued to 0.5% of participants who were then contacted and asked to participate in a Telehealth visit with a doctor (who we will call Dr. Appleseed)
Only 945 of the 2161 who received a pulse notification participated in the first study visit.
Interestingly, Dr. Appleseed was empowered to send participants to the ER if they had symptoms (chest pain, shortness of breath, fainting/losing consciousness) It is not clear how many were sent to the ER and what their outcomes were but this flow diagram shows that 20 were excluded from further testing due to “emergent symptoms.”
Another 174 participants were excluded after finding out at the first visit that they had a history of afib or aflutter and 90 due to current anticoagulant use (both of these factors were exclusion criteria which gives us an idea of how accurate the information was at the time of participant entry.)
After all these exclusions only 658 ECG monitor patches were shipped to the participants of which only 450 were returned and analyzed.
This means of the original 2161 participants who were notified of pulse irregularity, the study only reports data on 450 or 21%. Such a low rate of participation makes any conclusions from the study suspect.
Of the 450 ECG patches analyzed only 34% were classified as having afib. Only 25% of this afib lasted longer than 24 hours.
After the patch data was analyzed, patients had a second Telehealth visit with Dr. Appleseed who reviewed the findings with the patient. Per the initial published description of the methods of the AHS (see here) Dr. Appleseed would tell the participant to head to the ER if certain abnormalities were found on the ECG.
Per the study description (apple heart study), Dr. Appleseed recommended a visit to the PCP for “AF or any other arrhythmia” detected by the patch:”
“If AF or any other arrhythmias have been detected in reviewing the ambulatory ECG monitor data, or if there are other non-urgent symptom identified by the study physician during the video visit that may need further clinical evaluation, the Study Telehealth Provider directs the participant to his or her primary health care provider”
At this point it seems likely that a lot of participants were instructed to go see their PCPs. Because as someone who looks at a lot of 2 week ambulatory ECG recordings I know that is the rare recording that does not show “other arrhythmias.”
Even more distressing is the call that participants would have received based on “the initial technical read:” I’m presuming this “technical read” was by a technician and not by a cardiologist. In my experience, many initial reads from long term monitors are inaccurate.
“If the initial technical read identifies abnormalities that require urgent attention (ventricular tachycardia or ventricular fibrillation, high-degree heart block, long pauses, or sustained and very rapid ventricular rates), then the participant is contacted immediately and directed to local emergency care or advised how to seek local emergency care.”
I wonder how many ERs had AHS participants show up saying they had been told they had a life-threatening arrhythmia? How much down stream testing with possible invasive, life-threatening procedures such as cardiac catheterization were performed in response to these notifications?
Overall, these findings add nothing to previous studies using wearable PPG technology and they certainly don’t leave me with any confidence that the Apple Watch is accurately automatically detecting atrial fibrillation.
Was more harm than good done by the Apple Heart Study?
We will never know. The strength of this study, the large number of easily recruited participants is also its Achilles heel. We don’t know that any information about the participants is correct and we don’t have any validated follow up of the outcomes. In particular, I’m concerned that we don’t know what happened to all of these individuals who were sent to various health care providers thinking there might be something seriously wrong.
Perhaps Apple and Stanford need to review the first dictum of medicine: Primum Non Nocere, First Do No Harm.
Coronary artery calcium (CAC) scans are an excellent tool for better defining coronary heart disease risk in many individuals. In light of the recent ACC/AHA guidelines endorsement of CAC, the skeptical cardiologist anticipates that primary care physicians will be ordering more and will often be faced with the question of what to do with abnormally high results.
There are two, diametrically opposed viewpoints which have been taken on this issue.
The Argument For Stress Testing
The majority of cardiologists are likely to fall into the camp of “more testing is good” which was summarized in a State of The Art article that Dr. Harvey Hecht wrote in JACC recently.
The argument appears logical and is as follows:
There is a high yield of abnormal results from stress testing when done on patients with high CAC.
The appropriateness of stress testing after CAC scanning in asymptomatic patients is directly related to the CAC score. The incidence of abnormal nuclear stress testing is 1.3%, 11.3%, and 35.2% for CAC scores 400, respectively .
2. The higher yield for ischemia/abnormal tests in patients with >400 CAC implies the ability to further risk stratify patients thus leading to guideline recommendations:
It is only in the >400 group that the pretest likelihood is sufficiently high to warrant further evaluation with myocardial perfusion imaging, for which there is a IIb recommendation
Hecht references a 2010 guideline issued by ACC/AHA (2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults) which states
1. Stress myocardial perfusion imaging (MPI) may be considered for advanced cardiovascular risk assessment in asymptomatic adults with diabetes or asymptomatic adults with a strong family history of CHD or when previous risk assessment testing suggests a high risk of CHD, such as a coronary artery calcium (CAC) score of 400 or greater. (Level of Evidence: C)
Stress MPI testing is more sensitive than stress ECG testing alone but in clinical practice I see a very high rate of false positive stress MPI results. Stress MPI is also much more expensive than stress ECG testing and delivers significant radiation exposure to patients.
Thus if stress MPI is performed on all individuals with CAC>400 we are likely to generate lots of abnormal tests followed by lots of unnecessary down-stream testing.
Below is the incredibly complicated chart summarizing what tests can follow another abnormal test. Interestingly, in this chart the report consider it appropriate (A) to perform stress tests on individuals with calcium scores >100
Stress Testing-Costs and Downsides
The cynic in me has to point out that the average CAC score for white males of 67 years is 98 and that of 68 years is 115. Thus, this algorithm has the potential to recommend stress testing be performed on half of all white males with no symptoms over the age of 67.
The costs of this approach would be astronomical.
This guideline supports stress ECG, stress MPI and stress echo as appropriate. Stress MPI is considerably more expensive than stress ECG and carries substantial radiation burden. Stress echo in my experience, if performed and read properly has the lowest incidence of false positives and is more appropriate therefore for screening asymptomatic individuals.
All this stress testing stands to benefit the various members of the alphabet soup above, especially those who read nuclear stress tests or stress echo or who do catheterizations with stents. (Full disclosure I am board certified in nuclear cardiology and echocardiography and read both stress MPI and stress echos. I don’t do catheterizations.)
It’s also important to point out that these appropriate usage criteria, with rare exceptions are based primarily on the expert opinion of the stakeholders who stand to benefit from the additional testing.
The unspoken third leg of the argument for stress testing is that once an abnormal stress test is found and the patient is noted to be in a higher risk category for events, therapy will be changed and this therapeutic intervention will improve outcomes.
This therapeutic intervention could be more intense management of risk factors for CAD but in most cardiologist’s and patient’s minds the next step is coronary angiography with the potential to stent blocked coronaries or to perform coronary bypass surgery.
Diabetic Patients With High CAC
Asymptomatic individuals with diabetes are recognized as intrinsically higher risk for cardiac events and commonly do not experience symptoms even with advanced CAD.
Thus, they are often the focus of more intense screening recommendations.
In 2017, The Imaging Council of the American College of Cardiology published their review of evidence regarding the use of noninvasive testing to stratify asymptomatic patients with diabetes with regard to to coronary heart disease, ultimately coming up with the algorithm below.
Their arguments were similar to Hecht’s for the general population:
Asymptomatic patients with diabetes who have high CAC scores have a high prevalence of inducible ischemia on stress imaging. In a prospective study, 48% of patients with diabetes with a CAC score of 400 had silent ischemia on SPECT imaging, and in those with a score of 1000, 71.4% had inducible ischemia . The majority of the defects were moderate to severe. Patients with diabetes with inducible ischemia have a higher annual death
Despite higher rates of ischemic stress test results in diabetics they did not recommend stress testing for all:
the data in DM suggest that routine screening with MPI of all asymptomatic patients is likely to have a low yield and have a limited effect on patient outcome. The yield of MPI can be improved by selecting a higher-risk group of patients with symptoms, peripheral vascular disease, CKD, an abnormal ECG, or a high CAC score (e.g., >400) (83,84). In such patients, intense medical therapy appears to retard progression of asymptomatic and symptomatic CAD (72).
Importantly, they noted the absence of evidence for revascularization in this population:
Whether coronary revascularization offers additive prognostic benefit to medical therapy when the ischemic burden exceeds any particular threshold is still unclear for the asymptomatic diabetic population.
The Argument Against Stress Testing
The argument for stress testing for high CAC rests on the assumption that identifying those individuals with significant ischemia due to tightly blocked coronary arteries can improve outcomes. This hypothesis has never been tested, let alone proven.
It may seem logical that those asymptomatic individuals with high risk CAC scores >400 and ischemia would benefit from an invasive strategy with coronary angiography followed by either stenting or bypass surgery but it is entirely possible that such an invasive strategy could cause more harm than good.
Harm comes from subjecting those individuals with abnormal stress tests to a potentially lethal procedure-cardiac catheterization.
David Schade, an endocrinologist, has opined persuasively on the inadvisability of either stress testing or cardiology referral in those with high CACS.
He correctly points out the limitations of coronary angiography which some cardiologists are very eager to perform
In many locations, stress testing is performed after referring the asymptomatic patient to a cardiologist. After a positive stress test, the next step is usually coronary angiography to identify obstructive lesions. A recent review of coronary angiography recommends caution in the use of this test because (1) the resolution of coronary angiography is low; (2) the obtained images are two dimensional, making it difficult to define the shape of the vessel; and (3) the assessment of obstruction does not include the presence of previously developed collateral vessels, which may provide adequate blood flow past the obstruction
He quotes the USPSTF on the possible harm of this approach:
And he correctly points out that since the 2007 publication of the COURAGE trial we have known that catheterization followed by stenting does not improve outcomes in patients with stable CAD
Accord to the US Preventive Services Task Force: “The primary tangible harm of screening exercise tolerance testing is the potential for medical complications related to cardiac catheterization done to further evaluate a positive result. Coronary angiography is generally considered a safe procedure. Of all persons undergoing outpatient coronary angiography, however, an estimated 0.08% will die as a result of the procedure and 1.8% will experience a complication. Complications of coronary angiography include myocardial infarction, stroke, arrhythmia, dissection of the aorta and coronary artery, retroperitoneal bleeding, femoral artery aneurysm, renal dysfunction, and systemic infection”
In many locations, stress testing is performed after referring the asymptomatic patient to a cardiologist. After a positive stress test, the next step is usually coronary angiography to identify obstructive lesions. A recent review of coronary angiography recommends caution in the use of this test because (1) the resolution of coronary angiography is low; (2) the obtained images are two dimensional, making it difficult to define the shape of the vessel; and (3) the assessment of obstruction does not include the presence of previously developed collateral vessels, which may provide adequate blood flow past the obstruction
Schade’s algorithm for management of a high CAC specifically recommends against referral to a cardiologist or performance of a stress test.
It emphasizes very intense management of risk factors with lifestyle changes and medical therapy with LDL goal <70.
As a cardiologist with a strong interest in prevention of atherosclerosis I agree with many of Schade’s points. I do, however, believe that high risk patients can benefit from seeing a cardiologist who is very focused on prevention of atherosclotic complications rather than performing procedures.
I don’t routinely recommend stress testing for my patients with high CAC but I have a low threshold for recommending stress testing in them based on worrisome symptoms, especially in those who are more sedentary or are diabetic.
A randomized trial comparing the outcomes of stress testing versus aggressive optimal medical therapy for the asymptomatic individual with high CAC is sorely needed. Until then, I remain
The skeptical cardiologist recently prescribed ezetimibe to a patient who was leery of taking statin drugs for her elevated cholesterol. In the past she had taken red yeast rice in the belief that this was a safe and natural way to lower her cholesterol. I told her that I had looked into and researched red yeast rice (and wrote about it here), and that it was neither safe nor effective.
When I saw her back at our next office visit, she informed me that she had done her own research. She had gone on the internet and Googled ezetimibe and based on its “reviews” she felt it was an unsafe and dangerous drug.
It occurred to me at that point that patients like Ms X may actually believe that they can get reliable information on drug side effects and efficacy by going to a website where patients leave reviews on drugs they have taken.
Yelp For Medications
Such sites would be the equivalent of Yelp, which the wife of the skeptical cardiologist utilizes extensively to determine which restaurants we should patronize.
Lo and behold, if one Googles “reviews Zetia” a whole host of websites pop up offering you the opinions of random individuals on the drug.
On Everday Health Zetia gets 2 stars from 34 reviews with the most recent review being quite negative;
I hadRated Zetia for Rheumatoid Arthritis Report BEWARE. My husband took Zetia along with stantin, Crestor. Within a week, his leg muscles inflamed and shut down his kidneys and liver. He has been in the hospital for over a month and his condition has not improved. He’s on dialysis and can not walk. He is an alcoholic and his liver failed with Zetia.
Low dose of Zetia ….After just first days had severe diarrhea, halfed the dose. After a month I started seeing flashes in my right eye. Lots of eye fatigue, now a lot of ‘floaters’ in my right eye. Got checked by eye doctor to make sure it wasn’t optical nerve damage. Scarey. Coincidence? Don’t think so.
Limitations of The Yelp Concept In Assessing Medications
I empathize with and totally respect my patient’s desire to do her own independent research on the potential side effects of a drug that she will be putting in her body.
However, the Yelp approach just does not work well for medications.
There are three problems with relying on these kinds of patient-reported medication side effects.
The first is that the patients who leave comments on these sites are not representative of the overall pool of patients receiving the drug. Patients who feel they have been harmed in some significant way are much more likely to be motivated to spend the time recording what happened to them than are the individuals who felt fine after taking the drug.
There were 4 million prescriptions for ezetimibe written in 2015 and the number of patients leaving comments on these patient-review websites at most number in the hundreds. Thus, 99.9% of those taking ezetimibe are being silent, most likely because they are doing fine with the drug.
Secondly, most of the side effects reported by patients after taking ezetimibe occur at about the same frequency in those who take a placebo.
Although the package insert for ezetimibe lists various “common” side effects of the drug (such as diarrhea and upper respiratory infection), this table from the same package insert shows that such ailments are about as common in the group taking placebo.
The manufacturer, following FDA guidelines, reports out adverse reactions that are more common than 2% and numerically greater than placebo, but these are not necessarily significant differences.
Thus, we see that 4.1% of patients taking Zetia had diarrhea, but also that 3.7% of patients taking placebo had diarrhea.
If you take any group of several thousand individuals and follow them for a couple of months, probably 4% will get diarrhea whether or not they are taking ezetimibe.
The Nocebo Effect
Finally, we have to take into account the nocebo effect. The opposite of the placebo effect, in which inert substances make patients feel better, the nocebo effect makes patients who believe a drug will have side effects much more likely to experience those side effects.
The nocebo effect is quite common in patients who have read very negative comments on the internet about statin side effects. It is clear to me that this statin-related nocebo effect has also influenced patients taking non-statin cholesterol lowering medications like ezetimibe.
This is such an important factor in how patient’s tolerate ezetimibe that I spend considerable time during office visits emphasizing that ezetimibe works in a totally different way than statins, and is not associated with muscle aches/myalgias.
Alas, my patient has chosen to rely on the Yelp approach to deciding which medications to take. I’ve given her the best information I could on the safety and efficacy of ezetimibe based on my years of prescribing it and studying it. At this point it is her decision to make, and I accept it and we move forward managing her cardiovascular disease with the other tools in my toolkit.
Unlike an inaccurate restaurant review, however, a single individual describing inaccurately horrific side effects of a medication has the potential to steer thousands of patients away from potentially life-saving therapy.
In a previous post the skeptical cardiologist wrote about the reluctance of doctors to “heed the call” , i.e., to respond to an in-flight medical emergency (IME) when the flight crew requests assistance from qualified medical professionals.
Only 20% of physicians in my (very unscientific) poll would respond to such requests.
I pointed out that:
“In 1998 Congress passed the Aviation Medical Assistance Act, which tries to protect medical Good Samaritans who heed an airplane call. The act protects physicians, nurses, physician assistants, state-qualified EMTs and paramedics:
“An individual shall not be liable for damages in any action brought in a Federal or State court arising out of the acts or omissions of the individual in providing or attempting to provide assistance in the case of an in-flight medical emergency unless the individual, while rendering such assistance, is guilty of gross negligence or willful misconduct.”
but I and other physicians had concerns beyond medical liability, as I detailed in my post.
Physicians Who Prefer Not To Head The Call
At the time I wrote that piece, to be honest, I was in the camp of physicians who would prefer not to heed the call.
I tended to agree with Dr. Winocour on Larry David’s Curb Your Enthusiasm who justifies his failure to respond in flight with two comments:
“Give it a minute. He’s gonna be fine.” and
“Have you ever been part of an emergency landing? Is that what you want, Larry? To spend the night in Lubbock, Texas, at a Days Inn with a $15 voucher from Cinnabon? Think about it.”
Although Winocour was correct that the vast majority of in-flight medical “emergencies” resolve without any specific intervention it is still helpful for a physician to attend on such patients and assess the situation.
And it is true that if he had attended on a patient with a serious non-transient medical problem he would suddenly find himself having to make an incredibly difficult and life-deciding decision on whether or not to divert the plane or make an emergency landing with insufficient diagnostic tools and inadequate information.
But somebody has to make that call and the physician heeding the call will have the assistance of experts in the field on the ground.
Qualified Physicians Should Be Prepared To Heed The Call!
In fact, I am currently writing this while en route from frigid and
snowy St. Louis to sunny and warm San Diego on a Southwest Airlines flight and I’m considering pre-identifying myself as a physician in case an IME develops. (The only thing stopping me is that it seems a little pretentious and likely unnecessary, perhaps if I just put wear my stethoscope constantly that will be enough.)
I have in my backpack several items that will assist me in handling cardiovascular emergencies should they arise:
AliveCor Mobile ECG-With this and my iPhone I will be able to rapidly ascertain the stricken passengers heart rate and rhythm-crucial information to help diagnosis and proper treatment. (I also have my Apple Watch 4 for the same purpose.)
Stethoscope-a good one with which I can hear heart murmurs and lung sounds. Although the FAA-mandated emergency medical kit on board should have both a BP cuff and a stethoscope , I have no confidence they will be either accurate or functional.
Sublingual nitroglycerin. The kit on the plane should have these along with 325 mg aspirin tablets, IV atropine, and injectable glucose, epinephrine and lidocaine.
An epinephrine auto-injector. For the stricken passenger who is suffering anaphylaxis from the mixed nuts being served across the aisle.
Should there actually be a cardiac arrest I’m completely up to date on Advanced Cardiac Life Support (ACLS) and CPR training and there should be an AED on board to defibrillate if appropriate.
I’ve also decided that despite my reluctance to bring attention to myself, it is highly likely that I will be the most qualified person to rapidly diagnose and treat any serious cardiovascular condition that arises on my flight. As a doctor, I believe, I should be striving to provide assistance to those suffering whenever and wherever I can, be that in the air, on the sea, in the hospital or in the office.
N.B. One (of many) of the newly-minted wife’s favorite Airplane! lines comes from the doctor who heeded the call.
Rumack : You’d better tell the Captain we’ve got to land as soon as we can. This woman has to be gotten to a hospital.
Previously, the skeptical cardiologist described a patient with atrial fibrillation who was taking the blood thinner apixaban (Eliquis ) and developed a nose bleed after consuming a large amount of grapefruit (see here.)
In researching the whole subject of grapefruit-drug interactions I came across a fascinating intellectual battle between David Bailey, the researcher who first identified a significant grapefruit-drug interaction, and clinicians and researchers, some of whom are supported by the Florida Citrus Board, who feel this interaction is not significant.
What Does The Internet Tell Us?
It’s always interesting to see what patients doing a Google search will see on important medical topics. When I Googled “grapefruit Eliquis interaction” I saw the following:
The first item is an ad from the company that makes Eliquis which takes you to their patient-oriented Eliquis site and immediately presents you with important patient safety information. Nowhere on the site is the word grapefruit listed (as of July, 2018).
The second item is what Google calls a snippet and which they will present to you as what they think is the best answer to your Google search question. In this case the snippet (and the first 4 hits) is lifted from Web MD an absolutely unreliable source of information (see my post on entitled Web Md:Purveyor of bad health information and snake oil) but one which Google (and thus millions of unsuspecting Googlers) relies on for answers to medical questions . Web MD advises you to avoid grapefruit if you’re taking eliquis.
Close inspection of the WebMD article proffering this advice reveals the sole reference that actually bears on this topic: (Bailey et al , 2012 , CMAJ).
David Bailey: Rapid Runner and Grapefruit Alarmist
David Bailey may be better known as the first Canadian to run a mile in under 4 minutes. His Wikipedia entry spends equal time on his running career and on his major claim to fame: grapefruit drug interactions (GDI).
Bailey serendipitously discovered that grapefruit increased levels of the antihypertensive drug felodipine in his own body in 1987, information which was pretty much ignored until he published a research paper in the Lancet in 1991 showing a doubling of felodipine levels in 6 volunteers who consumed grapefruit.
Since then studies have shown that grapefruit juice acts by reducing presystemic felodipine metabolism through selective post-translational down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall.
Bailey has taken the grapefruit (and Seville orange) ball and run with it. His publications emphasize the broad scope and potential dangers of multiple grapefruit-drug interactions. A 2012 Bailey paper lists 85 drugs with the potential to interact with grapefruit juice including, you guessed it, apixaban.
Despite these potential interactions the actual number of clinically significant interactions or harm reported is minuscule. This has not deterred Bailey from emphasizing the importance of the interaction he discovered.
“The bottom line is that even if the frequency is low, the consequences can be dire,” he said. “Why do we have to have a body count before we make changes?”
“For 43 of the 85 drugs now on the list, consumption with grapefruit can be life-threatening, “
Articles, like the NY Times article typically buy into Bailey’s fear-mongering and spend multiple paragraphs describing a single case report suggesting that ingestion of grapefruit juice was responsible for a dangerous interaction but such cases are rare and strong evidence that grapefruit juice was responsible is not present.
What Can We Learn From The Florida Department of Citrus?
In fact, in a letter to the editor in response to Bailey’s 2012 review, two researchers point out that their is little solid evidence to suggest that the grapefruit-drug interactions are important
We know of no validated evidence that coadministration of grapefruit juice with a drug has caused a dangerous interaction, resulting in serious adverse effects or actual harm to a patient’s health. We point readers to 2 extensive review articles on grapefruit juice–drug interactions that have appeared in peer-reviewed medical literature.2,3 These articles provide a review of primary research literature, a compilation of the extent of interactions with specific drugs, and an evaluation of their clinical importance; however, neither of these publications is cited in the CMAJ article.
Whereas David Bailey has a bias to promote and exaggerate an interaction that is his claim to scientific fame most of the research and reviews that counter his claims come from researchers who are likely heavily biased to minimize the importance of the interaction: they are funded by the Florida Department of Citrus.
Are We Missing Important Grapefruit Medication Interactions?
David Bailey would like us to believe that the GFDI he identified in 1998 is hugely important. If only doctors would spend more time investigating the grapefruit consumption of their patients we would realize this. He writes
But how big a problem are such interactions? Unless health care professionals are aware of the possibility that the adverse event they are seeing might have an origin in the recent addition of grapefruit to the patient’s diet, it is very unlikely that they will investigate it. In addition, the patient may not volunteer this information. Thus, we contend that there remains a lack of knowledge about this interaction in the general health care community. Consequently, current data are not available to provide an absolute or even approximate number representing the true incidence of grapefruit–drug interactions in routine practiceThe chemicals in grapefruit involved in this interaction are the furanocoumarins.7
Bailey, goes on to warn us that all forms of grapefruit consumption can lead to dangerous interactions and other citrus fruits are to be feared as well
Because these chemicals are innate to grapefruit, all forms of the fruit (freshly squeezed juice, frozen concentrate and whole fruit) have the potential to reduce the activity of CYP3A4. One whole grapefruit or 200 mL of grapefruit juice is sufficient to cause clinically relevant increased systemic drug concentration and subsequent adverse effects.11,12 Seville oranges, (often used in marmalades), limes and pomelos also produce this interaction.13–15 Varieties of sweet orange, such as navel or valencia, do not contain furanocoumarins and do not produce this interaction.2
You can follow his references but they are not to patients who were harmed by grapefruit-drug interactions. Indeed, I am unaware of any of my patients reporting such harm until my patient with the nose bleed. I tend to agree with this unbiased editorial from BMJ in 2013
In our experience, and in that of our experienced colleagues, we have yet to come across clinically meaningful interactions of drugs and GFJ. This is despite our day to day experience of managing patients on statins, calcium channel antagonists, anti-platelet agents and anti-arrhythmics, which covers over 10,000 patients in the last 10 years alone. Likewise, there is little formal evidence of an impact, even from large scale clinical trials, with adjudicated and well documented endpoints.
After considerable research and communication with Pfizer, the maker of Eliquis, I ended up agreeing with Pfizer’s conclusion that the grapefruit-Eliquis interaction was unlikely to be significant:
When consumed in usual dietary volumes, grapefruit juice is considered a moderate inhibitor of CYP3A4. Therefore a dose adjustment of apixaban is not expected to be required.
CBD Oil, Grapefruit And Drug Interactions
I was reminded of the grapefruit-drug interaction in the last few weeks as several of my patients have started using CBD oil for various problems and have asked if it is safe to use with their cardiac medications.
I haven’t fully researched the CBD oil-drug interaction but the top Google search (“grapefruit and CBD oil”) result (from CBD school) states the following:
CBD interacts with other medications in your body in the same way as grapefruit, only even stronger.
However, the site that CBD school references (Project CBD) is not that definitive about grapefruit-drug interactions being a guide to CBD-grapefruit interactions.
And a recent scholarly article on the topic (see here) concludes
The drug-drug interactions between cannabinoids and various drugs at the CYP level are reported, but their clinical relevance remains unclear.
Which sounds very similar to where we are at with grapefruit-drug interactions in general.
I had my patient perform an experiment to see if the grapefruit actually caused her nose bleed. She repeated her consumption of large amounts of grapefruit and had no nosebleed this time.
The Oura ring is a novel, multisensory device that claims to be able to distinguish sleep stages, including REM sleep,. I purchased one recently and after several months of evaluation and an extensive look at the data supporting it I have to say I am much more impressed with OURA’s hype, marketing and style than any useful or actionable information about sleep that comes from it.
The Oura website is full of pictures of cool people doing cool things wearing their Oura rings-like this guy
It’s also chock full of marketing blather which implies that somehow the ring will dramatically improve your sleep and your waking life.
We see every individual as unique: your state of health and wellness today, tomorrow, and days to follow. Getting enough restorative sleep has a profound impact on mental and physical health and performance. Your daily choices and rhythms define how well you sleep. With Oura, you learn your optimal times to move, eat and take a break to get that restorative sleep. Giving you actionable steps to improve your life opens a totally new universe of possibilities – be it for mental, cognitive or physical performance, or for beauty, health, and longevity.
A quick look at the OURA web site certainly conveys the sense that this is the slickest, most cutting edge personal wearable sleep and activity tracker one could purchase.
However, despite Oura’s tantalizing claims there is only one legitimate scientific comparison of the ring to the gold-standard of sleep evaluation, polysmnography (PSG). This was published in 2017 in Behavior Sleep Medicine and its full contents can be read here.
In addition, there is no published evidence whatsoever that changing one’s behaviour based on the various parameters that the ring produces will have any favorable effect on your sleep quality or health in general.
I’ll be quoting from that 2017 published paper which I think is a good, unbiased analysis and I’ll throw in some of my own observations throughout this piece.
How The Ring Works And What It Claims To Do
A good night’s sleep, everyone should know by now is incredibly important to optimal performance the next day. In addition poor sleep quality is linked to a whole host of pathologies (with causality yet to be proven for most.) Thus, I quickly purchased an OURAring after hearing Peter Attia rave about his ring.
OURA likes to promote the idea that it has some sort of special way of measuring sleep based on a combination of sensors.
The Oura ring and its proprietary algorithms are a combination of extensive scientific understanding, years of careful research and development work, and top-notch engineering. All insights and guidance you get are based on proven algorithms and verified knowledge. For example, Oura’s sleep staging algorithms were the first in the market that have been independently validated. The validation study was made by SRI International.
The OURA website notes that the ring is fitted with the following sensors to collect physiologic signals from your body.
NTC BODY TEMPERATURE SENSOR The Oura ring registers your body temperature reading every minute while you sleep. By comparing that value to values from earlier nights, it indicates your body temperature baseline and any variations from it.
INFRARED LEDS Measuring blood volume pulse directly from the palmar arteries of the finger.
3D ACCELEROMETER AND GYROSCOPE Detects the amplitude and intensity of your body movement, automatically recognizes that you’re active and tracks the time you were inactive during the day.
Ōuraring (Oulu, Finland) claims to use these physiological signals (a combination of motion, heart rate, heart rate variability, and pulse wave variability amplitude) in combination with sophisticated machine learning based methods to calculate deep (PSG N3), light (PSG N1+N2) and rapid-eye-movement (REM) sleep in addition to sleep/wake states.
After obtaining a sizing kit from OURA I selected my ring and within a few weeks it was delivered. I downloaded the free OURA iPhone app, charged the ring with the supplied USB charger, slipped it on my left ring finger and eagerly awaited my first night’s analysis.
Upon arising in the morning I opened the OURA app and visualized an entrancing display like the one below.
It’s a nice graphic summary of the night’s sleep with my minutes of REM, light, and deep sleep nicely quantified.
More graphs and more data are available by connecting to Oura’s online application which automatically syncs to your smartphone app.
Unfortunately, the app was telling me that I was awake for 109 minutes of the time I was in bed. Which was not correct. I was truly awake only for 10 minutes around 130 AM. This overestimation of my awake time has been a consistent error of the ring for my recordings. If the app can’t accurately track awake time all of its metrics are going to be inaccurate.
In fact, over several months of using the ring/app I have found little relationship between how I feel after sleeping versus how Oura has rated my sleep. There is even less correlation between the “readiness” score that Oura produces and how I feel during the day. Overall, I have found absolutely no actionable information from my months of using the ring.
One morning Oura gave me a “readiness” score of 68 and told me:
“Don’t push it. Your resting heart rate was above average, so you might not be fully recovered”
I felt great throughout the day. These recommendations in my experience are almost unversally inaccurate and useless.
Oura also makes recommendations on when it thinks you should go to bed. One time it told me I should go to bed at 7 PM. I have been ignoring its advice in this area.
Now I am just one individual and it is entirely possible there is something unique about my sleep that invalidates the ring’s accuracy. The ex-eternal fiancee’ tells me I’m a restless sleeper.
In fact, devices that rely on actigraphy tend to be fairly accurate at identifying when you are sleeping but not when you are awake which is the opposite of what OURA is doing in my case.
The SRI paper puts it this way
Compared to PSG, actigraphy has high sensitivity (ability to detect sleep) although specificity (ability to detect wakefulness) is lower(Marino et al., 2013; Sadeh, 2011), with a wide range of accuracy,depending on the amount of night-time wakefulness(Paquet, Kawinska, & Carrier, 2007),the algorithms used and the particular population studied(Van de Water, Holmes, & Hurley, 2011). Most importantly, actigraphy relies on a single sensor, an accelerometer, and thus it provides a measure of motion from which it predicts sleep and wake states. However, information about sleep stage composition, fundamental in studying sleep and sleep disorders,is not provided.
The Science Behind Oura’s Sleep Analytics: Detecting Sleep Stages
So what does the SRI paper OURA likes to quote as proving its accuracy say.
The paper is entitled “The Sleep of the Ring: Comparison of the ŌURASleep TrackerAgainst Polysomnography” and it was written by researchers at SRI international, a research consortium in Menlo Park, California with no ties to OURA.
Another paper which used to be touted on the Oura Ring website (but is no longer referenced on the site) utilized home PSG recordings and was done by an in-house OURA employee.
The SRI researchers studied 41 healthy adolescents and young adults with an average of 17 years and sleep data were recorded using the ŌURA ring and standard PSG on a single laboratory overnight. Metrics were compared using Bland-Altman plots and epoch-by-epoch (EBE) analysis.
EBE analysis showed that ŌURA accurately detected “light” and “deep” sleep in 65% and 51% of the epochs, respectively. It also accurately detected REM sleep epochs 61% of the time, with an overall overestimationof PSG REM sleep (by about 17 min). When the ŌURA ring misclassified PSG REM sleep, the algorithm classified the epoch as “light sleep” (76%) for the majority of the time.
These data suggest that the Oura Ring is virtually useless in telling you if you are in REM sleep versus deep or light sleep.
As the authors noted
Distinguishing sleep stages such as REM and N3 with non-EEG based systems has been challenging and is a goal of several commercial sleep-trackers, with mixed success.
Clearly, further work is needed to determine what combination of sensors might be used to optimally develop an algorithm that differentiates sleep stages sufficiently well to detect real differences or changes in healthy and clinical populations.
A look at the Bland-Altman plots really tells you how much variation there was in the PSG estimates of various parameters versus the OURA
The Bland-Altman plots show us how much the PSG time in REM differed from the Oura REM time for each individual subject. You can see that some individuals had considerable over-estimation of REM time whereas other had considerable overestimation of REM time.
Although OURA REM time was on average only 17 minutes higher than the PSG REM time this was because the marked overestimation of REM time in some (7 subjects over 30 minutes) was balanced by marked underestimation in others (9 subjects with over 40 minutes and one with 160 minutes).
Given that the average REM time was 92 minutes for most subjects there was a significant discrepancy between PSG. and OURA assessments.
OURA: Coin Flip For Detecting Awake
Oura ring was also pretty useless at identifying when you are awake
Overall, ŌURA had 96% sensitivity (ability to detect sleep), 48% specificity (ability to detect wake), 65% agreementin detecting “light sleep”, 51% agreementin detecting “deep sleep”, and 61% agreementin detecting REM sleep, relative to PSG
Like other sleep sensors utilizing actigraphy, Oura in most individuals can’t accurately differentiate between times when you are lying still but awake and when you are lying still and asleep.
The limitations of wrist actigraphy (see here) for differentiating sleep from wake are worse in those with insomnia:
With actigraphy, because sleep is inferred from lack of movement, subjects who are awake but lie motionless can be classified incorrectly as being asleep, and thus the technique is biased toward overestimating time to sleep, which may lead to incorrectly minimizing the severity of sleep disturbances. This may present a specific challenge for patients with insomnia, and may partially explain the limited validity of wrist actigraphy for estimating sleep onset latency..
There are multiple other issues and questions with the usefulness of the data that Oura provides that need clarifying before the ring can be considered useful.
For example the SRI paper found significant differences in results depending on which finger the ring was placed on.
Interestingly, we found that PSG-ŌURA discrepancies for “light sleep” and REM were greater on the ring finger compared to the other fingers, a result that was independent from the amount of PSG sleep fragmentation.Assuming that the main parameters that ŌURA uses to determine sleep stages are motion and optical sensor outputs, it is possible that the different blood supply among fingers maypartially explain these results. For example, it has been shown that SpO2 values differ between fingers as well as hands suggesting a finger-dependent difference in accuracy of the pulse oximetry signal (Basaranoglu et al., 2015).Further studies should confirm and better characterize the dependency of the PSG-ŌURA discrepancies on the ring position by having the same participants simultaneously wear different rings on different fingers.
The in-house Oura study also noted that results were more accurate on the non-dominant hand finger compared to the dominant hand but the Oura website makes no recommendation on which finger to use.
The other data that Oura compiles (heart rate, heart rate variability, temperature change, respirations) are clearly related to sleep cycles but Oura provides no evidence that these data or their proprietary algorithms to give you “readiness” or sleep quality scores are accurate or of any value.
Shold You Buy An Oura Ring?
If you are hoping to get improved analysis of your sleep quality I don’t think Oura adds anything to what is elsewhere available using cheaper wrist actigraphy devices.
The ring is expensive at 299$ and cannot accurately detect sleep stages.
Although most reviews you will encounter on the internet are wildly enthusiastic about Oura, they are likely biased and they provide no evidence that the unique aspects of the ring sensors provide useful information.
Would I buy it again?
I’ve misplaced my ring several times and I have to say that this distressed me immensely. Given that I think the sleep analysis is worthless this is hard to explain.
I think my attachment to the ring is due to a number of factors
It’s stylish and it mimics a wedding ring (which I otherwise would not have.)
I’m intrigued by some of the cardiovascular data it produces (night time heart rate and heart rate variability). Although currently I don’t think the data can guide me to healthier behavior, it’s possible that there is useful information in there somewhere. I hope to write a post on heart rate variability down the line. I’ve done research in this area and have some strong opinions on its value.
I’m curious to see if the respiratory rate data and the temperature data is of any value whatsoever.
So, the ring is best I would say for well-heeled,, self-hacking and self-experimenting techno geeks.
The skeptical cardiologist recognizes that perhaps 10% of patients he starts on a statin drug will develop symptoms that are felt to be due to the drug.
Most often the symptom is myalgia-muscle ache.
But other symptoms may develop after the patient starts the drug and given widespread statin fear-mongering on the internet it is common for these symptoms to be attributed to the statin.
Recently a reader left comments on my post on statins and memory problems describing in detail what appears to be a statin side effect:
My doctor had me on a daily 40mg Lipitor. After about 1 month, I noticed that my short term memory was very bad*. (Not a nocebo effect… I had no idea at the time that statins were linked to memory effects.) I did an experiment on myself. I suspected that my memory problems were the result of the statin. (Nothing else seemed to be different besides the fact that I had started taking Lipitor the previous month.) After 2 weeks off of Lipitor, my memory problems went away. Whew. I put myself back on Lipitor (I didn’t want to die of a heart attack, and my “experiment” could have been a victim of confirmation bias + 100 other faults.) After about a month, crappy short term memory returned. Took myself off Lipitor again. AGAIN, after about 2 weeks, by memory was fine again.
Perhaps my experiment wasn’t scientific. Just one subject (me). 100% anecdotal. Perhaps statins are good for your heart. However, I don’t know about you, but I program computers for a living. Try doing that with crappy short term memory. Hint: you can’t do it.
I’ve outlined my approach to these potential statin associated symptoms (PSAS) previously (see here) and if a patient has resolution of the PSAS we typically try another statin to see if the PSAS recurs.
For my reader, it would make sense to try a statin like rosuvastatin or pitavastatin that is hydrophilic and therefore doesn’t cross the blood-brain barrier and enter the brain.
For the more common myalgias I typically try rosuvastatin at lower dosage. If symptoms recur on rosuvastatin I try pitavastatin.
Pitavastatin (Livalo) is the seventh statin. It is minimally affected by the cytochrome P450 system (meaning less drug-drug interactions), water soluble (so it doesn’t enter the brain,) and does not lower Co-enzyme Q10. These special biochemical characteristics raise the possibility that among patients who have not been able to tolerate other statins it might be both usable and efficacious.
It has been used in Japan since 2003 and was approved by the FDA for US use in 2010. The Medical Letter was pretty negative about it in 2010 and feels the same way about the recently approved zypitamag (pitavastatin magnesium.)
The Medical Letter’s review of pitavastatin calcium concluded that recommended doses of the drug had not been shown to decrease LDL-C more than other statins with longer safety records and there was no good reason to use it. That conclusion applies to pitavastatin magnesium as well.
Tom Dayspring, the “national treasure” and lipidologist disputes this and has written of the Medical Letter conclusions
Any statin that has been tested in an outcome trial has been successful and there is no reason why pitavastatin would not also reduce events. Most providers used every statin for years before there were outcomes! Pitavastatin was as successful in
regressing plaque volume as was atorvastatin in an IVUS trial called JAPAN-ACS ((J Am Coll Cardiol 2009;54:293–302). The claim regarding LDL lowering is erroneous as pitavastatin is actually more efficacious than fluvastatin, pravastatin, lovastatin, and 10 & 20 mg doses of simvastatin and the last sentence in the Medical Letter using the word “worrisome” is both ridiculous and 100% false – The pharmacokinetics of pitavastatin are extremely clean, better than all of the more lipophilic statins now on the market except fluvastatin (read the reference cited above which compares pitavastatin to all other statins using published data not invective). I cannot remember the last branded drug that was not first in its class to be released that the Medical Letter found any use for including Crestor which is why personally I find little use whatsoever for recommendations of the medical letter.
The Medical Letter does provide a nice summary of statins effectiveness and cost. As you can see Livalo (and any brand name statin) costs a lot more than generic rosuvastatin (276$ versus 8$) and is less effective
Thus, there is no reason to use any brand name statin unless you have developed side effects on two generic statins with the second one being low dose rosuvastatin.
Anecdotal Pitavastatin Success
Four years ago I identified by vascular screening in one of my patients, a 65 year old woman a >50% blockage in the left carotid artery.
We started her on 40 mg atorvastatin and she developed a rash. She was switched to rosuvastatin 10 mg and began waking up in the middle of the night with a headache and feeling light-headed. I thought it unlikely this symptom was due to the statin.
She requested that we go back to atorvastatin because she felt it likely the rash was from something else.one month later, complains of arms and legs are very sore and hard time getting dressed in the morning due to soreness. also constipated
We stopped the atorvastatin and a month later she called back indicating that she could feel her arteries clogging.
At this time we started Livalo at 2 mg twice weekly. LDL dropped by 50% to 71 mg/dl and she has tolerated it without side effects ever since.
Beyond anecdotal support for pitavastatin in the statin intolerant patient we have one abstract presented at the ACC meetings in 2013.
A total of 40 consecutive patients with documented intolerance to any dose of at least two different statins were prospectively enrolled into a protocol whereby they received a trial of pitavastatin therapy at a dose of 2 mg per day.
Forty patients were enrolled and 27 of them (68%) were able to tolerate pitavastatin. LDL cholesterol was reduced from 147±27 mg/dL to 93±25 mg/dL, resulting in an average LDL-cholesterol reduction of 34%. Patients who could best tolerate pitavastatin tended to be males and those with no history of coronary artery disease or diabetes.
Despite what the Medical Letter says about pitavastatin I tend to agree with Tom Dayspring and I and most progressive preventive cardiologists will give pitavastatin at least a trial in our high risk patients with PSAS before giving up on statins in them.
The Livalo website tries to hint that their drug might be better/safer for those of Japanese ethnicity but the science on this is not clear. A review on the topic concludes
Pharmacokinetic investigations have noted higher plasma levels of statins in Asians compared with Caucasians, although postmarketing data for all statins have not identified any particular safety issues, even when statins are given at equivalent doses. The potential mechanisms of heightened response to statins in Asians are related to genetically based differences in the metabolism of statins at the level of hepatic enzymes and drug transporters. Studies indicate that lower statin doses achieve lipid improvements in Asian patients comparable with those observed with higher doses in Caucasians. In conclusion, prescribing lower starting doses of statins in Asians appears warranted while research on this subject continues.