Cardiovascular | DrPullen.com – Medical and Health Blog

Category Archives: Cardiovascular

Statin Side Effects: Add Type 2 Diabetes?

January 11, 2012 Dr. Pullen

Statin Side Effects: Add Type 2 Diabetes?

I want to weigh in briefly on all the headline news on the review in the online Archives of Internal Medicine about the increased incidence of type 2 diabetes in older women taking statins. In this analysis of the data from the Women’s Health Initiative an increase of about 50% in the incidence of new cases of diabetes was found in women taking a statin when compared to women not taking a statin. At first glance this sounds terrible. Giving people at high risk of cardiovascular disease a drug that increases their risk of developing diabetes when the leading cause of death in diabetic patients is cardiovascular disease may seem odd.

For me this is really a call to reason. I hear jokes about putting statins in the water supply as if they are a magic medication that patients really need a reason not to take. The bulk of the evidence is clear that statins are indeed a terrific class of medications. In patients with cardiovascular disease, and in patients at high risk of cardiovascular disease, statins have proven to reduce rates of death and cardiac events like heart attack and stroke in study after study. Still, even drugs with all the positive outcome data of the statins is not without risk. The potential for statin side effects especially myalgia are well-known. Now we can probably add an increased risk of developing diabetes to the long-term statin risks.

I suspect that when the dust settles on this issue we are going to continue to encourage the use of statins for patients with elevated LDL cholesterol when their whole profile of risks (looking at other factors like smoking, blood pressure and diabetes in addition to just their LDL cholesterol) puts them at high risk. I also suspect that we will become more circumspect about advising statins for patients with moderately high cholesterol and few other risks.

It looks like our water supplies are safe from added statins for the time being. We can probably add an increased risk of type 2 diabetes to the list of statin side effects.

See also: Simvastatin vs. Lipitor and Any Advantages or is Livalo Just One More Statin?

What do you think? - Leave a comment!

The Best Christmas Gift Ever

December 13, 2011 Dr. Pullen

Give Your Loved Ones The Best Christmas Gift Ever This Year!
Really. What your loved ones want most from you is for you to be healthy and around for them. This involves doing whatever you can to avoid the leading cause of death and morbidity in the U.S., cardiovascular disease like heart attack and stroke. The CDC has made this easy by making an electronic gift card available to send to those you love and who care about you. The card says:
My Health is my gift to you this holiday season. “I pledge to learn my ABCS of health,” and is associated with the Million Hearts Program of the CDC.
For those of you not familiar with the ABCS of the Million Hearts attempt to prevent 1,000,000 heart attacks and strokes in the 5 years following the initiative on Sept 13, 2011 it is:

Click on this Image to Go to the Million Hearts Site Now!

• A= Aspirin for those people at high risk. This generally means adults with high blood pressure, diabetes, any type of vascular disease like peripheral vascular disease, coronary disease, carotid disease etc, smokers, people with high cholesterol or high blood pressure, and those with a strong family history of heart attack or stroke.
• B= Blood Pressure Control: Sounds obvious, but less than half of Americans with high blood pressure have it adequately controlled. Don’t settle for suboptimal blood pressure control. Work with your doctor to do what it takes to gain control. Also focus on the non-medication things you can do like salt restriction, weight loss and more exercise.
• C= Cholesterol management: Goals vary for different people, but ask your physician what your goal cholesterol should be, and if needed use medication plus diet to get to that goal.
• S= Smoking Cessation: If you smoke quitting is probably the number one thing you can do to reduce your chances of a heart attack or stroke. People always correlate smoking with cancer and lung disease, but the leading way smoking kills is from cardiovascular diseases like heart attacks and stroke. Do whatever it takes to find a way to quit.
So this year give the most precious gift of all, yourself through improved health and longer life, to your loved ones.

What do you think? - Leave a comment!

Give a Gift on Black Friday

November 21, 2011 Dr. Pullen

Add Some Red to Black Friday and I’ll give some Green to the American Cancer Society

Millions of Americans shop for Christmas gift bargains on Black Friday every year. I encourage you to give a gift on Black Friday that costs you nothing more that a little time, and which can help you feel you have truly given life and hope during this holiday season.

My readers will know that I’m a big proponent of regular blood donations. Kay, my wife has ovarian cancer and has been a recipient of donated blood when her blood counts get low from chemotherapy. Cancer patients are among the highest users of donated blood products from red blood cells to platelets. I’m donating regularly to be sure our family puts more blood into the blood banking system than we take out. I want you to join with me on the Friday after Thanksgiving this year by paying a visit to your local blood donation center. There are even potential blood donation health benefits.

I’m putting out a challenge to readers, your friends and anyone else you can contact. Black Friday is a day when many of us are out and about shopping and getting ready for the holidays. The holiday season is also a time when blood donations tend to fall behind need. Here is the challenge:

I’ll donate $1. (up to $1000) for every comment to this post or tweet me @DoctorPullen telling me that you have or intend to go to your local blood donation center on Black Friday and donate blood. $1. may sound like chump change, but I want to get 1000+ people who would otherwise not donate blood to do so this Friday. We are in a world of easy communication, and I bet everyone who reads this knows 10 people who are in a position to get to their blood donation center this black Friday and donate. Just do it!

Take a break from shopping, get off your feet, and relax while you give one special holiday gift. Use the twitter or facebook links to send this off to your friends, tell your coworkers, shout from the roof tops, whatever but let’s make this Black Friday blood red with our generosity.

My daughter, son and I plan to go to the local Cascade Regional Blood Bank center in Puyallup Friday. I checked and they are open 7:30 AM – 5:00PM. I’ll try to keep a counter going on the site to let you all know how we are doing.

They Turned Me Away Today

Egg on my face. I went today to donate, but was turned away because I went to Belize on vacation a couple of months age, an area with malaria exposure potential. I’m now ineligible for a year, joining a majority of the rest of Americans. If you are among the 37% who are eligible donors get to your blood donation center and give. Keep our blood supply safe and plentiful. Happy Thanksgiving.

6 Comments - Leave a comment!

Why Quit Smoking?

November 17, 2011 Dr. Pullen

This post is in appreciation of the 35th anniversary of the first “Smokeout”, actually the November 18, 1976 “Don’t Smoke Day” (D-Day) in San Francisco sponsored by the California Division of the American Cancer Society which received national (all 3 major national networks at the time ) and became a national event thereafter. The third Thursday of November each year, just one week prior to Thanksgiving is the Great American Smokeout. About 45.8 million Americans still smoke and most studies show more American smokers would like to quit smoking than those who don’t want to quit. Here are some great reasons to quit:
1. Retire Early(or take a nice vacation every year) on the Savings: If you smoke 1 pack of cigarettes a day for a year, at an average cost in Washington State where I live and work at the average cost in WA of $9.89/ pack you spend $3609.85 a year on cigarettes alone. If saved the 3609.85 annually and invested it at only 4% you would have $111,794.17 in 20 years. It would be more if you invested daily or monthly. Quit smoking now and you can be a long way towards a retirement fund. You may also live to retire. (I admit Washington is the second most expensive state to buy cigarettes in the U.S.)
2. It Stinks: Any non-smoker can tell you that they can smell the odor of cigarettes on your clothing, hair and body from several feet away. By quitting smoking you will avoid smelling repulsive to the majority of others in society.
3. Live Longer and Better: The average smoker dies 7 years earlier than the average non-smoker, and estimates of the time lost per cigarette smoked is 7-10 minutes per cigarette. The whole issue is really much more complex that this, but without doubt quitting smoking can add significant time to the average person’s lifespan.
4. Better Sex for Longer: Smokers have a much higher incidence of peripheral vascular disease, and erectile dysfunction is often the result of vascular disease. Quitting smoking can lead to a better sex life for many smokers.
5. Dying of COPD is Among the Worst Ways to Die: This is my personal opinion, but I’ve taken care of people who have died nearly every common cause of death. Respiratory failure has to be among the least desirable way to die. Being essentially immobile, gasping for air while on oxygen for months or years, and finally dying of a respiratory infection that leads to inability to breath is not among the ways I hope to die.
6. Get Your Kids/Grandkids/Spouse/…. Off Your Case: Nearly every smoker I see in the office comments that their loved ones are hoping the get them to quit, and often annoying them with encouragement and pestering. Why not change all that to congratulations and positive reinforcement after you quit?
7. Feel Proud that You Quit: Most smokers would like to quit smoking. Most who do tell me that they are happy and proud that they were able to quit. Join the ranks of proud ex-smokers.
Please leave comment with more and better reasons to quit. I’d love to have this post be a place for smokers to find the right reason for them and quit themselves. There is no time like today!

Don’t miss a post. Subscribe using the right sidebar feature.

USPSTF C, D and I Screening Recommendations

September 14, 2011 Dr. Pullen

When Not to Do Screening Tests

An argument can be made that knowing when not to do screening for a disease or condition is as important as knowing when to do screening. The USPSTF makes recommendations to physicians and patients about what screening preventative services should be done in asymptomatic patients, and which should not be done routinely. The USPSTF is an evidence based decision making body. They carefully review the evidence and make recommendations for or against screening based solely on the available evidence which helps keep emotional and arbitrary recommendations from becoming the mandate. The recommendations are separated into 5 grades:

A Recommendation: The USPSTF recommends the service. There is high certainty that the net benefit is substantial.
B Recommendation: The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.
C Recommendation: The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.
D Recommendation: The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.
I Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

I thought it was timely to list a few of the screening services that the USPSTF recommends against, or finds insufficient evidence to make a recommendation for or against. This list is not intended to be comprehensive. See the USPSTF site for a complete list of their screening recommendations.
Cancer Screening Recommendations:

The USPSTF recommends against routine testicular cancer screening in adolescent and adult males. D recommendation.
The USPSTF recommends against routine ovarian cancer screening. D recommendation.
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of using a whole-body skin examination by a primary care clinician or patient skin self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population. I recommendation.
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of prostate cancer screening in men younger than age 75 years. I Recommendation.
The USPSTF recommends against screening for prostate cancer in men age 75 years or older. Grade: D Recommendation.
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for bladder cancer in asymptomatic adults. Grade: I Statement.

Heart and Vascular Disease Recommendations:

The U.S. Preventive Services Task Force (USPSTF) recommends against screening for asymptomatic carotid artery stenosis (CAS) in the general adult population. Grade: D Recommendation.
The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening with resting electrocardiography (ECG), exercise treadmill test (ETT), or electron-beam computerized tomography (EBCT) scanning for coronary calcium for either the presence of severe coronary artery stenosis (CAS) or the prediction of coronary heart disease (CHD) events in adults at low risk for CHD events. Grade: D Recommendation.
The USPSTF found insufficient evidence to recommend for or against routine screening with ECG, ETT, or EBCT scanning for coronary calcium for either the presence of severe CAS or the prediction of CHD events in adults at increased risk for CHD events. Grade: I Statement

Other Recommendations:

The U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening adults for glaucoma. I recommendation.
The USPSTF recommends against screening adults for chronic obstructive pulmonary disease (COPD) using spirometry. D Recommendation

These recommendations are for screening in asymptomatic persons. They are not recommendations against testing for a disease in the presence or symptoms or other factors where making a diagnosis may alter management decisions.
At first glance these recommendations may seem disappointing. Intuitively it seems like early diagnosis of cancer, glaucoma, coronary disease or chronic lung disease should lead to better outcomes. Unfortuntely the data does not lead to those conclusions. In some cases like prostate cancer screening the early diagnosis may lead to more morbidity and problems from testing and treatment than benefits of the earlier diagnosis provide. In other situations like screening for coronary disease screening the high incidence of false positive tests and the low prevalence of disease make screening impractical. In still other situations like COPD making the diagnosis does not lead to effective interventions that alter the course of the disease.
I am grateful that the USPSTF puts out these recommendations, and am hopeful that they will become more active again after political pressure of late seems to have slowed the pace of their production to a point where new recommendations are needed in important areas like PSA screening.

2 Comments - Leave a comment!

The Unexpected Health Benefits of Running

September 12, 2011 Dr. Pullen

The Unexpected Health Benefits of Running

by Charles Boren

The ancient Greeks used running as a form of training and competition. It was a way to test personal fortitude and improve physical health. Many of the health benefits of running were known even in those ancient times. In modern times, many start running for the same reasons. They run to improve their physical endurance, lose weight and build muscle. While these common health benefits of running influence many to start running, runners are surprised to learn just how extensive the health benefits are. Running improves the quality of sleep, fights off depression and anxiety, and improves joint health and stability.

Sleep disorders affect a surprising percent of the population today. There is good news to those who suffer from them. Running can actually improve the decrease the symptoms of sleep disorders and improve the quality of sleep. It also appears to help people sleep more efficiently. That is, the amount of time spent actually sleeping while in bed increases. Running helps people fall asleep more quickly, toss-and-turn less through the night, and wake up more rested than those who do not run.

The runner’s high is a well-documented phenomenon, and major benefit, of running. This is a unique feeling often reported during long, strenuous amounts of exercise. The feeling can range from relaxed and peaceful to intensely euphoric. It is produced when endorphins flood the brain as part of a stress response to running. These endorphins are the natural drugs of the body. They reduce pain and are responsible for the happy and content feelings similar to many those produced by narcotics. While many runners experience this phenomenon, many do not realize the long-term positive effect that is has. Over time, the regular doses of endorphins to the brain can combat both anxiety and depression. In fact, many studies have shown that following a regular running program markedly reduces the symptoms of these disorders.

A common misconception is that the high-impact nature of running negatively affects the joints in the body. The truth is that running may actually improve joint health and stability. (1) This is done in a number of ways. First, running helps keep excess weight off. Just a ten-pound increase in body weight can cause a 45-pound increase in stress on the knees (2). Second, running causes cartilage to expand and contract with the natural movements created while running. This forces nutrients and oxygen into the cartilage cells. Without this, the cells will slowly die from oxygen depletion and starvation. Third, running strengthens the tendons and ligaments that support and stabilize joints. This prevents injury in the long-term. Overall, running greatly improves joints and prevents the onset of arthritis.

Building muscle, losing weight, and strengthening the heart are the health benefits that motivate people to start running. However, it is the unspoken benefits that keep them running. As a whole, runners have better sleep, improved mental states, and healthier joints. Many runners feel that they are taking responsibility for their health by running. They physically feel better, less stressed and they have peace of mind. This is a reward all in itself.

Bio: Charles spends much of his free time running. On the side he also runs an automotive company, where he purchases vehicles.

5 Comments - Leave a comment!

Tabex for Smoking Cessation

September 10, 2011 Dr. Pullen

Tabex for Smoking Cessation: One More Tool for Smokers Trying to Quit

Tabex was reported in the prestigious New England Journal of Medicine to be more effective than placebo for help in quitting smoking. Sounds great until you read the actual numbers. Tabex was shown in a single fairly small study including only 740 patients that was conducted in Poland to have a 1 year success rate of 8.4% as compared to a 2.4% success rate with placebo. Admittedly this sounds like it is helpful in a small percentage of patients, but at best only about 1 in 12 patients using Tabex will be successful in quitting smoking.

Still having an inexpensive and over the counter product patients can use to try to get help in quitting smoking is exciting. Studies show that most smokers would like to quit smoking. Smoking rates have decreased significantly in the United States over the last couple of decades, but many patients in my practice just cannot seem to quit smoking. Chantix has been quite helpful for many patients, but significant Chantix side effects including cardiovascular concerns, vivid dreams, depression and even suicidality have been deterents to Chantix use. The high price of Chantix is also a major deterrent to widespread use. Bupropion, originally marketed as Zyban for smoking cessation, is sometimes helpful, but far from a panacea.

Tabex, chemical name cytosine, is structurally similar to nicotine, and functions as a nicotinic acetylcholine receptor agonist. It is an extract of the seeds of Golden Rain acacia (Cytisus laborinum) and Chantix is actually a derivative of cytosine and has been approved for smoking cessation in the U.S. since 2006. Tabex has b een used in Europe for nearly 40 years for smoking cessation and has been produced by a Bulgarian company Sopharma AD.

In the NEJM study Tabex was used on a 25 day tapering schedule, taking 6 tablets daily for the first 3 days, five tablets on days 4-12, and then tapering more quickly by taking 4 days on 4/day, 4 days on 3/day, until stopping on day 25 after 2 days of two tablets daily. At this dose toxicity seemed minimal, although the authors admit the study was too small to find uncommon adverse effects of Tabex. Cytisine has been documented to have serious side effects at much higher doses, so users should not take more than this regimen used in the NEJM study.

Tabex appears to be inexpensive, on E-bay I found vendors selling #100 1.5 mg tablets for $13.35 USD. This would amount to enough pills for a person to take the recommended 25 day regimen and have just a few pills left over. This compares to Chantix which costs about $179/ month at Drugstore.com.

This small NEJM study implies that this inexpensive, seemingly fairly safe drug, available without a prescription, is marginally effective for helping smokers quit the habit. I think it may be worth a try for smokers who have been unable to quit using nicotine replacement systems, cannot tolerate, cannot afford or have reasons not to use Chantix, and are motivated to quit. The long term adverse health effects of continuing to smoke seem to far outweigh the risks of essentially all of the smoking cessation aides for patients without specific contraindications to their use.

In European use for over 40 years there does not seem to have been much in the way of serious problems with Tabex use, and I anticipate the use of Tabex to increase significantly in the U.S since the NEJM article has given more validity to its use.

There is really little to no evidence that the other SSRI drugs like citalopram or sertraline help patients to quit smoking.

The abstract of the NEJM article is available here.

What do you think? - Leave a comment!

Brilinta: Is It Really Better than Plavix?

September 5, 2011 Dr. Pullen

Headline: Brilinta Reduces Death Rates vs. Plavix in Acute Coronary Syndrome!

Tagline: But Not By Much, and at a High Cost.

July 20, 2011 AstraZenica received FDA approval for their new antiplatelet agent Brilinta (ticagrelor) for use in acute coronary syndrome. Brilinta joins an increasingly crowded market of antiplatelet agents that includes the longstanding leader in the class Plavix and Effient, which came to market July 10, 2009. Effient has not become terribly popular, likely due to its higher rate of bleeding complications including life threatening bleeding and an increased incidence of stroke in patients with previous stroke. These risks seem to have held sway over the modestly reduce rate of restenosis of coronary artery stents seen in Effient vs. Plavix patients when used post coronar artery stent placement.

The primary selling point of Brilinta is that in the PLATO clinical trial the mortality rate in patients with acute coronary syndrome was stastically significantly lower in patient using Brilinta (9.8%) vs. Plavix (11.7%) P<0.001. Patients on Brilinta had lower death rates from heart attack and stroke, but had higher rates of non-fatal bleeding complications. The reversible mechanism of action of Brilinta has its drawbacks though, requiring twice daily dosing vs. daily dosing with Plavix.

The primary issue with Brilinta is whether this statistically significant reduction in death rates in acute coronary syndrome is practically significant, and whether the potential drawbacks of twice daily dosing and the non-compliance issues this may engender will erode those benefits when used for longer periods of time. When the Plavix patent expires soon and generic clopidogrel becomes available the benefits of Brilinta and its current high cost of $7.24/day will need to be enough to make that cost difference palatable. Plavix has been an effective, well tolerated and extremely popular drug. It is the third highest gross sales drug in the US (2009 data) and is anticipated to be available as an inexpensive generic in about May 2012.

These are some of the pros and cons that patients and physicians will need to consider when making a decision between Plavix and Brilinta

Plavix	Brilinta
Pros:	Pros:
Long track record and well understood	Slightly lower death rate in acute coronary syndrome
Currently less expensive than Brilinta, soon to be much less expensive after generic Plavix is available May 2012.	No hepatic metabolism needed
Once Daily Dosing	Can be used with proton pump inhibitors
Cons:	Cons:
Slightly less effective in acute coronary syndrome	Higher cost, soon to be much higher
Loses efficacy used with Proton Pump Inhibitors	Twice daily dosing may reduce compliance
	New drug, after market side effects to be determined
	Efficacy reduced with aspirin doses >100 mg daily

Brilinta, like Plavix and Effient works as a platelet aggregation inhibitor, but acts with a slightly different mechanism of action, binding at a site different from the ADP receptor it blocks. It is a reversible receptor inhibitor, and Brilinta, unlike Plavix does not require hepatic activation which may be a potential advantage in some patients. The importance of the hepatic metabolism issue in overall efficacy is unclear, and this may be just a theoretic issue of little clinical significance.

Brilinta currently has a black box warning similar to that with Plavix warning against use in patients with active bleeding, a history of intracranial hemorrhage, and tha bleeding should be suspected in any patient with hypotension who has had a recent procedure like CABG, coronary angiography or any other surgery. Unlike Plavix the black box warning also includes an increased risk of cardiovascular events if Brilinta is discontinued, making the twice daily dosing and compliance an even larger concern. The black box warning also noted the reduced effectiveness of Brilinta if aspirin at doses higher than 100 mg daily are used. This could easily be done inadvertently in patients taking OTC aspirin products. If you do not personally have a history with Aspirin usage, consider this resource about aspirin side effects.

An unexpected issue with Brilinta is a much higher incidence of dyspnea (13%) vs Plavix (7%).

In summary I expect Brilinta to be a niche product used in uncommon circumstances once clopidogrel becomes available as an inexpensive generic.

What do you think? - Leave a comment!

Apixaban – The Likely Frontrunner in the New Anticoagulant Market?

August 29, 2011 Dr. Pullen

Apixaban, brand name Eliquis, is expected to gain FDA approval by the end of 2011 and is likely to become the most widely used of these drugs because of what appears to be not just non-inferiority to warfarin but superiority in major outcomes. Apixaban will join Pradaxa and Xarelto among the novel new anticoagulant drugs that can be used as an alternative to warfarin for patients who need potent drugs to prevent blood clotting in disorders like atrial fibrillation and deep vein thrombosis of the legs. Apixaban, to be marketed by Bristol-Meyers Squibb and Pfizer as Eliquis seems to be possibly the most exciting of these drugs so far. In a study of over 18000 patients with atrial fibrillation called the ARISTOTLE Study apixaban was the first of the drugs to show statistically significant superiority to warfarin in the key endpoints of incidence of bleeding complications (31% lower), risk of stroke (21% lower) and risk of death (11% lower). Showing superiority vs. warfarin is going to be a key to successful marketing of these drugs because the generic warfarin is widely available and strongly entrenched in the marketplace. All of these new drugs are going to be expensive, and in order to achieve widespread use they will need to prove superiority in both safety and efficacy.

All of the drugs released so far work as direct inhibitors at one point or another in the coagulation cascade, unlike warfarin which as a vitamin K antagonist works by reducing the production of key clotting factors. Apixaban and Xarelto are factor Xa (X as the Roman numeral for 10, and “a” for activated) inhibitors, and Pradaxa is a direct thrombin inhibitor. They are immediately active in their functional roles after being absorbed from the gut, and so the speed of action of these drugs is much faster than the speed of action of warfarin. This is likely to play a key role in looking at the overall cost of use of these drugs. Warfarin use requires several days to take effect, and the necessary dose is highly variable. From significant personal experience I can say that when quick anticoagulation is needed as in DVT management there are two major drawbacks to warfarin use. First it is necessary to treat patients with heparin initially in order to get prompt anticoagulation. Secondly it is very common to take a week or more to achieve therapeutic levels of anticoagulation. Often the initial dose chosen is either too high or too low. The prothrombin time, or more commonly the INR, is used to measure the degree of anticoagulation with warfarin. Dosing of warfarin can be anywhere from <1 mg daily to 15 mg daily, and is difficult to predict. It is not uncommon to have patients significantly over anti-coagulated a week after starting warfarin requiring that the dose be reduced, only to then to reduce the dose and a few days later find that they are now significantly under anti-coagulated. This yo-yo effect necessitates frequent INR monitoring and visits to have INR testing. Essentially all of the new drugs work within one to two days, and are twice a day dosed because of relatively short half-lives. Although twice daily dosing may seem a drawback due to patient compliance issues (vs. once daily warfarin dosing), I see it a potential benefit because its corollary is that the drug will be out of the system quickly so that any bleeding complications will likely be short lived when they do occur.

Warfarin can be reversed with vitamin K or fresh frozen plasma, but the use of vitamin K takes at least a couple of days, and use of fresh frozen plasma exposes patients to human blood product risks. I see the faster onset and faster loss of efficacy of apixaban and Pradaxa as significant benefits.

This combined with superiority in three major measures of efficacy and safety for apixaban make it likely that when this drug is approved for use in the U.S. that it will become a very popular new drug. Pradaxa is already gaining traction among cardiologists in stroke prevention in atrial fibrillation patients, but I suspect that unless Pradaxa can show superiority rather than its current “non-inferiority” claims to warfarin that apixaban may quickly gain favor among physicians and patients. Another drug rivaroxiban is already on the market in Europe and has shown non-inferiority to warfarin in stroke prevention, superiority in bleeding risk, but did not improve overall survival in comparison to warfarin.

apixaban vs warfarin	Pradaxa vs. warfarin	rivaroxiban vs warfarin
Lower risk of Strokes in a-fib	Possibly Lower risk of Strokes in a-fib	Non-inferiority re Stroke prevention in a-fib
Lower risk of Bleeding	Mixed data on risk of Bleeding	Lower Risk of Bleeding
Lower mortality	No mortality data	No reduction in mortality

Apixaban is in phase three clinical trials and is expected to receive FDA approval by the end of 2011. Some market analysts anticipate that apixaban may end up the overall winner in the competition for the leading position among the new anticoagulant drugs. I suspect that they are correct because to this point only apixaban can claim significant superior efficacy and safety in comparison to warfarin. I expect warfarin use to be significantly impacted because in addition to the increased efficacy and increased safety, its use eliminates the need for INR monitoring. The real question is going to be whether the first-to-market advantage of Pradaxa is enough to hold off apixaban, and whether insurance companies perceive there is an overall cost benefit to paying for the new drugs.

Another issue is that Pradaxa is only approved for use in non-valvular atrial fibrillation for stroke prevention, and Xarelto is only approved at this time for post-operative DVT prevention in total joint replacement patients. It is likely that apixaban will only get an indication for stroke prevention in non-valvular atrial fibrillation. I expect wider indication approvals to be forthcoming for this class of drugs as there is little reason to expect that they will not also work for therapy of DVT and DVT prophylaxis in hypercoagulable states. Stay tuned to see if apixaban gains the popularity that some predict it is destined to have.

What do you think? - Leave a comment!

Benefits of Resistance Exercise

August 29, 2011 Dr. Pullen

In recent years it has become clear that in order to reap the full benefits of exercise that both aerobic exercise and resistance exercise is important. The recommendation of the CDC for adults of all ages is to incorporate strength exercises into the exercise regimen at least 2 days a week. Technically resistance exercise and strength exercise are not synonymous, but for practical purposes the terms are interchangeable. Resistance exercise is exercise where the major muscle groups exert force against a resistance. When the goal of this type of exercise is to increase strength it is strength exercise.

So what are the benefits of resistance exercise? Actually they are multiple, some obvious and others less obvious.

Resistance Exercise Builds Strength: This is one of the obvious benefits, but some aspects may not be appreciated. One aspect that some may not fully appreciate is that this benefit does not go away with age. One study of the elderly (average age 87) showed that an 8 week program of resistance training 3x/ week increased strength by over 100%, increased walking speed by 12%, and reduced the incidence of falls. With the sedentary life style many jobs enforce, and the lack of outdoors physical work by many of us, resistance training can make a huge difference in the way we feel, in our functional capacity to do tasks without hurting ourselves, and in our overall functional capacity.
Resistance Training Builds Bone Strength: Bones are a living tissue, constantly remodeling based on the stress loads placed upon them. Resistance training while bearing weight can lead to increased bone strength and help prevent the fractures of osteoporosis as we age.
Resistance Training Helps Lower Mild Hypertension: Aerobic exercise is the backbone of maintaining cardiovascular health, but resistance training also helps reduce blood pressure to at least some degree.
Resistance Training can Increase Metabolic Rate: Aerobic exercise is again the mainstay of weight control and maintenance, but there is considerable evidence that resistance training when combined with aerobic training leads to higher metabolic rate and more weight loss than aerobic training alone.
Improved Self Image: This is just my opinion and experience, but I believe that maintaining strength, physical capability and muscle mass is has a positive effect on self-image. I know I feel better about myself when I feel strong and fit. Resistance exercises are a key to this for me.

If you believe in the benefits of resistance exercise how should you go about setting up a program? First be real with yourself. Set goals that you believe are possible, sustainable and affordable. You can go to a gym, buy free weights or machines for home, or simply do exercises using your own body weight like pushups, pull-ups, and squats. Rubber band type resistance equipment is inexpensive and very effective. Secondly aim for 3 days a week for resistance exercise. Taking a day between training sessions gives the muscles exercised time to recover and grow. Third learn from Milo of Croton in that progressive overload is the principle behind steadily increasing strength. You don’t need a calf to carry every day until it has grown. Just start with exercises where 8-15 repetitions lead to fatigue. Once this is easy, slightly increase the resistance. Keep increasing the resistance as the exercise becomes easy. Last if a certain exercise leads to persistent pain, change something rather that thinking you can work through the pain. Often some minor change may avoid an overuse injury.

Add resistance training to your regular exercise to reap the full benefits of exercise. Enjoy.

2 Comments - Leave a comment!