The results of the Heart Protection Study were announced in November at the American Heart Association conference. This study was conducted in Britain and involved randomizing 20,500 volunteers, at high-risk for heart disease, to either 40 mg Zocor (a statin – one type of cholesterol lowering medication) or a placebo. They were then followed for 3-5 years and the incidence of heart attacks, strokes and re-vascularizations (procedures to open or by-pass blocked blood vessels) was assessed. There was also an additional part in the study where they randomized volunteers to a nutritional supplement containing 250 mg vitamin C, 600 IU vitamin E and 20 mg of beta carotene compared to those taking a placebo. The announcement of the results was a front page story in both the Vancouver Sun and the National Post last November. You can also find information on the study at www.hps.com.
What were they thinking?
The Zocor Arm. As a reminder Zocor is a member of the statin family of cholesterol lowering medications. It acts in the liver by inhibiting an enzyme involved in the synthesis of LDL, the ‘bad’ cholesterol. All of the statins on the market definitely work and typical LDL cholesterol reductions are in the order of 35 to 60% depending on the type and dose of statin used. LDL is believed to function as the ‘bad’ cholesterol in that it can contribute to the deposition of fat on arterials walls leading to narrowing and even blocking blood vessels. It follows therefore, that if we are able to lower the LDL cholesterol in a high-risk group of volunteers, then we should see a reduction in events such as heart attacks, strokes and revascularization procedures.
The Vitamin Arm
It is generally believed that antioxidants in the blood can reduce the activity of unstable free radicals which are thought to contribute to the progression of disease states such as heart disease and cancer. Therefore, by boosting the levels of the bloods antioxidants we would also hypothesize a reduction of events as mentioned above. With this in mind individuals were randomized to either placebo or a daily vitamin regimen of 250 mg vitamin C, 20 mg beta carotene, and 600 IU vitamin E.
The Findings In The Vitamin Arm
There was no significant effect of the vitamin intervention. While the investigators were disappointed with this result it really isn’t that surprising. They didn’t approach the vitamin arm from the same aggressive perspective that they did the statin arm. I spoke with a dietician who reviewed the doses of vitamins used and she made it clear that they did not approach the accepted safe upper limit. This was especially true for vitamin C as 250 mg daily is barely a supplemental level for most people, not a therapeutic dose. Doses of vitamin C in the 1000-2000 mg range are tolerated by most people, especially if taken as a slow release form. Given the doses for all three vitamins they used I don’t feel the protocol design allowed the vitamin supplement question to be properly addressed.
There are cardiologists and researchers in this field who feel differently. Vancouver’s Dr. Jiri Frohlich feels this study is ‘the nail in the coffin for antioxidants for people with heart disease’ and he is not alone. Many experts in this field of research feel this has once and for all answered the antioxidant question in terms of prevention of heart disease. Some of the experts do agree, however, that antioxidants started at an earlier age or in nutritionally deficient populations could theoretically provide some benefit although this has yet to be demonstrated.
The Zocor Arm Findings
The results of the Zocor arm of the study really were quite convincing. What was found was that all events including heart attacks, strokes and revascularization procedures were significantly reduced in those individuals taking Zocor compared to those individuals taking the placebo. This was found to be true regardless of age, sex, heart disease history or prior cholesterol levels. They found that risk was reduced even for people who had normal cholesterol at the start of the study.
The overwhelmingly positive results of this study are likely going to influence the prescribing habits of many physicians. This will not be a surprise given the scientific merit of this study and the strength of the conclusions. Unfortunately they may lose sight of what the study demonstrated. It showed that lower LDL and total cholesterol in a high-risk group reduced events and saved lives. We should use this information as incentive and as a catalyst for addressing the causes of elevated cholesterol and take a stronger preventative approach rather than accepting statin therapy as the first step.
Implications To Our Health Care System
Let’s consider the cost implications of putting people in BC on Zocor at 80 dollars a month. The newspaper quoted Dr. Rory Collins, the study’s lead investigator, as saying the results showed that treating 14 people for 5 years would prevent 1 heart attack/stroke/revascularization. The cost of Zocor for 14 people would be $67,200 and then we must consider the additional cost of GP visits and monitoring liver/muscle enzymes for safety purposes since not everyone tolerates statins. That’s the cost for 14 people to prevent one event. The study authors add that for every 40 individuals treated for 5 years we could save one life. The cost of saving one life therefore, would be approximately $192,000. In terms of BC let’s consider putting 100,000 Lower Mainland people (5% of 2 million) on Zocor since it estimated that about 5% of Canadian adults are on some statin and these numbers are likely to increase following the release of these study findings. That works out to almost 480 million dollars over five years to prevent an estimated 7140 events and 2500 deaths. Canada wide this could represent over 7 billion dollars. These are rough estimates but it is clear that it could represent a significant amount of our health budget and we must ask two questions. Is it worth it? Could these events and deaths have been prevented by other means?
It is true that when the patent on Zocor expires a cheaper generic form of Zocor should reduce the overall cost to the health care system. I contacted the local pharmacy to compare the cost of some of the generic statins currently available with the brand name original. The two generics available were 21% and 37% cheaper than their brand name versions and the cheapest was approximately half the cost of Zocor, the statin used in the Heart Protection Study. Be aware efficacy does vary between different statins and dosing.
Will these expenses be offset by savings in hospitalizations and reduced burden on health care by the high risk individuals who would benefit the most from statin therapy? The care for patients with vascular disease is extremely expensive in terms of emergency visits, surgeries, rehabilitation etc and there is no doubt the savings would be substantial. Whether they would offset the costs is not known. I would suggest that a large scale cost-benefit assessment be performed before we put millions more Canadians on statins.
The New Aspirin?
Dr. Collins even went so far as to say that #39;statins are the new aspirin#39; based on their findings and the potential therapeutic applications. There are at least two major differences between aspirin and statins. Aspirin is only pennies a day and the cost is typically absorbed by the patient. Secondly, there is the safety issue and the cost associated with it. I don#39;t know any physicians who recommend blood safety tests for aspirin users. It isn’t required whereas typically a GP would arrange a blood test to check on a patient’s liver enzymes following initiation of statin treatment to make sure the patient is tolerating the medication. Referring to statins as the ‘new aspirin’ is misleading from a cost and safety perspective even though it may be true from the perspective of reduced events and deaths.
Not All Statins Are Created Equal
The study showed that Zocor does not appear to present a major safety risk based on the data in this study, the details of which were not provided. Dr. Salim Yusuf, Division of Cardiology at McMaster University, suggests that the safety profile for Zocor in this study was actually better than that for ASA. This is of course the best safety data we have yet on statins. For that reason many doctors will likely prescribe Zocor for patients just starting on a statin since safety has been demonstrated. It is not reasonable to assume that all other statins will have the same safety performance over the long term since they are all a little different. This is clear from the recent experience with cerivastatin (Baycol) which was removed from the market following a number of deaths and adverse experiences as a result of rhabdomyolysis, a potentially life-threatening condition which occurs when a large number of skeletal muscles die. Baycol may be unique in terms of some of it’s properties yet all statins present a potential danger. As the use of different statins becomes wide-spread it will be important to monitor patients who start taking them.
Our Unhealthy Heart Crisis
What was most sobering in the media articles that followed the HPS announcement was that there are so many high-risk people. Maybe some of the 7 billion dollars that may get spent on statins in Canada over the next 5 years could be spent on programs that try to address the underlying causes of the current Unhealthy Heart Crisis. The statin may do its prevention ‘thing’ regardless of lifestyle changes which is sad in a way. The statin doesn’t necessarily improve the health of any individual. What it does is reduce the risk of heart attack and stroke by 25%. We should think of good health as a sense of wellness and a high quality of life, not merely as a low-risk factor. High risk is often a function of being overweight, inactive, smoking and having a poor diet. We may have someone on a statin who is just as unhealthy as before or perhaps worse. They are simply at lower risk of heart attack and stroke and therefore represent less potential burden on the cardiovascular component of the health care system.
Could a degree of risk reduction have been accomplished by other means? I think the answer to that is yes. Lifestyle modification is one of the simplest ways to reduce your risk for the progression of heart disease and the eventual reduction of MIs and Stroke. The foundation is diet, exercise and stopping smoking. These changes lead to a major improvement in the quality of life, more energy and they empower the individual at the spiritual level giving them a sense of control over their life. One lifestyle convert is often enough to infect 10 others by example and through enthusiastic conversation. That can be a wonderful thing to witness and share in the ongoing cycle of healthy changed lives. Furthermore, if individuals do experience an MI or stroke the better fit individuals tend to have more rapid recoveries, shorter hospital stays and better long-term prognosis.
Could a lifestyle intervention arm have accomplished what this study accomplished with Zocor? With 100% compliance perhaps, but in the real world I don’t believe so as much as I would like to. The incredible amount of lowering of LDL cholesterol with statins is virtually impossible to achieve consistently with lifestyle intervention. In a group of 20,000 research volunteers compliance with pill taking is far more likely than compliance with a time consuming, energy demanding change in diet and activity. At the individual level however we can all make our own choices about changing our lives and LDL isn’t the only risk factor. Don’t let my earlier statement discourage you from making positive changes in your lifestyle because those changes will make a difference to your entire body, not just your heart disease risk profile.
Statins will undoubtedly play a key role in treating patients who are at high-risk for heart disease. There are people who will benefit from and who should be on statins. Given the recent findings of the Heart Protection Study there may be a trend to put a far greater number of lower-risk people on statins. If you are one of the low-risk individuals considering statins I would ask that you consider all your alternatives, and ask your doctor plenty of questions.
Eric Norman is a research scientist investigating heart disease.