Medical community in India in specific and in the world in general has believed in the idea that the cholesterol puzzle is completely solved. The belief was reflected in the way most of the doctors reassure the patients regarding the cholesterol levels, promising them that a bit of life-style modification and one or two safe drugs usually do the trick. But of late, two major setbacks happened in the treatment of high cholesterol, which the general public has every right to know:
The first setback: One of the biggest victories in medical science was attributed to the cholesterol lowering agents: statins. This group comprises of various medications like Simvastatin, Pravastatin, Atorvastatin, and Rosuvastatin. A Japanese scientist Dr. Akira Endo discovered a fungal metabolite that could block cholesterol synthesis in 1976. Year after year, new trials were unleashed with various statins, various designs and yet with a common message: that statins are safe, lifesaving and cost effective.
Like the cynics claim, all the good things come to an end sooner or later. However, with statins, it was only the first major roadblock, which stunned the medical profession. The FDA (the food and drug administration) of the USA has issued a boxed warning late last year that the statins may increase the risk of Diabetes Mellitus. From then a new phrase has cropped up in the medical literature: Statin-Induced Diabetes.
Statins increase the risk of new onset diabetes by 12%. The higher the dose of the statin, the higher is the risk of Diabetes. However, even in these patients who got diabetes while on statin treatment, had lesser cardiovascular events with statin. So it is still unclear whether Statins actually do any harm. Among all the patients treated with statins, every one in 200 patients seem to get new onset diabetes. But statins do prevent a heart attack in every two of a 100 patients treated. So, those for whom statins are really indicated should not be afraid to use them, but those with border-line indications should discuss with their cardiologist whether they need the same dose of the statin that they are taking, or less would suffice.
So, for the take home message: Statins are still the wonder drugs and prevent heart attacks in people at high risk of having them. Of late, it is found that these drugs could increase the risk of Diabetes. The benefits of statins clearly outweigh the risks involved. However, statins cannot be prescribed to everybody, especially in high doses. There are clear guidelines for starting the statin treatment and they have to be strictly followed.
The sorry story of low HDL Treatment: The second setback: HDL cholesterol is the good cholesterol. It was found that people who have high HDL cholesterol live longer than those with low HDL cholesterol. Investigations have found medications to increase the HDL cholesterol. These medications included Niacin, CETP inhibitors, and IV HDL infusions. All these medications were proved to improve the blood HDL cholesterol. But the problem was that none of these drugs helped in reducing the cardiovascular risk. So, none of the present medications raising HDL, would help the patients in reducing their risk of heart disease, despite increasing the HDL impressively.
The most touted of these agents was Niacin. Niacin increases HDL levels handsomely and though had a few side-effects, scientists found solutions to mitigate these side-effects by adding another agent to Niacin, namely Laropiprant. However, in the late 2011, a large trial named AIM- HIGH was published which not only failed to show any benefit by Niacin, but also showed slightly increased risk of stroke in patients who used Niacin. The last nail in the coffin for Niacin came late last year when a big Merck-sponsored trial (THRIVE-CV) was stopped before completion, because of lack of efficiency.
CETP inhibitors improve the HDL levels aggressively. However, the first of these agents, Torcetrapib, was withdrawn because of an increase in liver related side-effects. A newer CETP inhibitor, Enacetrapib is still undergoing rigors of clinical trials, but as of this moment its future does not look too bright.
The take home messages: First, low HDL which increases heart attacks, is very common in Indians. Second, treatments to improve HDL levels are effective in raising the HDL levels. Third, these treatments do not decrease the heart attack risk and lastly, research is still needed to identify agents which decrease the heart attack risk and raise HDL levels rather than finding agents which just increase the HDL.
The more we understand about the cholesterol and its adverse effects on the heart, the more we realize the complexity of modifying it for the better. Though a lot of progress was made in the treatment of abnormal cholesterol, still a lot needs to be done. The general public meanwhile should closely watch the developments because everyone is going to be affected by these.
- Dr. M.S.S. MUKHARJEE
MD, DM (CARDIOLOGY), DNB (CARDIOLOGY)
Founder-Director; Pulse Heart Center, KPHB, Panjagutta.
Mobile Number : 9848014716