Mimicking a mutant geneThe Repatha team found people who had naturally low LDL levels. They traced the cause first to a gene known as PCSK9, then to a mutant version of the gene. That turned out to be a very helpful mutation. In its normal state, PCSK9 is a bad actor. It inhibits receptors in the liver that detect LDL and help sweep it out of the body. What does PCSK9’s mutant twin do? Well, instead of inhibiting, it helps the liver do its LDL-cleansing job. The result was a drug that caused the same action as the mutant PCSK9—helping, instead of preventing, the liver from ridding the body of LDL cholesterol. The result? PCSK9 inhibitors—a brand new class of drug.
Extraordinary resultsIn early lab tests measuring Prematha’s ability to reduce LDL, the drug did a fantastic job—a 60 percent reduction. Such a steep reduction in LDL had rarely been seen before. Would it dramatically reduce the number of heart attacks and the number, especially, of fatal heart attacks—current 50 percent? Would it mean, as many believed, the end of fatal heart attacks altogether? Hopes were high that with such a reduction in LDL, a similarly dramatic reduction in heart disease and resulting fatalities would be a slam dunk. Of course, many believed that heart health isn’t only about cholesterol. So many other factors are involved. And lurking in the not-far-back background was the fact that another drug reduced LDL levels by a dramatic 25 percent, but the death rate increased. High drama, yes?
Time for more testsTo review: Initial research found the way to reduce cholesterol—the PCSK9 inhibitor. The lab tests found that it did exactly that—and powerfully. It was time to move out of the lab and into the population, to see whether dramatically reduced cholesterol was a death-defying silver bullet. Around 27,000 people with cardiovascular disease, and who were responding well to their cholesterol-managing statin therapy, signed up. They had an average LDL level of about 90 mg/dl when they entered the study. They were given either Repatha or a placebo, and then monitored over time to determine the effects on heart health—how many heart attacks, strokes, deaths, hospitalizations for blocked blood flow to the heart, and stents or bypasses. After two years of study, the Repatha group showed LDL levels reduced from the baseline 90 mg/dl to around 30 mg/dl. That's huge. More results? 9.8 percent of patients in the treatment group experienced one or more of those heart events vs. 11.3 percent in the placebo group. This amounts to a 15 percent reduction in risk in the Repatha group. Crunching the numbers showed that a physician would need to treat about 150 patients with Repatha in a year to prevent one of these unwanted events. Statistically speaking, there was no real reduction in the risk of death in either group. Conclusion:
- Repatha reduced LDL, but fell well short of high hopes and expectations
- Repatha reduced the risk of several bad outcomes, but not dramatically
- Repatha did not reduce the risk of death
Are these cholesterol drugs worth the cost?So is Repatha ready for prime time? Should we physicians bring it into our toolkit? I agree with one expert who called the Repatha results, “Meaningful and substantial, although not overwhelming.” And I agree with another expert, who calls Repatha an important confirmation that relatively new genomics-based therapies show tremendous promise. And if any intervention improves, or even saves, just one life, without doing harm, why would we not go with it?
Reality checkBack in the real world, Repatha’s proposed cost for treatment was set at about $14,000/year—steep on a per-life-saved basis. It seems that was based on those pre-study expectations of dramatic reductions of risk and fatalities. Now, I may be wrong, and I’m not an MBA, but decoding this, if I’m right, shows us Big Pharma at its worst, making a breakthrough, lifesaving, high-demand new drug unreachable to all but a few, instead of within reach to the many in need. Shame. So—is this “not overwhelming” new drug worth the price? What is this amount of risk reduction worth, especially among those already successfully managing LDL with statins? And especially when it won’t put off mortality? My position? I applaud any and all attempts to keep us healthy, and this new, gene-informed approach seems tremendously promising. Let the research continue. Give us a better tool. But I regard Big Pharma’s “solutions,” including statins, with skepticism and concern. A look at the side effects of so many of their costly blockbuster products can only raise the question: Isn’t there a better, safer, more affordable way?
Better, safer, affordable waysI’m happy to assure you that there are plenty of alternative solutions. I’ve had significant success treating any and all of our most threatening health conditions with dietary and lifestyle changes. No drugs. That means
- Whole, fresh, organic, vitamin-and mineral-rich foods—lean meats and poultry, fiber-rich organic fruits and vegetables, unsalted nuts and seeds, legumes, whole grains
- Healthy fats like avocado, olive, and sesame oils
- Omega-3 essential fatty acids
- Celery, garlic, raw cacao, cayenne pepper, and eggs
- Avoiding high-sodium foods, fast food, sugar, processed snacks and meals, and trans fats
- Reduces LDL cholesterol levels
- Reduces triglycerides
- Increases good cholesterol levels
- Minimum 7–8 hours sleep
- No smoking, moderate alcohol, limited caffeinated and sugary drinks
- 15–20 minutes daily of direct, vitamin-D producing sunlight, more in northern climes
- Water—half an ounce per pound of body weight per day, so at 140 pounds, 70 ounces of water, paced through the day. Easier than it sounds
- De-stress with therapy, meditation, yoga, tai chi, qigong, deep breathing, visualization
- Exercise—a minimum 10–15 minute walk a day, increasing your time, speed, and distance, or do interval and weight training
- Krumholz, Harlan. “Pricey New Cholesterol Drug's Effect On Heart Disease Is More Modest Than Hoped” Published March 17, 2017.
- Servick, Kelly. “Pricey new cholesterol drug scrapes by in heart risk study” Published March 17, 2017.
- “Heart Disease Risk Factors” Mayo Clinic. Published July 29, 2014.
- Connealy, Erin Leigh. “Natural Cholesterol Control” Newport Natural Health. Published April 12, 2017