Reversing Heart Disease: Combination of PCSK9 Inhibitors and Statins – Opinion by Steven Nissen, MD, Chairman of Cardiovascular Medicine at Cleveland Clinic
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 1/31/2024
Lipoprotein(a) Is Markedly More Atherogenic Than LDL: An Apolipoprotein B-Based Genetic Analysis
Original Research
J Am Coll Cardiol. 2024 Jan, 83 (3) 385–395Editorial Comment: Particle Number and Characteristics of Lipoprotein(a), LDL, and apoB: Perspectives on Contributions to ASCVD∗Lipoprotein(a) (Lp(a)) is recognized as a causal factor for coronary heart disease (CHD) but its atherogenicity relative to that of low-density lipoprotein (LDL) on a per-particle basis is indeterminate.
Conclusions
We conclude that the atherogenicity of Lp(a) (CHD risk quotient per unit increase in particle number) is substantially greater than that of LDL. Therefore, Lp(a) represents a key target for drug-based intervention in a significant proportion of the at-risk population.
SOURCE
https://www.jacc.org/doi/10.1016/j.jacc.2023.10.039
The term “atherogenicity” is used since 1986 [5] referring to the accumulation of intracellular lipids, which is a trigger of cellular atherogenesis
Atherogenic dyslipidemia (AD) refers to elevated levels of triglycerides (TG) and small-dense low-density lipoprotein and low levels of high-density lipoprotein cholesterol (HDL-C). In addition, elevated levels of large TG rich very low-density lipoproteins, apolipoprotein B and oxidised low-density lipoprotein (LDL), and reduced levels of small high-density lipoproteins plays a critical role in AD. All three elements of AD per se have been recognised as independent risk factor for cardiovascular disease. LDL-C/HDL-C ratio has shown excellent risk prediction of coronary heart disease than either of the two risk markers. Asian Indians have a higher prevalence of AD than western population due to higher physical inactivity, low exercise and diet deficient in polyunsaturated fatty acids (PUFA).
SOURCE
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872713/
While nearly 10% of middle-age adults in China have high risk for cardiovascular disease, only 0.6% of these high-risk individuals use statins and 2.4% take aspirin, a national screening project reported in the Annals of Internal Medicine.
UPDATED on 5/5/2017
Europeans Mull PCSK9i Post-FOURIER Fallout on Clinical Practice
Patrice Wendling, May 04, 2017
But it was panelist Dr Stephen Nicholls (University of Adelaide, Australia) who took aim at the elephant in the packed auditorium. At an annual cost of about $14,100 for evolocumab and $14,600 for alirocumab (Praluent, Sanofi/Regeneron), the important question facing cardiologists is who will be eligible for these drugs “in a world where we can’t just write a scrip for every FOURIER-type patient; we won’t be allowed to.”
He suggested initially this will include patients with familial hypercholesterolemia and only those with established atherosclerotic CVD whose LDL-C remains unacceptably high despite therapy. Future FOURIER subanalyses may define other eligible high-risk groups.
UPDATED on 3/14/2017
PCSK9 Inhibitor Access Snarled in Red Tape, Rejections
Patrice Wendling, March 21, 2017
To determine whether this experience is happening nationwide, Navar and colleagues examined first PCSK9 prescriptions in 45,029 patients (median age 66 years; 51% female) between August 1, 2015 and July 31, 2016 in the Symphony Health Solutions database, which covers 90% of retail, 70% of specialty, and 60% of mail-order pharmacies in the US.
Nearly half (48%) of prescribers were cardiologists, and 37% were general practitioners. Most patients (52%) had government insurance, typically Medicare, and 40% had commercial insurance.
In the first 24 hours after being submitted to the pharmacy, 79.2% of prescriptions were rejected. Ultimately, 52.8% of all PCSK9 prescriptions were rejected.
Of special note, 34.7% of prescriptions for the pricy lipid-lowering drugs were abandoned at the pharmacy.
How 2 Drugs Lower Cholesterol Remarkably — and Reverse Heart Disease
Study shows promise for combination of newer drug and statins
Newer cholesterol-lowering drugs combined with more conventional medicine reduces bad cholesterol to incredibly low levels, a new study shows. Perhaps even more important, the combination also reduces the heart-attack-inducing plaque that forms inside the arteries, the study says.
The study was led by cardiologist Steven Nissen, MD, Chairman of Cardiovascular Medicine at Cleveland Clinic. Results appeared recently in the Journal of the American Medical Association (JAMA).
The study looked at the use of a drug called evolocumab by people who took statins to lower the amount of LDL, or bad, cholesterol in their blood. Evolocumab is a drug called a PCSK9 inhibitor. This is a newer kind of medicine that can make LDL cholesterol levels plummet.
The people who took statins and evolocumab had greater reductions in atherosclerosis compared with people who took statins and a placebo. Atherosclerosis is a disease in which plaque builds up inside your arteries. The condition can lead to serious problems, including heart attack, stroke, or even death.
The results are an intriguing indicator — rather than definite proof — that evolocumab may have benefit for patients taking statins, Dr. Nissen says. Researchers are still awaiting the results of large clinical trials investigating whether evolocumab is safe and will prevent heart attack, stroke or death. The first results of these studies are expected in April 2017.
Special ultrasound
In the study, researchers treated for 18 months 968 high-risk people who had extremely high levels of blood cholesterol.
Participants were randomly assigned to take either a statin and a placebo, or a statin and evolocumab.
Researchers monitored the participants’ cholesterol levels. They also used a special ultrasound probe to measure the amount of plaque in their arteries at the beginning and the end of the study.
“We were able to show that getting the bad cholesterol levels down to really low levels, down to the 20s and 30s, can actually remove plaque from the coronary arteries,” Dr. Nissen says. “This going to levels that we’ve never been able to achieve before.”
Low cholesterol, less plaque
Results show the group treated with statins and a placebo reduced their LDL cholesterol levels to 93 on average. At the same time, the group treated with the combination of the statin plus evolocumab got down to an average bad cholesterol level of 36.6.
“No one’s ever reached levels that low in a clinical trial,” Dr. Nissen says.
Participants who took evolocumab also had less plaque in their arteries at the end of the study — essentially reversing their heart disease.
“We, for the first time now, have shown that this new class of drugs, the PCSK9 inhibitors, has a favorable effect on the development of plaques on the coronary artery and can actually regress those plaques,” Dr. Nissen says. “And it turns out about two-thirds of patients actually had less plaque at the end of 18 months than they started with.”
PCSK9 inhibitors, which are expensive, are not for everybody, Dr. Nissen says. Currently, the drug is used in addition to statins for the highest-risk patients with particularly high cholesterol.
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