Key Words:
cholesterol, statins, guidelines
In 2013, the American College of Cardiology and the American
Heart Association jointly has brought out a new set of
guidelines on treatment of high blood cholesterol [1]. These
guidelines suggest practices that meet the patients' need, but
are not a substitute for proper clinical assessment and
decision making. The ultimate decision regarding the treatment
of the patient rests with the healthcare provider and the
patient. All the guidelines are based on the results of
multiple randomized clinical trials that are well designed and
well executed and done in the past few years which have shown
substantial benefit to patients. These data have been used to
identify the patients who are most likely to benefit from
cholesterol lowering statin therapy. The present guidelines
address the treatment of adults ≥ 21 years of age. It is
presumed that these recommendations will benefit both primary
care physicians and specialists who are involved in the
prevention of Atherosclerotic Cardiovascular Disease (ASCVD).
The Expert Panel did not recommend the continued use of
specific LDL-C and/or non-HDL targets for treatment as it did
not find evidence to favor treatment to target. Further, it
also states that nonstatin therapies do not provide acceptable
ASCVD risk reduction compared to their potential for adverse
effects when used in the routine use of ASCVD. This guideline
recommends the use of statins based on an estimated 10-year
ASCVD risk in both white and black men and women [2]. Though
there is no recommendation for Asians or Indians, the African
American can be chosen while calculating the risk for Indians
and Asians as per this guideline. The guideline also used the
trials to identify the relevant safety considerations in
individuals receiving treatment of high blood cholesterol.
This guideline focusses on the ASCVD Risk reduction and has
identified four distinct groups of patients who would benefit
from reductions in blood cholesterol. These groups are as
follows.
1. Individuals with clinical ASCVD.
2. Individuals with primary elevation of LDL-C ≥ 190 mg/ dL
3. Individuals 40 - 75 years of age with diabetes and LDL-C
70 - 189 mg/ dL.
4. Individuals without clinical ASCVD or Diabetes mellitus
who are 40 - 75 years of age with LDL-C 70 - 189 mg/dL and
an estimated 10-year ASCVD risk of 7.5 % or higher.
These groups have a potential for ASCVD risk reduction benefit
clearly exceeding the potential for adverse effects in adults.
Clinical ASCVD is the presence of Acute coronary syndromes, a
history of myocardial infarction, Stable or Unstable angina,
coronary or other arterial revascularizations, stroke,
transient ischemic attacks or atherosclerotic peripheral
arterial disease. The 10 year ASCVD risk is calculated as per
the guidelines on Assessment of Cardiovascular risk of the
ACC/AHA. [2]. However, it has to be emphasized that lifestyle
modifications like adhering to a heart healthy diet, regular
exercise, avoidance of tobacco products and maintenance of a
healthy weight is the most important factors in ASCVD
risk reductions in addition to drugs in the control of blood
cholesterol [3].
Based on the trials, the Expert Panel defined the intensity of
statin therapy on the basis of the average expected LDL-C
reduction than the absolute values of LDL-C or goals.
Consequently, the Panel has recommended the use of "High
Intensity", "Moderate Intensity" and "Lower intensity" statin
therapy for various groups of patients. The details are as
follows.
1. High Intensity Statin Therapy. Here,
the daily dose of statin lowers LDL-C
by approximately ≥ 50%. This
is achieved with atorvastatin 40 - 80 mg or Rosuvastatin 20
- 40 mg.
2. Moderate Intensity Statin Therapy. Here, the daily dose
lowers LDL-C by approximately 30 - 50%. This is achieved by
Atorvastatin 10 - 20 mg, Rosuvastatin 5 - 10 mg, Simvastatin
20 - 40 mg, Pravastatin 40 -80 mg, Lovastatin 40 mg or
Pitavastatin 2 - 4 mg.
3. Low Intensity Statin Therapy. Here, the LDL-C lowering is
approximately ≤ 30%. It may be achieved with Simvastatin 10
mg, Pravastatin 10 - 20 mg, Lovastatin 20 mg or Pitavastatin
1 mg.
In the recommendations regarding the initiation or
continuation of statin therapy, two groups of individuals were
not included. They are (1) Individuals with NYHA class
II-IV heart failure and (2) Individuals undergoing maintenance
hemodialysis. This recommendation is in contrast to the ATP
III guidelines. This was because of the lack of sufficient
information from clinical trials to base recommendations for
or against statin treatments. It is also recommended that
individuals receiving statins should be counseled on healthy
lifestyle habits and also be evaluated for new-onset diabetes
according to the current diabetes screening guidelines [4].
Statins are also contraindicated in pregnancy and should not
be used in women of childbearing potential unless these women
are using effective contraception and are not nursing.
The present guideline is different from the ATP III guideline
of 2002 in many aspects. [5]. Whereas the ATP III guideline
advised the use of multiple medications to reduce LDL-C below
a target level, the present guideline recommends the use of
statin alone in patients between the age of 40 and 75 years
with a 7.5% or higher 10-year risk of ASCVD. Whereas in
the previous ATP III guideline, a baseline LDL-C level of ≥
130 mg/dL and a 10-year cardiovascular risk of 10 - 20% were
candidates for drug therapy, in the present guideline a
baseline LDL-C level of 190 mg/dL would require addition of
drug therapy (statin). The ATP III guideline suggested the use
of statins in patients on hemodialysis whereas the present
guideline discourages the routine use of statin in patients
undergoing hemodialysis. Liberal use of add-on agents were
recommended in ATP III guidelines for lowering LDL-C level
whereas the present guideline relegates the use of drugs other
than statins to the non-preferred therapy.
Deficiencies in the present guideline
There have been criticisms about the present guidelines and a
few deficiencies have been pointed out by critics. It is worth
noting these too in the context of the present guidelines. A
few of the deficiencies noted are as follows:
1. The present guidelines do not offer guidelines
on the management of increased Triglycerides or the
management of low HDL-C levels along with an increase of
blood cholesterol levels.
2. The use of high intensity statins in the age group >
75 years has not been addressed due to the lack of adequate
controlled clinical trials.
3. It has been criticized that the Cardiovascular Risk
estimate based on the 2013 publication over estimates the
cardiovascular risk in individuals and hence may lead to
unnecessary statin therapy in some groups of individuals.
4. The subject of Primary prevention of ASCVD in individuals
> 75 years has also not been addressed in this
recommendation.
5. Alternate treatment strategies for ASCVD risk reduction
in those not tolerant to statins have not been adequately
recommended in this guideline.
Only time will tell whether these guidelines will be of
benefit to the population at large who are at risk of
developing ASCVD and whether the criticisms regarding these
guidelines will be adequately addressed in days to come.
References
1. 2013 ACC/ AHA guideline on the treatment of blood
Cholesterol to reduce atherosclerotic cardiovascular risk in
Adults. J. Am. Coll. Cardiol. 2013. 1 - 84.
2. David CG, Donald ML, Glen B, Sean C, Ralph BD Sr.,
Raymond G, Philip G, Daniel TL, Daniel L, Christopher JO,
Jennifer R, Sanford S, Susan TS, Sidney CS Jr., Paul S, Neil
JS and Peter WFW. 2013 ACC/AHA Guideline on the Assessment of
Cardiovascular Risk. A report of the American College of
Cardiology / American Heart Association Task force on Practice
Guidelines. Circulation 2013. Nov 12, 2013. (Published
online)
3. Eckel RH, Jakicic JM, Ard JD et al. 2013 AHA/ ACC
guideline on lifestyle management to reduce cardiovascular
risk. A report of the ACC/ AHA task force on
Practiceguideline. Circulation 2013. Nov 12 (Published
online).
4. American Diabetes A. Standards of medical care in diabetes
2013. Diabetes Care 2013: 36 Suppl. 1. S11-66.
5. National Cholesterol Education Panel. Third report of the
National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation and Treatment of High Blood Cholesterol
in Adults (Adult Treatment Panel III) final report.
Circulation 2002. 106: 3143-3421.