Most Read Articles
01 Oct 2013

Heart disease is still New Zealand’s biggest killer, with one Kiwi dying from coronary heart disease every 90 minutes. Pharmacy Today New Zealand looks at how pharmacists can help

Pearl Toh, 11 Oct 2017
Clinical practice is an art guided by good science, and clinical practice guideline (CPG) is meant to guide in integrating the art and science of clinical practice for the long-term benefits of patients, said Dr Abdul Rashid Abdul Rahman, a consultant cardiovascular physician at An-Nur Specialist Hospital in Bangi, Malaysia, during the 13th Asian-Pacific Congress of Hypertension (APCH) held in Singapore.
Dr. James Salisi, 01 Jul 2014

The recent spike in the number of new cases of human immunodeficiency virus (HIV) infection in the Philippines means that clinicians and pharmacists alike may need to increase their awareness and competency in prescribing and monitoring HIV treatment. Although taught in medical and pharmacy schools, the scarcity in exposure to clinical cases before highlights the need to for physicians and pharmacist to review HIV pharmacotherapy in order to cater to the increasing HIV patient population.

01 Sep 2017
Complementary medicines can play an important part in maintaining wellness, preventing deficiencies and optimizing health outcomes, says Dr Lesley Braun PhD, Director of the Blackmores Institute. 

Evacetrapib provides no benefit on cardiovascular outcomes in high-risk patients

08 Jul 2017

Treatment with the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib does not appear to effectively reduce the rate of cardiovascular events in patients with high-risk vascular disease compared with placebo, although the drug has positive effects on established lipid biomarkers, a study has shown.

The multicentre, randomized phase III trial randomized 12,092 patients to receive either evacetrapib 130 mg or matching placebo, administered daily in addition to standard medical therapy. All patients presented with at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease.

First occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina was assessed as the primary efficacy endpoint.

After a median of 26 months of treatment, the primary endpoint occurred in 12.9 percent of patients who received evacetrapib vs 12.8 percent of those who took placebo (hazard ratio, 1.01; 95 percent CI, 0.91 to 1.11; p=0.91). The lack of efficacy led to the early termination of the trial.

Despite the lack of efficacy, a 31.1-percent decrease in the mean low-density lipoprotein (LDL) cholesterol level was seen with evacetrapib vs a 6-percent increase with placebo at 3 months of treatment. Additionally, the mean high-density lipoprotein (HDL) cholesterol level increased by 133.2 percent with evacetrapib vs only by 1.6 percent with placebo.

CETP modulates the transfer of esterified cholesterol from HDL to apolipoprotein B–containing lipoproteins. Previous studies have found that CETP inhibition might potentially induce off-target toxic effects, such as increased blood pressure and increased plasma levels of aldosterone, resulting in higher rates of death and cardiovascular events. [Arterioscler Thromb Vasc Biol 2003;23:160-7; N Engl J Med 2007;357:2109-22]

Evacetrapib is a CETP inhibitor with no evidence the said off-target effects. It substantially raises the HDL cholesterol level, reduces the LDL cholesterol level and enhances cellular cholesterol efflux capacity. The lack of efficacy against cardiovascular events vs placebo in the present trial may be explained by several factors. One is that the beneficial vascular effects of HDL particles, such as cholesterol efflux capacity, may be attenuated in patients who have coronary artery disease or acute coronary syndromes. [Circ Res 2014;114:171-82; Nat Rev Cardiol 2016;13:48-60]

“Alternatively, some clinicians have expressed concern that the inhibition of CETP pathways may produce HDL particles that are dysfunctional, although the protective effects of genetic loss-of-function polymorphisms of CETP do not support this hypothesis,” researchers noted. [Nat Rev Drug Discov 2008;7:143-55]

“The profile of change in HDL lipid particles and the enhancement of cellular cholesterol efflux with evacetrapib suggest that the HDL cholesterol produced by this agent should be functional, but this concept of functionality has yet to be validated as a predictor of therapeutic benefit,” they added. [N Engl J Med 2014;371:2383-93; Lancet Diabetes Endocrinol 2015;3:507-13]

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Most Read Articles
01 Oct 2013

Heart disease is still New Zealand’s biggest killer, with one Kiwi dying from coronary heart disease every 90 minutes. Pharmacy Today New Zealand looks at how pharmacists can help

Pearl Toh, 11 Oct 2017
Clinical practice is an art guided by good science, and clinical practice guideline (CPG) is meant to guide in integrating the art and science of clinical practice for the long-term benefits of patients, said Dr Abdul Rashid Abdul Rahman, a consultant cardiovascular physician at An-Nur Specialist Hospital in Bangi, Malaysia, during the 13th Asian-Pacific Congress of Hypertension (APCH) held in Singapore.
Dr. James Salisi, 01 Jul 2014

The recent spike in the number of new cases of human immunodeficiency virus (HIV) infection in the Philippines means that clinicians and pharmacists alike may need to increase their awareness and competency in prescribing and monitoring HIV treatment. Although taught in medical and pharmacy schools, the scarcity in exposure to clinical cases before highlights the need to for physicians and pharmacist to review HIV pharmacotherapy in order to cater to the increasing HIV patient population.

01 Sep 2017
Complementary medicines can play an important part in maintaining wellness, preventing deficiencies and optimizing health outcomes, says Dr Lesley Braun PhD, Director of the Blackmores Institute.