Coronary Artery Disease
Conditions
Brief summary
The goal of this study is to determine if one dose of simvastatin will decrease the inflammatory response to coronary intervention. Also to determine if one dose of simvastatin affects endothelial function (activity of the artery) as measured by noninvasive peripheral artery tonography.
Detailed description
The objective of this study is to determine if acute pretreatment with simvastatin, an HMG-CoA reductase inhibitor will reduce the post inflammatory response after percutaneous coronary interventions (PCI), and/or change endothelial function as assessed by peripheral arterial tomography (PAT). Percutaneous coronary intervention (PCI), commonly known as coronary angioplasty or simply angioplasty, is a non-surgical procedure used to treat the stenotic (narrowed) coronary arteries of the heart found in coronary heart disease. Patients will be pretreated with simvastatin 80 mg prior to undergoing PCI. Endothelial function will be assessed before and after treatment via PAT. Our working hypothesis is patients pretreated with simvastatin, will have 1) attenuated inflammatory response, as noted by decreased levels of serum high sensitivity CRP and IL-6 and 2) improved endothelial function as compared to patients not pretreated with statin therapy.
Interventions
DRUGSimvastatin
Subjects randomized to this arm will be pretreated with 80 mg (2 pills) simvastatin approximately one hour prior to percutaneous coronary intervention.
DRUGPlacebo
Subjects randomized to this arm will be pretreated with 2 placebo pills approximately one hour prior to percutaneous coronary intervention.
Sponsors
Merck Sharp & Dohme LLC
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients undergoing PCI/angiography * No previously known side effects of statins * Patients who sign an informed consent * Age \> 18 years old
Exclusion criteria
* Patients with ST elevation myocardial infarction * Patients with cardiogenic shock * Patients with hypersensitivity to statins * Patients with unexplained muscle pain * Patients with acute liver disease * Patients receiving cyclosporine, antifungal azoles, macrolide antibiotics, niacin, fibrates\> 1 quart grapefruit juice/day or nefazodone * Patients with creatinine \> 2.0 * Patients with known malignancy * Ejection Fraction \< 25% * No coronary care unit patients * No outpatients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum High Sensitivity C-Reactive Protein (hsCRP) | baseline, within 24 hours post percutaneous coronary intervention | The hsCRP test evaluates vascular inflammation. People with higher hsCRP values have the highest risk of cardiovascular disease, and those with lower values have less of a risk. The American Heart Association and U.S. Centers for Disease Control and Prevention have defined risk groups as follows: Low risk: less than 1.0 mg/L Average risk: 1.0 to 3.0 mg/L High risk: above 3.0 mg/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Endothelial Peripheral Arterial Tomography (EndoPAT) Score After PCI | baseline, within 24 hours post percutaneous coronary intervention | The EndoPAT is a noninvasive test that involves putting probes on the index fingers of both hands and evaluating the blood flow to one hand before and after inflating a blood pressure cuff on one arm, temporarily reducing blood flow to the fingers. The finger sensor on the affected arm will now show no blood flow, while the sensor on the opposite index finger will continue to display your normal blood flow level. After several minutes, the blood pressure cuff is released, allowing blood to flow back into the affected lower arm. If the finger sensor on the affected arm shows a rush of blood, the blood vessels are functioning normally. If the blood flow return is sluggish, however, the blood vessels are unhealthy. The results are reported as the Endoscore (range 0-3); a score of 1.67 and lower indicates the need for immediate medical attention; a score between 1.68 and 2 indicates a need to reduce risk factors; a score above 2.1 indicates a healthy heart. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled at the Mayo Clinic in Rochester, MN from 2002 until 2008.
Pre-assignment details
66 subjects signed informed consent, but 9 subjects had to have the PCI procedure too quickly, and could not participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| Simvastatin Subjects randomized to this arm will be pretreated with 80 mg (2 pills) simvastatin approximately one hour prior to percutaneous coronary intervention. | 28 |
| Placebo Subjects randomized to this arm will be pretreated with 2 placebo pills approximately one hour prior to percutaneous coronary intervention. | 29 |
| Total | 57 |
Baseline characteristics
| Characteristic | Simvastatin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 15 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 14 Participants | 31 Participants |
| Region of Enrollment United States | 28 participants | 29 participants | 57 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 20 Participants | 21 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 28 | 0 / 29 |
| serious Total, serious adverse events | 0 / 28 | 0 / 29 |
Outcome results
Primary
Change in Serum High Sensitivity C-Reactive Protein (hsCRP)
The hsCRP test evaluates vascular inflammation. People with higher hsCRP values have the highest risk of cardiovascular disease, and those with lower values have less of a risk. The American Heart Association and U.S. Centers for Disease Control and Prevention have defined risk groups as follows: Low risk: less than 1.0 mg/L Average risk: 1.0 to 3.0 mg/L High risk: above 3.0 mg/L
Time frame: baseline, within 24 hours post percutaneous coronary intervention
Population: The study was terminated early because not enough subjects could be recruited.
Secondary
Change in Endothelial Peripheral Arterial Tomography (EndoPAT) Score After PCI
The EndoPAT is a noninvasive test that involves putting probes on the index fingers of both hands and evaluating the blood flow to one hand before and after inflating a blood pressure cuff on one arm, temporarily reducing blood flow to the fingers. The finger sensor on the affected arm will now show no blood flow, while the sensor on the opposite index finger will continue to display your normal blood flow level. After several minutes, the blood pressure cuff is released, allowing blood to flow back into the affected lower arm. If the finger sensor on the affected arm shows a rush of blood, the blood vessels are functioning normally. If the blood flow return is sluggish, however, the blood vessels are unhealthy. The results are reported as the Endoscore (range 0-3); a score of 1.67 and lower indicates the need for immediate medical attention; a score between 1.68 and 2 indicates a need to reduce risk factors; a score above 2.1 indicates a healthy heart.
Time frame: baseline, within 24 hours post percutaneous coronary intervention
Population: The study was terminated early because not enough subjects could be recruited.