This document summarizes a study that investigated whether simvastatin could prevent exacerbations in patients with moderate to severe COPD. The study involved 885 patients randomized to receive either simvastatin 40mg daily or a placebo. The primary outcome was the exacerbation rate, and secondary outcomes included time to first exacerbation, lung function, quality of life, and adverse events. The results showed no significant differences between the simvastatin and placebo groups in exacerbation rate, time to first exacerbation, or secondary outcomes. Simvastatin 40mg daily did not demonstrate a therapeutic benefit for reducing exacerbations in patients with moderate to severe COPD.

1. Pokhara University
School of Health and Allied Sciences
Simvastatin for the Prevention
of Exacerbations in Moderate-
to-Severe COPD
Anita Yadav
First Semester, MPharm(Clinical Pharmacy)
School of Health and Allied Sciences
Pokhara University, Dhungepatan, Pokhara Lekhnath-30, Kaski,
Nepal

2. Pokhara University
School of Health and Allied Sciences
Topics under discussion
• Introduction
• Methods
• Results
• Discussion
• Conclusion
• References
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3. Pokhara University
School of Health and Allied Sciences
Introduction
• Chronic Obstructive Pulmonary Disease (COPD) is the
third leading cause of death in the United States.
• It is characterized by acute exacerbations that are
associated with increased hospitalizations and costs
of care, worsened quality of life, and increased
mortality.
• Effective therapies for the treatment or prevention of
exacerbations are limited.
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4. Pokhara University
School of Health and Allied Sciences
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• Statins are 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase inhibitors that reduce the risks
of acute cardiac events and death.
• Although widely used for their lipidlowering effects,
statins are also reported to have anti-inflammatory
effects.
• Multiple retrospective studies have shown that
statins are beneficial in COPD.

5. Pokhara University
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• The Prospective Randomized Placebo-Controlled
Trial of Simvastatin in the Prevention of COPD
Exacerbations (STATCOPE) was a prospective,
multicenter trial conducted by the National Heart,
Lung, and Blood Institute (NHLBI) COPD Clinical
Research Network.
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6. Pokhara University
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Materials and Methods
Study Design and oversight
• In this randomized, parallel-group, placebo-
controlled trial, participants were randomly assigned
in a 1:1 ratio to receive simvastatin orally at a dose
of 40 mg or an identical-appearing placebo once
daily.
• Participants were recruited from 45 sites (29 sites in
the United States and 16 in Canada).
• Written informed consent was obtained from all
participants. The institutional review board at each
center approved the study protocol.
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7. Pokhara University
School of Health and Allied Sciences
• The study drugs, simvastatin and placebo, were
purchased, prepared, and supplied by Temple University
School of Pharmacy.
Participant Population
• Have moderate or severe COPD
• supplemental oxygen
• Be 40 to 80 years of age Inclusion Criteria
• Be a current or ex-smoker
• Not have active heart disease
or high cholesterol
• Not be taking statins Exclusion Criteria
• Not have diabetesAugust 8, 2017
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8. Pokhara University
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Outcomes
• The primary outcome was the effect of simvastatin
on the exacerbation rate, which was defined as the
number of exacerbations per person-year.
• Secondary outcomes included the time to the first
exacerbation, the severity of exacerbations, the
number of acute cardiovascular events, quality of
life, and changes in spirometric variables.
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9. Pokhara University
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Study visits
• Participants were followed at clinic visits every
months and by means of monthly telephone
contacts.
• Spirometric variable and quality of life assessed with
the use of the St. George’s Respiratory Questionnaire
[SGRQ] and the Medical Outcomes Study 36-Item
Short-Form Health Survey [SF-36] were measured at
baseline and at 12,24, and 36 months.
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10. Pokhara University
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INTERIM ANALYSIS, STOPPING GUIDELINES, AND
MONITORING PLAN
• The data and safety monitoring board met
approximately every 6 months to review recruitment
and follow-up rates, study-drug adherence, safety,
and efficacy results.
• The rates of moderate and severe exacerbations did
not differ significantly and the numbers of deaths
were similar (27 deaths in the simvastatin group and
26 in the placebo group). The data and safety
monitoring board therefore voted to stop STATCOPE.
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11. Pokhara University
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STATISTICAL ANALYSIS
• Performed with the use of Kaplan–Meier methods,
• Curves were compared with the use of the log-rank
test.
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12. Pokhara University
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RESULTS
ENROLLMENT AND FOLLOW-UP
• Enrollment began March 4, 2010 to October 11,
2013.
• Screening for the study, randomization, and follow
up of the participants are shown in Figure 1.

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14. Pokhara University
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Fig 1. Screening, Randomization, and Study Completion.

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School of Health and Allied Sciences
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CHARACTERISTICS OF THE PARTICIPANTS
• We randomly assigned 885 participants with COPD to
the two study groups. A total of 44% of the patients
were women.
• 430 patients in the simvastatin group and 447 in the
placebo group were included in the primary analysis

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Fig. Characteristics of Patients

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COPD EXACERBATIONS
• A total of 1982 acute COPD exacerbations occurred
during the study: 965 exacerbations among the 430
patients in the simvastatin group and 1017
exacerbations among the 447 patients in the placebo
group.
• The COPD exacerbation rates were similar in the
simvastatin and placebo groups: (P = 0.54) (Fig. 2).
• The median number of days to the first exacerbation
was also similar in the two groups: 223 days in the
simvastatin group and 231 days in the placebo group (P
= 0.34) (Fig. 3)

19. Pokhara University
School of Health and Allied Sciences
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Figure 2. Acute Exacerbations of Chronic Obstructive Pulmonary Disease
per Person-Year, According to Study Group.

20. Pokhara University
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Figure 3. Effect of Simvastatin on the Time to the First Acute Exacerbation
of Chronic Obstructive Pulmonary Disease. There were no significant between-group
differences in the time to the first exacerbation. The median time to the first
exacerbation was 223 days (95% CI, 195 to 275) in the simvastatin group and 231 days
(95% CI, 193 to 303) in the placebo group.

21. Pokhara University
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SECONDARY OUTCOMES
• There was no effect of simvastatin on lung function
as assessed spirometrically. Likewise, simvastatin
had no effect on the general or respiratory specific
quality of life, as assessed by the SF-36 and SGRQ,
respectively.
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22. Pokhara University
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ADVERSE EVENTS
• The most common adverse events, aside from
exacerbations, were pneumonia and other respiratory
and cardiovascular events.
• Except for nonfatal serious adverse events involving
the gastrointestinal tract, which were more frequent
with simvastatin than with placebo (in 30 patients
[0.05 events per personyear] vs. 17 patients [0.02
events per person-year], P = 0.02) (Table 2)
• There were 28 deaths in the simvastatin group and 30
in the placebo group (P = 0.89).
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Fig. Nonfatal Serious Adverse Events and Fatal Events, According to
Study Group.

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PERMANENT DISCONTINUATION OF STUDY DRUG AND
STUDY WITHDRAWAL
• The most common reason for discontinuation of the
study drug was the use of incompatible medications;
other common reasons were a diagnosis of diabetes and
the FDA warning about additional incompatible
medications.
• A small number of participants had myalgias or
abnormal laboratory values, but the rates did not differ
according to study-drug assignment.
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26. Pokhara University
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Discussion
• In this large, prospective, multicenter, randomized trial,
we found that 40 mg of daily simvastatin had no effect
on the frequency of exacerbations.
• The rates of serious adverse events were low and similar
in the two study groups. These data show that daily use
of 40 mg of simvastatin has no role in preventing
exacerbations in moderate-to-severe COPD.
• The results differ from previously reported findings that
statins prevent exacerbations, attenuate lung-function
decline, and reduce mortality among patients with
COPD.
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27. Pokhara University
School of Health and Allied Sciences
Conclusion
• In conclusion, simvastatin at a dose of 40 mg daily, in
addition to usual care, did not reduce the exacerbation rate
or prolong the time to the first exacerbation among
patients with moderateto- severe COPD who were at high
risk for exacerbations.
• Furthermore, simvastatin had no effect on lung function,
quality of life, the rate of severe adverse events, or
mortality.
• Thus, these data did not show a therapeutic benefit of
statins in patients with moderate-to-severe COPD.
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28. Pokhara University
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References
• Criner GJ, Connett JE, Aaron SD, Albert RK, Bailey
WC, Casaburi R, Cooper JAD, Curtis JL, Dransfield MT,
Han MK, Make B, Marchetti N, Martinez FJ,
Niewoehner DE, Scanlon PD, Sciurba FC, Scharf SM,
Sin DD, Voelker H, Washko GR, Woodruff PG, and
Lazarus SC(2014) Simvastatin for the Prevention of
Exacerbations in Moderate-to-Severe COPD, N Engl J
Med, 370(23), 2201-2210.
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29. Pokhara University
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Thank You
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