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Tugas Cme: Secondary Prevention of CVD
Tugas Cme: Secondary Prevention of CVD
Pembimbing:
Disusun Oleh :
PURWOKERTO
2019
LEMBAR PENGESAHAN
TUGAS CME
Disusun oleh:
Pembimbing,
Doctor: I've looked at your results for today, and I'm quite concerned.
Patient: Alright...
Patient: OK.
Doctor: The statin has brought your low-density lipoprotein cholesterol, or LDL-C,
down to 3.1 mmol/L, or 120 mg/dL, but I would like to see it lower still. Your high-
density lipoprotein cholesterol, or HDL-C, is only 0.9 mmol/L, or 35 mg/dL -- and
that's the good cholesterol -- so we want it to be a little higher.
Patient: I see.
Doctor: Sarah, you have already had one heart attack, and all of these things are
putting you at great risk of having another one, or of having a stroke.
Doctor: Well, one of the things that would help with your blood glucose, your blood
pressure, and your cholesterol is losing some weight. We have talked about this
before.
Doctor: I'm going to ask the nurse to sit down with you again to try to identify
specific things you can do in terms of your diet to lower your weight. I will also
give you a prescription to take part in an exercise program.
Doctor: I think that we need to be more aggressive about controlling your blood
glucose, so I would like to add a medication called sitagliptin.
Patient: Does that do the same thing as the other diabetes medications?
Doctor: Yes. I would also like to protect your heart more by further lowering your
blood pressure. So I’m going to prescribe 5 mg a day of amlodipine, which should
help with that.
Doctor: Yes, I know. But you're at very high risk of having another heart attack. If
you can get your weight down, as I said, that will help, and we may be able to cut
back on the medications. But I think we should go with this for now, and then see
where you are in 6 weeks' time.
Patient: Alright, doctor.
Since Sarah is at high risk for another CV event, CV risk factor management
is critical to her care. Which of the following CV risk factor goals/targets of therapy
is most appropriate for Sarah?
Patient: Yes, I've made some adjustments to what I cook -- although I don't think
my husband is always crazy about it. And I go to the exercise sessions twice a week.
I actually feel better afterward, and I seem to have more energy some days.
Doctor: Your BP is also quite a bit lower now -- down to 130 over 80 mm Hg,
which I'm comfortable with.
Doctor: There has been some improvement in your HbA1c since we added the
sitagliptin, but not a lot -- that has dropped to 7.8%. How have you been doing with
that?
Patient: It's been alright, on the whole. I've have had a couple of hypos -- I was
getting dizzy, and when I checked my blood sugar it was down around 4 mmol/L.
Doctor: Hmm, yes, that can happen sometimes -- when people are taking a
medication such as sitagliptin and their glucose starts to fall, it is easier to get hypos
if they are also taking a sulfonylurea like the glipizide that you're on.
Patient: I see.
A. I would not make a change at this time, but would have the patient return in
3 months to recheck her HbA1c
B. Increase glipizide to 10 mg four times daily
C. Switch glipizide 5 mg four times daily to extended-release glipizide 20 mg
once daily
D. Discontinue glipizide and sitagliptin and add a glucagon-like peptide-1
receptor agonist (GLP-1 RA) or sodium-glucose cotransporter 2 (SGLT2)
inhibitor
As we see, the changes to therapy introduced after the initial visit have resulted
in some improvements. For example, the addition of amlodipine to the angiotensin
receptor blocker, valsartan, and hydrochlorothiazide has resulted in good BP
improvement. Her HbA1c is also down, but remains elevated; the choice of a DPP-
4 inhibitor was perhaps not optimal. DPP-4 inhibitors are often selected as add-on
therapy to metformin and other glucose-lowering agents because they are well-
tolerated, orally administered, and convenient to use. However, as we see with this
patient, their HbA1c reduction is fairly modest (<1%); and their effects on weight
and CV risk are, in general, neutral.[8] In this patient, a better choice for additional
HbA1c reduction might have been a glucagon-like peptide-1 receptor agonist
(GLP-1 RA) or a sodium-glucose cotransporter 2 (SGLT2) inhibitor, as both types
of agents provide greater HbA1c reduction compared with DPP-4 inhibitors.
Moreover, GLP-1 RAs and SGLT2 inhibitors are associated with weight loss. Since
the patient has a history of clinical CVD, adding an agent that provides CV
protection against new ischemic events should be considered.[8]
Four large, CV outcome trials (CVOTs) have been conducted with GLP-1 RAs
in patients with T2DM and high CV risk or established CVD.[10-13] All of the
trials demonstrated CV safety of the active GLP-1 RA therapy. In addition, the
LEADER and SUSTAIN-6 trials found that treatment with either liraglutide (in the
LEADER trial) or semaglutide (in the SUSTAIN-6 trial) significantly reduced the
risk for the primary major adverse CV event (MACE) endpoint, a composite
endpoint of the first occurrence of death from CV causes, nonfatal MI, or nonfatal
stroke, compared with placebo, when added to conventional treatment.[11,12]
Two large CVOTs have been conducted with SGLT2 inhibitors in patients
with T2DM and high CV risk: the EMPA-REG OUTCOME trial and the CANVAS
trial[14,15] demonstrated CV safety of their respective SGLT2 inhibitor.
Furthermore, treatment was associated with a significant reduction the risk for the
primary MACE endpoint compared with placebo.[14,15]
Based on the results of these and other CVOTs, a number of countries and
organizations are changing recommendations regarding the use of glucose-lowering
therapy in patients with clinical CVD. For example, the 2018 Clinical Practice
Guidelines from Diabetes Canada suggest using an antihyperglycemic agent with
demonstrated CV benefit, including liraglutide, empagliflozin, or canagliflozin.[16]
The 2018 American Diabetes Association, or ADA, Standards of Diabetes Care
recommend incorporating an agent proven to reduce MACE and CV mortality
(currently empagliflozin and liraglutide), after considering drug-specific and patient
factors.[8,17]
For this patient, selection of a GLP-1 RA or an SGLT2 inhibitor might have
made it possible to discontinue the sulfonylurea (SU), due to the significant
glucose-lowering effect of these agents. Discontinuation of the SU is desirable since
the patient has complained of some hypoglycemic episodes. SUs stimulate the
release of insulin and are associated with a high risk for hypoglycemic episodes.
These hypos are more common in elderly people and may be associated with
arrhythmia, including serious ventricular ones.[18]
Doctor: I would really like to continue to try to get your blood glucose much lower
-- that will reduce the chances of you having the severe problems that can occur
with diabetes, such as nerve pain and poor vision. It will also lower your risk of
having another heart attack or a stroke.
Doctor: So here is what I would recommend: I think you should stop taking both
the glipizide and the sitagliptin that you started 6 weeks ago. Instead, I would like
you to try a newer medication, liraglutide.
Patient: Will I have to take this new medicine 4 times a day, like the glipizide?
Doctor: No, actually, this is an injection that you give yourself. It lasts for 24 hours,
so you only have to take it once a day.
Patient: An injection?
Doctor: Yes, it comes in a pen-like device. It's very easy, not like using a syringe.
Most people get used to it very quickly.
Patient: Alright.
Doctor: This medication should be good for you, Sarah. It does several things at
once, including stimulating the secretion of your body's own natural insulin, as well
as slowing down the absorption of glucose by the intestine and reducing appetite as
an indirect effect of a delay in gastric emptying. So it lowers both fasting glucose
and the glucose spikes that occur after meals.
Doctor: Yes. And together with the changes in your diet and the exercise program
that you're doing, liraglutide may also help you lose weight.
Doctor: Your tests show an LDL-C level of 3.0 mmol/L, or 116 mg/dL, which is
more or less the same as it was at your last visit. So I'm going to give you a
prescription for ezetimibe -- it's a medication that works with your statin to lower
LDL-C further.
Patient: Alright.
Doctor: I'm going to arrange for the nurse to speak to you about the liraglutide
injection, and then I'd like to see you again in about 2 months.
Patient: Oh really?
Doctor: Yes. But first, I want to congratulate you -- you've lost 3 kg since your last
visit. That's wonderful!
Doctor: I'm sure you are. And your HbA1c is now down to 6.4%, or 46 mmol/mol,
which is a huge improvement. It's great. How have you been doing in terms of
giving yourself the injection each day?
Patient: Oh, I got used to that very quickly. But I was feeling quite nauseous early
on.
Doctor: Yes, that's not at all unusual with this medication. Are you still experiencing
any nausea?
Doctor: Good -- that's quite typical. Your blood pressure is okay -- 135 over 85 mm
Hg -- and your LDL-C is much better. It’s down to 1.8 mmol/L, or 70 mg/dL, and
I'm very happy with that.
Doctor: You've done really well over the last few months. But please don't let up -
- you need to continue with the improvements that you've made with your diet, as
well as carrying on the exercise regularly.
Patient: Alright.
Doctor: I think you should continue the medications as they are, and I don't think I
need to see you again for about 3 months.
What is the best strategy for reducing the incidence of nausea in patients who are
starting therapy with a GLP-1 RA?
The changes in therapy introduced during the last visit have resulted in
substantial improvements for this patient. With the addition of the GLP-1 RA,
liraglutide, the patient's HbA1c has been reduced and is now on target. In addition,
the patient has lost more weight.
The underlying mechanisms that mediate the weight-reducing effects of
liraglutide are not clear, but are likely a combination of effects on the
gastrointestinal (GI) tract and the brain. Decreased appetite and increased satiety
are components.[23]
People with T2DM, particularly those with evidence of CVD, are at high
risk for chronic kidney disease. Multiple CV outcomes trials, which I have
previously mentioned, have demonstrated improvements in cardio-renal outcomes
in patients with T2DM and high CV risk.
Since Sarah is at high risk for another CV event, CV risk factor management
is critical to her care. Which of the following CV risk factor goals/targets of therapy
is most appropriate for Sarah?
Sarah has a longer life expectancy but has had a relatively long duration of
T2DM (8 years) and is taking multiple glucose-lowering medications. According
to the American Diabetes Association (ADA)/European Association for the Study
of Diabetes (EASD), the most appropriate HbA1c target for her would be <7.0%
(53 mmol/mol). The most recent ADA guidelines recommend a target blood
pressure (BP) of <140/90 mm Hg, although the ADA guidelines also have a
recommendation for a goal BP of <130/80 mm Hg in patients with T2DM and high
risk for CV disease (CVD), if the targets can be achieved "without undue treatment
burden." In patients at very high CV risk, such as Sarah, with documented CVD, an
LDL-C goal of <1.8 mmol/L (70 mg/dL) or a reduction of at least 50% from
baseline is recommended.
Question 2 of 5
At the time of her initial visit, Sarah was taking metformin 1000 mg twice
daily and glipizide 5 mg four times daily. Her physician recommended adding a
dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin 100 mg once daily, to her
antihyperglycemic regimen. After 6 weeks of sitagliptin therapy, Sarah's HbA1c
decreased from 8.5% to 7.8%.
A. I would not make a change at this time, but would have the patient return in
3 months to recheck her HbA1c
B. Increase glipizide to 10 mg four times daily
C. Switch glipizide 5 mg four times daily to extended-release glipizide 20 mg
once daily
D. Discontinue glipizide and sitagliptin and add a glucagon-like peptide-1
receptor agonist (GLP-1 RA) or sodium-glucose cotransporter 2
(SGLT2) inhibitor
Question 3 of 5
What is the best strategy for reducing the incidence of nausea in patients who are
starting therapy with a GLP-1 RA?
A. Liraglutide only