Risk Reduction in Cardiovascular Patients: Beyond Lipids
Risk Reduction in the
Cardiovascular Patient: Outside
of Lipids
Dine and Learn Nov 30, 2022
Dr. Jenny Rajala
Faculty/Presenter Disclosure
•
Faculty:
Dr. Jennifer Rajala
•
Relationships with financial sponsors:
•
Any direct financial relationships including receipt of honoraria:
Pfizer, Bayer, Boehringer-
Ingelheim, CardioMetabolic Collaborative Clinic
•
Memberships on advisory boards or speakers’ bureau: Nil
•
Patents for drugs or devices
: Nil
•
Other: financial relationships/investments
Nil
CFPC CoI Templates: Slide 1 – used in Faculty presentation only.
Disclosure of Financial Support
•
This program has received financial support from
the South Island Division of Family Practice
in
the form of
an educational grant
•
Potential for conflict(s) of interest
:
•
Dr. Jennifer Rajala
has received
payment
from
Doctors of BC for this session
AND
previously received
payments from Bayer for prior talks about medications that will be discussed tonight.
CFPC CoI Templates: Slide 2
Mitigating Potential Bias
•
The talk involves generic medications wherever possible
•
Use of randomized trials and meta-analysis where possible to guide decisions
•
Use of guidelines where appropriate
CFPC CoI Templates: Slide 3
Kathy
•
72F
•
Prior multivessel PCI for 3 separate NSTEMIs
over the past 8 years
•
Carotid endarterectomy 5 years ago
•
2 block claudication
•
HTN
•
Type 2 diabetes mellitus, HbA1c 7.8%
•
Dyslipidemia, non-HDL controlled at 2.1
•
Ex-smoker, quit 8 years ago
Medications:
Aspirin 81 mg daily
Ramipril 5 mg BID
Bisoprolol 2.5 mg daily
Chlorthalidone 25 mg daily
Atorvastatin 80 mg daily
Metformin 850 mg TID
Gliclazide 60 mg daily
On examination:
115/76, HR 65 bpm
Normal cardiac exam
Femoral bruits present
Aspirin
•
Primary prevention
•
Secondary prevention
•
Long term DAPT
•
Peri-operative management
Primary prevention
•
In meta-analysis of 10 RCTs of primary prevention the use of low dose
ASA was associated with:
•
MACE RR 0.89 (95% CI 0.84-0.93)
•
MI
RR 0.86 (95% CI 0.78-0.95)
•
Ischemic stroke RR 0.84 (95% CI 0.76-0.93)
•
Major bleeding RR 1.42 (95% CI 1.26-1.60)
•
Intracranial hemorrhage RR 1.33 (95% CI 1.11-1.59)
•
GI bleeding RR 1.91 (95% CI 1.44-2.54)
•
NNT for MACE: high risk 682, low risk 2191
•
NNH major bleeding: high risk 983, low risk 819
American Journal of Cardiovascular Drugs 2022; 22:657
Secondary Prevention
Lancet 2009;373(9678):1849
Figure 3
Long term DAPT
•
DAPT trial – 9961 pts with DES randomized to plavix or prasugrel and ASA
vs ASA alone during the period of 12-30 months post PCI
•
Stent thrombosis 0.4% in DAPT vs 1.4% SAPT (p<0.001)
•
MACE 4.3% DAPT vs 5.9% SAPT (p<0.001)
•
All cause death 2.0% DAPT vs 1.5% SAPT (p = 0.05)
•
Moderate or severe bleeding 2.5% DAPT vs 1.6% SAPT (p=0.001)
•
Pegasus- TIMI 54 trial – 21162 patients with MI to 1-3 years of ASA with
ticagrelor 90 mg BID, 60 mg BID or placebo
•
CV death, MI, or CVA in 7.85% tica 90 BID, 7.77% tica 60 BID, and 9.04% placebo (p =
0.004 for 90 BID dose and 0.008 for 60 BID dose vs placebo)
•
TIMI major bleeding 2.60% with 90 BID, 2.30% with 60 BID, and 1.06% with placebo
(p <0.001 for each dose vs placebo)
1. NEJM 2014; 371:2155
2. NEJM 2015; 372:1791
Long Term DAPT
•
Consider for patients who have a low bleeding risk and tolerate DAPT
for 1 year who have high risk clinical features for thrombotic events
CCS 2018 Antiplatelet Guidelines
Use of PPI in patients on DAPT
•
COGENT trial is largest trial thus far
•
Pts with indication for DAPT with clopidogrel and ASA to either omeprazole
or placebo
•
Primary CV end point was CV death, nonfatal MI, revasc, or stroke
•
Primary GI end point was overt or occult bleeding, symptomatic gastroduo
ulcers or erosions, obstruction or perforation.
•
3761 patients analyzed
•
GI events 1.1% with omeprazole vs 2.9% with placebo at 180 days (HR
0.34, 95% CI 0.18-0.63, P <0.001
•
CV end point 4.9% with omeprazole, 5.7% with placebo, HR 0.99, p 0.96
NEJM 2010; 363:1909
Use of PPI in patients on DAPT
•
ACC 2010 guidelines on NSTEMI, re-iterated in ACC 2016 focused
update on duration of antiplatelet therapy
•
Use PPI in patients with history of GI bleed on DAPT (class 1)
•
Consider PPI in patients with increased risk of GI bleeding who are on
DAPT (advanced age, warfarin, steroids, NSAIDS (Class 2)
SGLT2i and GLP-1 RA
Guidelines
•
Use of SGLT2i and GLP-1 RA have been incorporated into both
American Diabetes Association and ESC 2019 Guidelines on Diabetes,
Pre-Diabetes and CardioVascular disease
•
2022 Canadian Cardiovascular Society Guideline for Use of GLP-1
Receptor Antagonists and SGLT2 Inhibitors for Cardiorenal Risk
Reduction
Can J Cardiol 2022;38(8):1153
Can J Cardiol 2022;38(8):1153
Can J Cardiol 2022;38(8):1153
Vascular Protection Dose of Rivaroxaban
Dual Pathway Inhibition with Rivaroxaban Vascular Dose 2.5 mg bid +
ASA
Reduced CV Death, Stroke and MI
*Rates as at mean follow up of 23 months
Eikelboom JW
et al
.
N Engl J Med
2017; 377:1319-30
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5.4%
4.9%
4.1%
ARR for ASA vs Riva 2.5 BID + ASA = 1.3%
NNT = 77
Consistent Benefit of Dual Pathway Inhibition with Rivaroxaban
Vascular Dose 2.5 mg bid
+ ASA in CAD Patients with PAD
Favours rivaroxaban
2.5 mg bid + ASA
Favours
ASA alone
Connolly SJ et al. Lancet 2018;391:205–218.
NNT= 37
NNT= 37
NNH= 106
CCS 2022 Guidelines on Peripheral
Arterial Disease
In this presentation, Dr. Jenny Rajala delves into strategies for reducing cardiovascular risk beyond lipid management. The slides discuss various aspects including financial disclosures, conflict of interest mitigation, patient case studies, and the role of aspirin in primary prevention. Detailed insights on primary prevention efficacy and risk factors are provided based on meta-analyses and randomized trials.
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Presentation Transcript
Risk Reduction in the Cardiovascular Patient: Outside of Lipids Dine and Learn Nov 30, 2022 Dr. Jenny Rajala
CFPC CoI Templates: Slide 1 used in Faculty presentation only. Faculty/Presenter Disclosure Faculty: Dr. Jennifer Rajala Relationships with financial sponsors: Any direct financial relationships including receipt of honoraria: Pfizer, Bayer, Boehringer- Ingelheim, CardioMetabolic Collaborative Clinic Memberships on advisory boards or speakers bureau: Nil Patents for drugs or devices: Nil Other: financial relationships/investments Nil
CFPC CoI Templates: Slide 2 Disclosure of Financial Support This program has received financial support from the South Island Division of Family Practice in the form of an educational grant Potential for conflict(s) of interest: Dr. Jennifer Rajala has received payment from Doctors of BC for this session AND previously received payments from Bayer for prior talks about medications that will be discussed tonight.
CFPC CoI Templates: Slide 3 Mitigating Potential Bias The talk involves generic medications wherever possible Use of randomized trials and meta-analysis where possible to guide decisions Use of guidelines where appropriate
Kathy 72F Prior multivessel PCI for 3 separate NSTEMIs over the past 8 years Carotid endarterectomy 5 years ago 2 block claudication HTN Type 2 diabetes mellitus, HbA1c 7.8% Dyslipidemia, non-HDL controlled at 2.1 Ex-smoker, quit 8 years ago Medications: Aspirin 81 mg daily Ramipril 5 mg BID Bisoprolol 2.5 mg daily Chlorthalidone 25 mg daily Atorvastatin 80 mg daily Metformin 850 mg TID Gliclazide 60 mg daily On examination: 115/76, HR 65 bpm Normal cardiac exam Femoral bruits present
Aspirin Primary prevention Secondary prevention Long term DAPT Peri-operative management
Primary prevention In meta-analysis of 10 RCTs of primary prevention the use of low dose ASA was associated with: MACE RR 0.89 (95% CI 0.84-0.93) MI RR 0.86 (95% CI 0.78-0.95) Ischemic stroke RR 0.84 (95% CI 0.76-0.93) Major bleeding RR 1.42 (95% CI 1.26-1.60) Intracranial hemorrhage RR 1.33 (95% CI 1.11-1.59) GI bleeding RR 1.91 (95% CI 1.44-2.54) NNT for MACE: high risk 682, low risk 2191 NNH major bleeding: high risk 983, low risk 819 American Journal of Cardiovascular Drugs 2022; 22:657
Secondary Prevention Figure 3 Lancet 2009;373(9678):1849
Long term DAPT DAPT trial 9961 pts with DES randomized to plavix or prasugrel and ASA vs ASA alone during the period of 12-30 months post PCI Stent thrombosis 0.4% in DAPT vs 1.4% SAPT (p<0.001) MACE 4.3% DAPT vs 5.9% SAPT (p<0.001) All cause death 2.0% DAPT vs 1.5% SAPT (p = 0.05) Moderate or severe bleeding 2.5% DAPT vs 1.6% SAPT (p=0.001) Pegasus- TIMI 54 trial 21162 patients with MI to 1-3 years of ASA with ticagrelor 90 mg BID, 60 mg BID or placebo CV death, MI, or CVA in 7.85% tica 90 BID, 7.77% tica 60 BID, and 9.04% placebo (p = 0.004 for 90 BID dose and 0.008 for 60 BID dose vs placebo) TIMI major bleeding 2.60% with 90 BID, 2.30% with 60 BID, and 1.06% with placebo (p <0.001 for each dose vs placebo) 1. NEJM 2014; 371:2155 2. NEJM 2015; 372:1791
Long Term DAPT Consider for patients who have a low bleeding risk and tolerate DAPT for 1 year who have high risk clinical features for thrombotic events CCS 2018 Antiplatelet Guidelines
Guidelines Use of SGLT2i and GLP-1 RA have been incorporated into both American Diabetes Association and ESC 2019 Guidelines on Diabetes, Pre-Diabetes and CardioVascular disease 2022 Canadian Cardiovascular Society Guideline for Use of GLP-1 Receptor Antagonists and SGLT2 Inhibitors for Cardiorenal Risk Reduction Can J Cardiol 2022;38(8):1153
Dual Pathway Inhibition with Rivaroxaban Vascular Dose 2.5 mg bid + ASA Reduced CV Death, Stroke and MI 10 ASA 100mg od Rivaroxaban 5mg bid 5.4% Rivaroxaban 2.5mg bid + ASA 100mg od 8 4.9% Cumulative incidence (%) 4.1% ARR for ASA vs Riva 2.5 BID + ASA = 1.3% NNT = 77 6 4 MACE* % HR (95% CI) p-value 2 ASA 100mg OD 5.4 - - Rivaroxaban 5mg BID 4.9 0.90 (0.79-1.03) 0.12 Rivaroxaban 2.5mg BID + ASA 100 mg OD 4.1 0.76 (0.66-0.86) <0.001 0 0 1 2 3 Year Number at risk ASA 100mg od Riva 5mg bid Riva 2.5mg bid + ASA 100mg od 9126 9117 7808 7824 3860 3862 669 670 9152 7904 3912 658 *Rates as at mean follow up of 23 months Eikelboom JW et al. N Engl J Med 2017; 377:1319-30
Consistent Benefit of Dual Pathway Inhibition with Rivaroxaban Vascular Dose 2.5 mg bid + ASA in CAD Patients with PAD Rivaroxaban 2.5 mg bid + ASA n/N (%) p-value (intx) ASA alone n/N (%) ARR/ ARI Subgroup HR (95% CI) HR (95% CI) CV Death, Stroke or MI Peripheral artery disease Yes No NNT= 37 0.37 ARR 2.73 1.06 94/1656 253/6657 (5.7) (4) 138/1641 322/6620 (8.4) (5) 0.67 (0.52-0.87) 0.77 (0.66-0.91) Major Bleeding Peripheral artery disease Yes No NNH= 106 0.46 ARI 0.95 1.33 52/1656 211/6657 (3) (3) 36/1641 122/6620 (2) (2) 1.43 (0.93-2.19) 1.73 (1.38-2.16) Net Clinical Benefit Peripheral artery disease Yes No NNT= 37 0.24 101/1656 291/6657 (6) (4) 145/1641 349/6620 (9) (5) 0.68 (0.53-0.88) 0.82 (0.71-0.96) 0.1 1 10 Favours ASA alone Favours rivaroxaban 2.5 mg bid + ASA Connolly SJ et al. Lancet 2018;391:205 218.
CCS 2022 Guidelines on Peripheral Arterial Disease
