Prevention and Management of Cardiovascular Disease in Primary Care: A Comment on the PEER Simplified Lipid Guideline

Abstract

Background

In Canada, 2 guidelines provide guidance for the management of dyslipidemia. The Patients, Experience, Evidence, Research simplified lipid guidelines, intended for primary care practitioners, and the Canadian Cardiovascular Society guidelines, intended for all practitioners, are based on differing methodologies with distinct priorities and preferences. The disparate approaches may contribute to confusion among family practitioners and their co-managed patients, with the potential for compromised care, differing standards for training in the fundamentals of lipidology, and differing criteria that might be used in practice audits to evaluate quality of care.

Methods

The Patients, Experience, Evidence, Research (PEER) recommendations were considered by primary authors of the Canadian Cardiovascular Society guideline to identify areas of concordance, discordance, or agreement with qualifications.

Results

Discordance between the guidelines is greatest with respect to interpretation of the cholesterol profile, the implications of elevated triglyceride, the utility of apolipoprotein B and non-high-density lipoprotein-cholesterol measurements, the role of nonstatin medications, and the importance of assuring adherence and avoiding undertreatment through follow-up measurement of lipid profiles. The disparate importance attached to identification of patients with enhanced risk due to an elevated lipoprotein (a) level is also apparent.

Conclusions

This comparison attempts to reconcile key principles of practice, to foster both high quality of care and fully informed patient-centred decision-making.

Everything should be made as simple as possible, but not simpler.

—concept attributed to Albert Einstein by Roger Sessions and Louis Zukofsky

The simplified lipid guidelines from Patients, Experience, Evidence, Research (PEER) were updated in 2023.¹ These were intended for primary care practitioners and specifically exclude lipid issues pertaining to pediatrics, pregnant or lactating patients, and patients with familial hypercholesterolemia (FH). Similarly, atherosclerotic cardiovascular (CV) disease prevention strategies beyond lipid-lowering therapies were identified as lying beyond the scope of the guidelines. The PEER recommendations were based not on primary evidence, but rather on a systematic review of systematic reviews of 7 different classes of lipid-lowering medications: statins; ezetimibe; proprotein convertase subtilisin/kexin type 9 inhibitors; fibrates; bile acid sequestrants; niacin; and omega-3 supplements (eicosapentaenoic acid + docosahexaenoic acid, or icosapent ethyl). The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework tables for assessment of the quality of these reviews were not provided. An additional 11, supplemental, clinical questions were explored using a “rapid review process.” This guideline places emphasis on major adverse cardiovascular events (MACE), CV mortality, and all-cause mortality as the main goal of lipid-lowering therapy.

The simplified guideline is a laudable exercise, designed primarily “with the needs of family physicians and other primary care providers in mind” and with consideration of patient preferences. The guideline also is influenced by the “time needed to treat” principle, which is a direct and understandable manifestation of the well-acknowledged pressures in family practice to deal with many competing demands. To avoid bias, the process involved only authors with no conflicts of interest with the pharmaceutical industry, but they did not identify any participant(s) with expertise in the field of dyslipidemia, which normally is considered a part of a “team approach” for cases that may not be completely routine in nature.

The process leading to the Canadian Cardiovascular Society (CCS) guidelines is reported in detail; it included a diversity of professional (medicine, nursing, pharmacology) and practice expertise (lipids, endocrinology, cardiology, general internal medicine, family medicine, nutritional science, cardiometabolic risk, and women’s CV health).^2,3 The process also included review and representation from the Canadian Society of Internal Medicine, the College of Family Physicians of Canada, and the Canadian Pharmacists Association. An important point to note is that, although authors with conflicts of interest with the pharmaceutical industry were not excluded, not all authors had conflicts, and those who did have them declared them and were excluded from voting on any recommendations pertaining to the reported conflicts.

The impact of having 2 sets of national guidelines based on differing methodologies, with distinct priorities and preferences, creates concern among those of us who routinely co-manage patients with primary care physicians and who are called upon to provide education in the field of lipid-related CV risk reduction. The disparate approaches contribute to confusion among family practitioners and their co-managed patients, with the potential for compromised care. The standards for training in the fundamentals of lipidology are now quite discordant. Criteria indicating quality of care in practice audits also might be quite disparate. Although providing succinct guidance for routine and uncomplicated cases in the general population is commedable, many more nuanced issues affect individuals, including those with FH. Some of these issues, addressed by the CCS guidelines, are minimized by the PEER guidelines as not merely being beyond their scope but also having a potentially low level of importance. Given that optimal patient outcomes are the top priority for all practitioners and guidelines, whether patients who do not fulfill the basic lipid scenarios encompassed by the PEER simplified approach would receive the benefit of the full discussion needed to inform decision-making in accordance with their personal health priorities is unclear.

The purpose of this overview is to juxtapose the recommendations in the latest PEER guidelines with the principles and perspectives contained within the CCS lipid guidelines, to identify areas of concordance and discordance. We organize the overview according to the major categories described in the PEER guidelines, as follows: screening and testing (Fig. 1, A and B)⁴; interventions (Fig. 2, A and B)^5,6; considerations in patients older than 75 years (Fig. 3)⁷; statin intolerance (Fig. 4); and follow-up (Fig. 5). Each figure is stratified by identifying strong recommendations (ie, “actual recommendations”) and weak recommendations (ie, “suggestions”), which were the same conventions as those adopted in the PEER guidelines. We have colour-coded areas of substantial agreement (green), disagreement (red), and agreement with qualifications (yellow), for ease of display.

Figure 1.

Shown are screening and testing. Recommendations from the Patients, Experience, Evidence, Research (PEER) guidelines are highlighted in (A) gray (weak recommendations) and (B) white (strong recommendations). The Canadian Cardiovascular Society (CCS) guidelines perspective is summarized in the last column and is colour-coded to convey strong similarities (green), similarities but with important additional factors outlined in the CCS guidelines (yellow), and discordances (red). apoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; CV, cardiovascular; CVD, cardiovascular disease; FH, familial hypercholesterolemia; HDL-C, high-density lipoprotein; IPE, icosapent ethyl; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); PCSK9, proprotein convertase subtilisin/kexin type 9; RCT, randomized controlled trial; TG, triglyceride.

Figure 2.

Shown are interventions. Recommendations from the Patients, Experience, Evidence, Research (PEER) guidelines are highlighted in (A) gray (weak recommendations) and (B) white (strong recommendations). The Canadian Cardiovascular Society (CCS) guidelines perspective is summarized in the last column and is colour-coded to convey strong similarities (green), similarities but with important additional factors outlined in the CCS guidelines (yellow), and discordances (red). apoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; CVD, cardiovascular disease; DASH, dietary approaches to stop hypertension; FH, familial hypercholesterolemia; HDL-C, high-density lipoprotein; IMPROVE-IT trial, Improved Reduction of Outcomes: Vytorin Efficacy International Trial; IPE, icosapent ethyl; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; RCT, randomized controlled trial; TG, triglyceride; T2D, type 2 diabetes

Figure 3.

Shown are considerations in patients aged > 75 years. Recommendations from the Patients, Experience, Evidence, Research (PEER) guidelines are highlighted in gray (weak recommendations) and white (strong recommendations). The Canadian Cardiovascular Society (CCS) guidelines perspective is summarized in the last column and is colour-coded to convey strong similarities (green), and similarities but with important additional factors outlined in the CCS guidelines (yellow). Note that 2 of the recommendations from PEER are not captured by the current CCS guideline; these are highlighted in white. CV, cardiovascular; CVD, CV disease; PROSPER trial, Prospective Study of Pravastatin in the Elderly at Risk.

Figure 4.

Shown is statin intolerance. Recommendations from the Patients, Experience, Evidence, Research (PEER) guidelines are highlighted in gray (weak recommendations) and white (strong recommendations). The Canadian Cardiovascular Society (CCS) guidelines perspective is summarized in the last column and is colour-coded to convey strong similarities (green), and discordances (red). ALT, alanine transaminase; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; CV, cardiovascular; DASH, dietary approaches to stop hypertension; IPE, icosapent ethyl; LDL-C, low-density lipoprotein cholesterol; LFT, liver function testing; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; TG, triglyceride.

Figure 5.

Shown is follow-up. Recommendations from the Patients, Experience, Evidence, Research (PEER) guidelines are highlighted in gray (weak recommendations) and white (strong recommendations). The Canadian Cardiovascular Society (CCS) guidelines perspective is summarized in the last column and is colour-coded to convey similarities but with important additional factors outlined in the CCS guidelines (yellow), and discordances (red). ALT, alanine transaminase; Apo B, apolipoprotein B; CK, creatinine kinase; CV, cardiovascular; HDL-C, LFT, liver function testing; RCT, randomized controlled trial; TG, triglyceride.

Figure 1B (screening and testing) highlights several major conceptual discordances, namely ignoring the importance of understanding the limitations of the basic cholesterol profile—particularly when the triglyceride level is abnormal—the limitations of a focus solely on low-density lipoprotein cholesterol (LDL-C), and the useful role of apolipoprotein B (and non-high-density lipoprotein cholesterol to some extent) in overcoming these limitations, to avoid undertreatment. Additionally, the PEER guidelines ignore the importance of the amplification of atherosclerotic CV disease risk in the presence of elevated levels of lipoprotein (a). This marker of risk cannot be detected without direct measurement. When the level is elevated, earlier and more-aggressive cholesterol and other risk-factor management is recommended. As lipoprotien (a) is determined largely genetically, and given that the PEER guideline already excludes consideration of FH, we believe that both of these syndromes should be identified by the general practitioner and either treated according to the CCS guidelines or assessed through referral when it is available.

Figure 2A underscores that additional lowering of LDL-C level using ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitors is distinct from the lowering of CV risk with icosapent ethyl, which does not lower LDL-C level but has been shown to reduce CV risk in patients on statin with a residually elevated triglyceride level in secondary prevention, and in primary prevention for patients with type 2 diabetes and additional risk factors. Figure 2B (Interventions) also demonstrates a major discordance and misconception regarding the utility of nonstatin therapies, including agents such as ezetimibe, which many primary care physicians utilize routinely when it is warranted. Furthermore, the lack of endorsement of nonstatin therapies is also problematic when dealing with statin intolerance (Fig. 4) that may require nonstatins to adequately control cholesterol-mediated risk. Also evident is a misconception regarding use of fibrates, which have not been shown to reduce CV risk in patients on statins. Finally, the PEER guideline makes a strong recommendation against follow-up testing of lipids after initiation of statin therapy (Fig. 5). This recommendation means that assessment of adherence is not optimal, and that adequacy of therapy, either through alteration of dosing or supplementation with nonstatin medications, is never addressed.

In consideration of the differences between the guidelines, we identify patient scenarios and opportunities for reconciliation, including the option to involve specialists in care of more complex or nuanced patient situations (Table 1).

Table 1.

Practical implications for scenarios that fall outside the scope of practice, as defined by the Patients, Experience, Evidence, Research (PEER) guidelines

Out-of-scope scenarios defined by PEER guidelines	Practical implications
Patients with familial hypercholesterolemia (or other genetic dyslipidemias), pediatric patients, and pregnant or lactating women	Implicit in the PEER guidelines is the idea that such situations either are managed according to other guidelines or specialist care is requested. Specialist care may not be available in all circumstances, and even when it is available, it may not be feasible for all patients, given the frequency of these situations.
	Elevated Lp(a) level, largely reflecting genetic inheritance, is a common and independent lipid risk marker that amplifies CV risk.
	The lipid-specialist community would welcome help in the case-finding and management of genetic dyslipidemia. Patients with FH and/or elevated Lp(a) level warrant cascade screening and longitudinal follow-up, both of which could be provided in primary care settings or, when available, through team management involving a specialist.
Patients unable to achieve goals with maximally tolerated statins due to either intolerance or lack of adequate lowering of LDL-C level	Nonstatin therapies, currently ezetimibe and PCSK9 inhibitors in Canada, as adjuncts to maximally tolerated statins, may be indicated when appropriate to overcome this important practice challenge, and specialist or other health-practitioner assistance with access to these medications (PCSK9 inhibitors) may be considered.
Patients on statins with a post-treatment TG level ≥ 1.5 mmol/L, irrespective of achieving LDL-C goals and/or thresholds	Understanding the simple concept of non-HDL-C or appreciating the value of apoB measurement for optimal interpretation of this common cholesterol profile are both practical steps and will avoid undertreatment of at-risk patients.
	Such patients with high-risk T2D or ASCVD may achieve additional CV risk reduction with use of IPE.
Patients meeting the criteria for statin therapy for primary prevention but who are unwilling to accept the primary care team’s recommendation for statin therapy	A full discussion of nontraditional risk factors, including, for example, coronary artery calcium scoring, Lp(a), apoB, etc. may be useful to inform a patient-physician discussion to address this practice challenge.
Patients aged > 75 y who desire a complete patient-physician discussion about personal CV risk	Such self-identified patients should be afforded an opportunity to develop a patient-centred health strategy compatible with their own preferences and priorities.
Patients with a TG level ≥ 10 mmol/L or patients with initial or recurrent pancreatitis with elevated TG level when gallstones, uncontrolled diabetes, or alcoholism are not present	Familiarity with the use of fibrates and/or emerging therapies is warranted to address this rare but serious practice challenge.

apoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; CV, cardiovascular; FH, familial hypercholesterolemia; HDL-C, high-density lipoprotein cholesterol; IPE, icosapent ethyl; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); PCSK9, proprotein convertase subtilisin/kexin type 9; TG, triglyceride; T2D, type 2 diabetes.

Conclusion

Primary care physicians certainly can constrain their scope of practice with respect to basic management of dyslipidemia, by following the PEER guidelines. This commentary is meant to provide a supplementary perspective to allow primary care physicians to also consider the full scope of knowledge in this rapidly evolving field, including the full range of existing and emerging diagnostic measures and therapeutic options that could be considered to ensure the optimal level of dyslipidemia management as endorsed by the CCS guidelines. Moreover, some family practitioners have already expanded or may wish to further expand their scope beyond the PEER guidelines. Regardless, all patients must be encouraged, in the context of full disclosure, to express their personal priorities and understand the range of recommended options for risk assessment and optimal therapy of dyslipidemia. Armed with this understanding, some patients may be satisfied with basic management, whereas others may prefer or indeed warrant referral to a specialist when that is feasible and appropriate. In all instances, of paramount importance is that patients be fully informed, so that tailored, patient-centred, and team-oriented care can be offered that includes options spanning basic care to optimal and individualized management strategies for CV risk reduction.