Moderne Strategie di Prevenzione Cardiovascolare Come ottimizzare i benefici della terapia con statine G. Paolo Reboldi

Moderne Strategie di Prevenzione Cardiovascolare

“Come ottimizzare i benefici della terapia con statine”

G. Paolo Reboldi

ESC 2007: Fourth Joint Task Force Recommendations

Three strategies for the prevention of CVD can be distinguished: population, high-risk secondary prevention

The three strategies are necessary and complement each other.

Prevention strategies and policy issues

European Journal of Cardiovascular Prevention and Rehabilitation 2007, 14(Supp 2):E1–E40


To prevent one single cardiovascular event, it will be necessary to intervene in many subjects with no apparent benefit to them (prevention paradox).

The number of subjects in whom an intervention is needed to prevent one case will vary in different populations or population subgroups (e.g in women) depending on their underlying prevalences and distribution of risk factors, and the incidence rate of disease.




Those with: known CVD; type 2 diabetes or type 1 diabetes with microalbuminuria; very high levels of individual risk factors.

are already at INCREASED CVD RISK and need management of all risk factors.

For all other people, the SCORE risk charts can be used to estimate total risk

This is critically important because many people have mildly raised levels of several risk factors that, in combination, can result in unexpectedly high levels of total CVD risk.

How do I assess CVD risk quickly and easily?





The prevention paradox:high risk individuals gain most from preventive measures, but most CVD deaths come from apparently low risk subjects because they are so numerous.




The prevention paradox: most CVD deaths come from apparently low risk subjects



Relative risk reductions seem to be constant at all lipid levels, but absolute risk reductions are small in those with low lipid levels, with little evidence of a reduction in total mortality.

The universal use of statins may be unrealistic in some economies

Should statins be given to all?


Il piano di costo-efficacia

Statine in pazienti ad

Alto Rischio CV

DominanteDominante

Effetti Effetti maggiorimaggiori

Costi Costi minoriminori

Effetti Effetti minoriminori

Costi Costi maggiorimaggiori

WTPWTP

Questionabile

Inaccettabile

PotenzialmenPotenzialmenteteVantaggiosoVantaggioso

Statine in pazienti a

Basso Rischio CV WTPWTP

WTPWTP

Cost effectiveness of statins per categories of absolute risk.Centiles and median refer to the distribution of published costeffectiveness ratio per category of absolute risk

Franco OH J. Epidemiol. Community Health 2005;59;927-933

Questionable cost-effectiveness of statins for primary prevention of cardiovascular events

Messori A et al BMJ. 2003 Oct 4;327(7418):808-9

Effect of annual statin cost on cost-effectiveness for the combination of aspirin and a statin versus aspirin alone.

Statin cost is expressed in 2003 dollars. Base-case value is shown with the dotted vertical line.

Primary Prevention of Coronary Heart Disease Events in Men

Pignone at al Ann Intern Med. 2006;144:326-336

Ganz, D. A. et. al. Ann Intern Med 2000;132:780-787

Combined Risk reduction by statins (fatal MI, nonfatal MI and stroke) Vs. CERs

Expensive Intervention ($ 2000/y)

CheapIntervention ($ 250/y) Paying for an expensive

intervention is convenient only if the benefit is great.Paying for a cheapIntervention is convenient also if the benefit is small !!

Use of different statins in European countries in 2000

0 20 40 60 80

Italy

Denmark

Portugal

Austria

UK

Spain

Germany

Finland

Sweden

Belgium

Netherlands

France

Norway

0 200 400 600 800 1000

Denmark

Portugal

Finland

Austria

Norway

Sweden

Belgium

Netherlands

Italy

Spain

UK

Germany

France

Total use in million defined daily doses.Rate use in defined daily doses/1000

of population covered/day.

Walley et al BMJ 2004;328;385-386

Statine, andamento temporale del consumo territoriale di classe A-SSN (2000-2006)

Prevalenza d’uso di farmaci nei pazienti con ipertensione ed ipertensione + diabete con o senza eventi CV

% di pazienti che hanno usato almeno una volta nel corso del 2006 una delle categorie terapeutiche

Prevalenza d’uso e durata del trattamento nei pazienti con ipertensione ed ipertensione + diabete con o senza eventi CV

Statine, distribuzione in quartili del consumo territoriale 2006 di classe A-SSN (DDD/1000 abitanti die pesate)

Statine, distribuzione in quartili del consumo territoriale 2006 di classe A-SSN (DDD/1000 abitanti die pesate)

84%

61%59% 60%

92%

75%73%

68%

49%

80%

61%

75%

>70%

>85%>85%

>90%

40%

50%

60%

70%

80%

90%

100%

ASA Beta-bloccanti

ACE-inibitori

Statine

Blitz-1 Blitz-2 In-ACS Outcome Obiettivo CCORT/CCS

Terapie Dimissione per SCA:Registri Italiani vs. Standard CCORT/CCS

Casella G, et al. G Ital Ital Cardiol 2006; 7: 176-185 – Centro Studi ANMCO In-ACS Outcome, Data on File

Gli standard di qualità CCORT/CCS, elaborati dalla società canadese di cardiologia, rappresentano la percentuale minima di pazienti ideali che dovrebbero ricevere il trattamento raccomandato.

Adherence to chronic cardiovascular therapies: persistence over the years and dose coverage

Rates of persistence and coverage in 32068 patientsAnalysis of GPs Prescription in Ravenna, Italy

(diamonds, persistence; bars, coverage)

Poluzzi E et al Br J Clin Pharmacol 63:3 346–355 346

Patients were defined as persistent when they received at least one prescription of any agent of the considered therapeutic category in 2000, 2001 and 2002.

Patients were defined as covered when the amount of drugs of the same category received during each of the 3 years of the study was consistent with a daily treatment. To this purpose, we identified the minimal daily dose recommended for maintenance therapy for each drug and calculated the total number of minimal doses of each agent received, by the patient, year by year. Patients reaching at least 300 minimal doses per year were considered as covered, allowing a tolerance of 20% over the 365-day period

New patients on treatment Patients already on treatment

Adherence to chronic cardiovascular therapies: persistence over the years and dose coverage

Percentage of 3-year coverage and ORs among patients already on treatment, in the presence of combined

therapy with other drug categories.

Poluzzi E et al Br J Clin Pharmacol 63:3 346–355 346

20 25 22 24

1.13

0.62

0.83

1.48

1.9

1.29

1.06

1.26

1.8

Ref

00.20.40.60.8

11.21.41.61.8

2

LLDs Alone With AHAs With OHAs With AHAsand OHAs

OR

an

d 9

5%

CIs

05101520253035404550

% C

ov

era

ge

LLD=Lipid Lowering Drugs AHA= Anti-hypertensive Agents OHA=Oral hypoglycemic Agents

Prescription of lipid lowering agents and time from the acute event

37% 38%33%

27%

0%

5%

10%

15%

20%

25%

30%

35%

40%

< 3 3–5 6–10 > 10

Years from Acute Event

Lipid-lowering agents

P < 0.001

Italian General Practitioners Database; 3588 patients (mean age 68.7), with an average time from event of 6 years.

Filippi et al Journal of Cardiovascular Medicine 2006, 7:422–426

Relationship Between Adherence to Evidence-Based Pharmacotherapy and Long-term Mortality After Acute Myocardial Infarction

Kaplan-Meier Estimates of Time to Death for Statin Users According to Adherence Level

Rasmussen et al. JAMA. 2007;297:177-186.

High (PDC ≥80%)Intermediate (PDC 40%-79%) Low (PDC <40%)PDC Proportion of Days Covered

AdjustedHazard Ratio

Low vs High 1.25 (1.09-1.42);P=.001

Int. vs High 1.121.01-1.25;P=.03

Self-reported Medication Adherence and Cardiovascular Events in Patients With Stable Coronary Heart Disease: The Heart and Soul Study

Proportion surviving without a cardiovascular event (myocardial infarction, stroke or coronary heart disease death) by self-reported medication adherence at baseline, adjusted for age, sex, race, educational level, smoking, diabetes mellitus, hypertension, depressive symptoms, number of cardiovascular medications, use of -blocker, use of statin, left ventricular ejection fraction, weekly angina, high-density lipoprotein cholesterol level and low-density lipoprotein cholesterol level (P = .006).

Gehi et al Arch Intern Med. 2007;167:1798-1803

Adherent> 75%

in the past month

Non-Adherent≤ 75%

in the past month

Clinical Crossroads: A 63-Year-Old Man With Multiple Cardiovascular Risk Factors and Poor Adherence to Treatment Plans

Mr P has long-standing hypertension, obesity, and diabetes mellitus and has experienced life-threatening cardiovascular events.

Mr P is receiving evidence-based clinical care but has adhered to his medical regimen poorly and remains at considerable risk of future catastrophic cardiovascular events.

He has been prescribed many medications, including, aspirin, atenolol, lisinopril, amlodipine atorvastatin, furosemide, glyburide, metformin, insulin, and allopurinol

Bodenheimer T JAMA. 2007;298(17):2048-2055


Although Mr P was cared for using evidence-based medicine, it appears that for Mr P, evidence-based medicine failed.

Mr P's blood pressure was uncontrolled during visits in 2001, 2003, 2004, and 2006. His body mass index hovered around 38, well above the obesity threshold of 30. Between 2004 and 2006, his hemoglobin A1c level fluctuated between 5% and 8.8%. His total cholesterol level rose from 132 mg/dL (3.42 mmol/L) in 2004 to 256 mg/dL (6.63 mmol/L) in 2005

Why Does Evidence-Based Medicine Often Fail?



Step 1: Research uncovers the evidence.

Step 2: Clinicians learn the evidence. Step 3: Clinicians use the evidence at

every visit for every patient. Step 4: Clinicians make sure that

patients understand the evidence. Step 5: Clinicians assist and

encourage patients to incorporate the evidence into their lives.


Practicing evidence-based medicine should be a 5-step process:


Step 3: Use the evidence! only 55% of patients received recommended care.N Engl J Med. 2003;348(26):2635-2645

Step 4: Patients must understand!Less than 50% of patients leave an office visit not understanding what they were told by the physician.Agency for Healthcare Research and Quality; 2005

Step 5: Assist and encourage patients!patients participated in medical decisions only 9% of the tim, 96% wanted to be offered choices and to be asked their opinionMed Care. 2005;43(10):960-969


How Is the US Health Care System Performing on Steps 3, 4, and 5?

Challenges for improving medication adherence

Patient characteristics: advanced age, cognitive impairment, depression, attitudes and beliefs about the importance of medications, the disease being treated and the potential for adverse effects.

Barriers to adherence: adverse effects, polypharmacy, frequent dosing and high cost.

System and Clinician related barriers: insufficient access to physicians, lack of trust between clinician and patient, physician’s negative attitude to the value of guideline-recommended care.

Simpson R JAMA 2006; 296: 2614-2616

CCUCCU

Acute Acute CareCare

Chronic Chronic CareCare

Secondary Secondary PreventionPrevention

Transition From Acute to Long-term Management

X

EBM basedEBM basedpracticepractice

EBM basedEBM basedpracticepractice

Competenzaclinica

personale

Preferenze delpaziente

Evidenze dellaricerca

Competenzaclinica

personale

Preferenze delpaziente

Evidenze dellaricerca A bridge over troubled waters…

X

Team medicopreparato,

attivoe propositivo

Interazioniproduttive

Esiti clinici e funzionaliEsiti clinici e funzionali

Sistema Sanitario

Risorse e Politiche

Comunità Comunità Organizzazione dell’assistenza sanitaria

Disease Management

Chronic Care Model

Pazienteattivo

e informato

Autogestione “empowerment” Piano di

erogazionedei servizi

SistemiInformativi

CliniciAnalisiDecisionale

EBM

Modificata da: Bodenheimer et al JAMA. 2002 Oct 16;288(15):1909-14

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Moderne Strategie di Prevenzione Cardiovascolare Come ottimizzare i benefici della terapia con statine G. Paolo Reboldi