Factors Involved in Poor Control of Risk Factors

Transcription

1 Factors Involved in Poor Control of Risk Factors Patient compliance Clinical inertia Health Care System structure M

2 Limitations of Formal Studies Selection of patients Recruitment and follow-up alter patients natural behaviour M

3 Administrative Data-bases (Lombardy) Archives of residents receiving NHS assistance (demographic / administrative data) Hospitalizations in public / private hospitals with corresponding diagnosis (code) Outpatients drug prescriptions reimbursable by NHS M

4 Assessment of Compliance to Treatment Percent of time covered by drug prescription Discontinuation, i.e. lack of renewal of drug prescription over 9 (or 3 or 18) days following expiration of the previous prescription M

5 NHS Data-bases - Limitations Some drugs (e.g. antihypertensives) prescribed for a variety of diseases Clinical information limited Adjustment for confounders limited (age / gender / cotreatments / comorbidities / hospitalized events) Data from class C (not life-saving) drugs not available Data from class A (life-saving) drugs paid by patients not available Pre-farmacy loss of prescription not quantified Adherence assumed from drug possession M

6 NHS Data-bases - Potentials Real life setting Huge number of patients / Virtually all citizenship Territorial comparisons (countries / regions / local municipalities etc) Temporal comparisons Relationship of prescription patterns with events (hospitalizations) Data analyzed according to a variety of patient-related / other variables Large-scale information on drug effectiveness / safety M

7 Incidence of Modification of Initial Antihypertensive Monotherapy over 5 Years in Newly Treated Hypertensives with multiple prescriptions ( n = )) Cumulative incidence Discontinuation Combining Switching Months since starting antihypertensive treatment M Corrao, Zambon, Parodi, Poluzzi, Baldi, Merlino, Cesana, Mancia, J Hypertens 28; 26:

8 Percent of Patients With or Without Treatment Discontinuation or at Different Levels of Adherence to Drug Treatment (n = ) 8 Discontinuation Yes* No 25% 26% to % Adherence (days covered by prescription) 51% to 75% > 75% 6 % * At least 1 episode of no prescription coverage for > 9 days M Corrao, Parodi, Nicotra, Zambon, Merlino, Cesana, Mancia, J Hypert 211; 29:

9 Effects of Persistence or Adherence with Antihypertensive Drug Therapy on the Reduction in Hazard Ratio of Coronary (n = 6665) and Cerebrovascular (n = 5351) Outcomes in Patients Persistence category Adherence level Discontinuing use* (reference) Continuing use Very low (reference) Low Intermediate High Hazard ratio reduction (%) % -36% Coronary events -16% -21% -24% -23% -5-5 Cerebrovascular events Estimates are adjusted for gender, age, initial antihypertensive regimen, number of different classes of antihypertensive medications dispensed during FU, use of other drugs during FU, and categories of Charlson comorbidity index score. * At least 1 episode of no prescription coverage for > 9 days M Corrao, Parodi, Nicotra, Zambon, Merlino, Cesana, Mancia, J Hypert 211; 29:

10 Adherence to Statin Treatment in Lombardy Data-base (n = 9832 / 22-27) % 4.4% 3 % of patients % 2.8% 19.6% 1 Time covered by prescription 25% Very low 26-5% Low 51-75% Intermediate > 75% High M Corrao, Conti, Merlino, Catapano, Mancia, Clin Ther 21; 32: 3-31

11 Association between Adherence to Statin Therapy and Risk of IHD in Residents of Lombardy (Eliglible Participants 9832 / FU 22-27) Adherence level Hazard ratio * Very low ( 25%) Low (26-5%) Intermediate (51-75%) High (> 75%) ( ).82 ( ).81 ( ) * Adjusted for sex / age / statin type / switching among statins / concomitant use of other drugs / Charlson comorbidity score Proportion of drugs covered 1545 M Corrao, Conti, Merlino, Catapano, Mancia, Clin Therap 21; 32: 3

12 Risk of IHD (Hospital Diagnosis) in Patients Treated with Statin (n = ) Months with drug available HR HR (95% CI) < ( ).87 ( ).75 ( ).75 ( ) P for trend = M Corrao, Conti, Catapano, Merlino, Mancia, Clin Therap 21; 32: 3

13 The case of extremely low adherence to treatment Treatment discontinuation after 1st prescription 1764 M

14 Proportion of Patients Discontinuing Treatment after One Prescription vs Those with Two or More Prescriptions Antidiabetic drugs (n = 23,32) 37.2 Lipid lowering drugs (n = 16,4) 35.7 Antihypertensive drugs (n = 23,32) 35.6 % 2% 4% 6% 8% 1% > 2 prescriptions 1 prescription 1669 M Corrao,Zambon,Parodi,Merlino, Mancia, Am J Hypert, 212,25,549

15 Lombardy Data-base and Discontinuation of Treatment More than one third of patients discontinue antihypertensive, lipid lowering and antidiabetic treatment after the initial prescription Was initial treatment not necessary, thereby representing a waste of resources? Was it necessary and failure to continue meant a greater risk of events? M

16 Percent Increase in Hospitalization Rates in Patients Discontinuing Treatment after 1st Presciption (vs non-drug users, 23-28) Antihypertensive drugs Lipid lowering drugs Antidiabetic drugs % 2.5% % % M Corrao, Zambon, Parodi, Merlino, Mancia, Am J Hypertens 212; 25:

17 Which factors are involved in (low) adherence to antihypertensive / lipid lowering / antidiabetic treatment in Lombardy? 1723 M

18 Discontinuation of Antihypertensive Drug Treatment (> 3 Months over 1 Year Uncovered by Prescription) according to Gender / Age Gender Age (years) Relative risk (%) F (ref) M 4-5 (ref) * At index prescription Vertical bar refers to 95% CI; adjusted for cotreatment / comorbidity / age or gender 1732 M

19 Discontinuation of Antihypertensive Therapy according to Income in Milan Residents (n = 71469, age 4-8 years) % year discontinuation Monthly HR income (95% CI) (euro) > 2333 Adjusted risk of discontinuation Adjusted risk (.98-1.) (.98-1.) ( ) ( ) > Monthly income (euro) M Corrao, Zambon, Parodi, Mezzanica, Merlino, Cesana, Mancia, J Human Hypert 29; 23:

20 Discontinuation of Antihypertensive Drug Treatment (> 3 Months over 1 Year Uncovered by Prescription) according to Cotreatments* / Comorbidities* 5 4 Antidiabetics Cotreatments Lipidlowering Antiagents depressants Comorbidities CV Renal COPD Rheumat. Dis. Cancer Dementia Relative risk (%) * Up to 3 years before index prescription ; Vertical bar refers to 95% CI; adjusted for age / gender / cotreatments / comorbidity 1731 M

21 Cumulative Incidence of Discontinuation of Initial Antihypertensive Monotherapy over 1 Year in Newly Treated Hypertensives (Lombardia Data-base; n = ) Diuretics Beta-blockers Alpha-blockers Calcium channel blockers 1.83 ( ) 1.64 ( ) 1.23 ( ) 1.8 ( ) ACE-inhibitors Angiotensin-receptor blockers (.9-.94) 1226 M 28/9/212 9:7:12 24 Corrao, Zambon, Parodi, Poluzzi, Baldi, Merlino, Cesana, Mancia, J Hypert 28; 26:

22 Discontinuation Rate with Mono and Combination Therapy vs Diuretic Monotherapy (9 months data, n = 43368)* Diuretic-based Non-diuretic-based Mono D Combo with D Mono Combo % Discontinuation rate Use % * Adjusted for age / gender / use of non-hypertensive drugs; Free combinations M Corrao, Parodi, Zambon, Heiman, Filippi, Cricelli, Merlino, Mancia, J Hypertens 21; 28:

23 Effect of Initial and Subsequent BP Lowering Strategies on Coronary / Cerebrovascular Risk (n = 2965) Initial FU OR* Mono Mono Combo Combo Mono Combo Mono Combo 1. ( ).96 ( ).74 ( ) * Adjusted for age / gender / number of BP lowering drug classes during FU / concomitant use of drugs for CHF / CAD / diabetes etc M Corrao, Nicotra, Parodi, Zambon, Heiman, Merlino, Fortino, Cesana, Mancia, Hypertension 211; 58:

24 Adherence to Statin Treatment in Women and Men (n = 9832 / 22-27) Women (n = 5391) Men (n = 36931) % of patients Time covered by prescription 25% Very low 26-5% Low 51-75% Intermediate > 75% High M Corrao, Conti, Merlino, Catapano, Mancia, Clin Ther 21; 32: 3-31

25 Adherence to Statin Treatment in All Patients and in Patients with Cotreatments Lower adherence ( 5%) Higher adherence (> 5%) 7 % of patients All + Antidiabetics + Antihypertensives + Cardiac drugs (nitrates / digitalis etc) M Corrao, Conti, Merlino, Catapano, Mancia, Clin Ther 21; 32: 3-31

26 Discontinuation of Antihypertensive Drug Treatment (> 3 Months over 1 Year Uncovered by Prescription) according to Density of Municipality Population Relative risk (%) < 2.1* (ref) < < > 42.1 * Refers to inhabitants per 1 m 2 ; Vertical bar refers to 95% CI; adjusted for age / gender / cotreatments / comorbidity 173 M

27 Relative Risk of Treatment Discontinuation according to the Drug Initially Prescribed within Any Given Class ACE Inhibitors ARBS CCBs Drug Discontinuers Drug Discontinuers Drug Discontinuers Captopril Moexipril Spirapril Fosinopril Quinapril Benazepril Trandolapril Delapril Cilazapril Lisinopril Enalapril Perindopril Zofenopril Ramipril 448/ / / / / / / 64 23/ / / / / / /8153 Losartan Eprosartan Telmisartan Irbesartan Candesartan Valsartan Olmesartan 1325/ / / / / / /44212 Nicardipine Diltiazem Nisoldipine Verapamil Nifedipine Felodipine Lacidipine Amlodipine Nitrendipine Isradipine Manidipine Lercanidipine Barnidipine Gallopamil 269/ / / / / / / / / / / / / / Risk of discontinuation Risk of discontinuation Risk of discontinuation Diuretics Antisympathetic Agents Beta Blockers Drug Discontinuers Drug Discontinuers Drug Discontinuers Torusemide Spironolactone Furosemide Canrenone Potassium canrenoate Hydrochlorothiazide Chlorthalidone Indapamide Metolazone 2713/62 859/ / / / / / /48 2/ 55 Clonidine Terazosin Doxazosin Moxonidine Methyldopa 774/ / / /1326 9/ 91 Pindolol Propranolol Carvedilol Sotalol Bisoprolol Metoprolol Timolol Acebutolol Atenolol Labetalol Nebivolol Betaxolol Celiprolol 5/ / / / / / / 87 31/ / / / / 79 3/ Risk of discontinuation Risk of discontinuation Risk of discontinuation M Mancia, et al J Hypert 211,29,

28 Discontinuation of Initial Monotherapy within Antihypertensive Drug Classes Drug Captopril Moexipril Spirapril Fosinopril Quinapril Benazepril Trandolapril Delapril Cilazapril Lisinopril Enalapril Perindopril Zofenopril Ramipril M ACE inhibitors Standardized discontinuation rate (1 patients/month) Drug Losartan Eprosartan Telmisartan Irbesartan Candesartan Valsartan Olmesartan Angiotensin receptor antagonists Standardized discontinuation rate (1 patients/month) Mancia et al., J Hypert 211; 29:

29 Adherence to Treatment with Different Statins in Lombardy (22-27) Time covered by prescription 25% > 75% % of patients Statin Atorva Fluva Prava Simva Atorva Fluva Prava Simva M Corrao, Conti, Merlino, Catapano, Mancia, Clin Therap 21; 32: 3

30 Discontinuation of Treatment - Factors Involved Less in males Large between drugs Less with concomitant antidiabetic drugs Less with comorbidities More in densely populated areas Antihypertensives Yes Yes Yes Yes Yes Lipid lowering drugs Yes No Yes Yes Yes 1768 M

31 Take-home Message Discontinuation of antihypertensive, lipid lowering and antidiabetic treatment is extremely frequent in real life, and has a close relationship with the risk of hospitalization Analysis of administrative data-bases represent a powerful tool to investigate this problem and its evolution with time 1756 M