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However, clinical diagnosis is not recorded in the database. The prescription database has been used widely for research purposes in Ireland. The Irish HSE-PCRS database was used to identify patients 16 years old and over prescribed any medications between 1 January 2000 and 30 April 2009 (n= 2?192?227). From the study population, patients co-prescribed ACEIs (ATC = C09A, C09B) and ARBs (ATC = http://www.selleckchem.com/products/GDC-0449.html C09C, C09D) in the same prescription claim form were identified (n= 18?337, 266?554 prescriptions). In addition, the presence of hypertension, diabetes, heart failure and IHD were identified using prescriptions as surrogate markers for the diseases. Patients with three or more prescriptions of (i) major classes of anti-hypertensive agents besides ACEIs and ARBs: ��-adrenoceptor blockers (ATC = C07), diuretics (ATC = C03A, C03B), or calcium https://en.wikipedia.org/wiki/Quinapyramine channel blockers (ATC = C08) as markers of hypertension (n= 467?582), (ii) insulin (ATC = A10A) or oral hypoglycaemic agents (ATC = A10B) as markers for diabetes mellitus (n= 101?263), (iii) high ceiling loop diuretics (ATC = C03C) as markers of heart failure (n= 207?658) and (iv) nitrate (ATC = C01DA) or nicorandil (ATC = C01DX16) with aspirin (ATC = B01AC06, N02BA01) as markers of IHD (n= 84?364) were identified to examine the trends in co-prescribing of ACEIs and ARBs in these cohorts. The rate of co-prescribing of ACEIs and ARBs per 1000 GMS eligible population http://www.selleckchem.com/products/MS-275.html was calculated for each month from January 2000 to April 2009 (112 months) and according to gender and age groups (defined as 16�C44, 45�C64 and ��65 years old). The co-prescribing rates in cohorts with hypertension, diabetes, heart failure and IHD were also calculated. A test for linear trend using regression analysis was used to examine the trends in co-prescribing of ACEIs and ARBs over the study period. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) of ACEI and ARB co-prescribing in females compared with males and in age groups 45�C64 years and 65 years and above compared with those below 45 years old. The OR with 95% CIs adjusted for age and gender in those with diabetes, heart failure, hypertension or IHD were calculated compared with the general GMS population without these conditions. The effects of the four major clinical trials on the co-prescription of ACEIs and ARBs was examined using segmented regression analysis [14]. The 12-month period before and after the respective clinical trials was used for this purpose; January 2000 to December 2001 for the CALM trial [5], January 2002 to December 2003 for the COOPERATE trial [7], December 2002 to November 2004 for the VALIANT trial [9] and May 2007 to April 2009 for the ONTARGET trial [6]. Analysis was performed using SAS version 9.1 (SAS institute Inc., Cary, USA). Significance at P