However, it does provide limited evidence for the effect of perindopril in combination with amlodipine on cardiovascular events

However, it does provide limited evidence for the effect of perindopril in combination with amlodipine on cardiovascular events. greater reduction in cardiovascular events was associated with greater reduction of blood pressure. Perindopril may need to be combined with other antihypertensive brokers to maximize reduction of cardiovascular events. strong class=”kwd-title” Keywords: Angiotensin-converting enzyme inhibitor, hypertension, coronary heart disease, stroke, myocardial infarction, heart failure Introduction Angiotensin-converting enzyme inhibitors (ACEI) have a well established role in prevention of cardiovascular events in hypertension (Chobanian et al 2003; BPLTTC 2005), left ventricular dysfunction (Flather et al 2000), and heart failure (Flather et al 2000; Remme and Swedberg 2001; Hunt et al 2005). More recently, ACEI have been shown to prevent cardiovascular events in individuals with increased cardiovascular risk, where hypertension, left ventricular dysfunction, or heart failure was not the primary indication for ACEI therapy (HOPE 2000; PROGRESS 2001, 2003; EUROPA 2003). This review will summarise and comment on three recent studies of the effects of the ACEI perindopril on cardiovascular events, the EUROPA (European Trial on Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery Disease Study) and PROGRESS (Perindopril Protection Against Recurrent Stroke Study) studies where the effects of perindopril were studied alone (PROGRESS 2001, 2003; EUROPA 2003), or in combination with the diuretic indapamide (PROGRESS 2001, 2003), and the ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial C Blood Pressure Lowering Arm) study where perindopril was added to therapy with the calcium-channel blocker amlodipine (Dahlof et al 2005). ASCOT-BPLA provides no direct evidence about the effects of perindopril on cardiovascular events (Dahlof et al 2005). However, it does provide limited evidence for the effect PTPSTEP of perindopril in combination with amlodipine on cardiovascular events. The vast majority of subjects allocated to amlodipine-based therapy in ASCOT-BPLA required one or more additional antihypertensive brokers which, for 59% of subjects, included perindopril. Thus, perindopril played an essential role in blood pressure (BP) reduction for most subjects allocated to the amlodipine-based regimen. EUROPA EUROPA was a randomized placebo-controlled, double-blind study of the effects of perindopril therapy on cardiovascular events in 12 218 subjects with previous myocardial infarction (MI), angiographic evidence of coronary heart disease (CHD), coronary revascularization, or a positive stress test GDC-0927 Racemate (Table 1) (EUROPA 2003). Past history of heart failure was recorded in 1.3% of subjects, but none had clinical signs of heart failure, with 10% in New York Heart Association class I and none in class II or higher. Subjects were randomized to either 8 mg perindopril or placebo. Table 1 Summary of EUROPA trial Inclusion criteria: Men and women, aged 18 years, with CHD (previous MI, PCI, CABG, or angiographic evidence*), and without clinical evidence of heart failure. Men were also recruited if they had a history of chest pain and a positive ECG, echocardiograph, or nuclear stress test.Exclusion criteria: Clinical evidence of heart failure, planned revascularization, hypotension (SBP 110 mm Hg), uncontrolled hypertension (SBP 180 mm Hg, DBP 100 mm Hg, or both), recent use of ACEI or ARB, creatinine 0.15 mmol/L, serum potassium 5.5 mmol/L.Primary outcome: composite of cardiovascular death, non-fatal MI, and GDC-0927 Racemate cardiac arrest with successful resuscitation.Secondary outcomes: composite of total mortality, non-fatal MI, hospital admission for unstable angina, and cardiac arrest with successful resuscitation; cardiovascular mortality and non-fatal MI, as well as individual components of these secondary outcomes and revascularization, stroke, and admission for heart failure.Data derived from EUROPA 2003. Open in a separate GDC-0927 Racemate windows thead th align=”left” rowspan=”1″ colspan=”1″ Baseline clinical characteristics /th th align=”left” rowspan=”1″ colspan=”1″ Perindopril (n=6110) /th th align=”left” rowspan=”1″ colspan=”1″ Placebo (n=6108) /th /thead Age, years (SD)60 (9)60 (9)Female sex14.5%14.7%History of CHD?MI64.9%64.7%?PCI29.0%29.5%?CABG29.3%29.4%Documented CHD?Angiographic evidence*60.4%60.5%?Positive stress test?22.6%23.3%Previous stroke or TIA3.4%3.3%Peripheral vascular disease7.1%7.4%Hypertension?27.0%27.2%Diabetes mellitus11.8%12.8%Hypercholesterolemia63.3%63.3%Medication?Platelet inhibitors91.9%92.7%?Lipid-lowering therapy57.8%57.3%? blockers62.0%61.3%?Calcium-channel blockers31.7%31.0%?Nitrates42.8%43.0%?Diuretics9.1%9.4%SBP (SD)137 (16)137 (15) Open in a separate window *Angiographic evidence of CHD: stenosis 70%. ?Positive stress test: only in men. ?Hypertension: BP 160/95mm Hg or receiving antihypertensive treatment. Hypercholesterolemia: cholesterol 6.5 mmol/L or receiving lipidlowering treatment. Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin type 1 receptor blocker; CABG, coronary.