A Review of Perindopril in the Reduction of Cardiovascular Events

Figures & data

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 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.

Baseline clinical characteristics	Perindopril (n=6110)	Placebo (n=6108)
Age, years (SD)	60 (9)	60 (9)
Female sex	14.5%	14.7%
History of CHD
MI	64.9%	64.7%
PCI	29.0%	29.5%
CABG	29.3%	29.4%
Documented CHD
Angiographic evidence*	60.4%	60.5%
Positive stress test†	22.6%	23.3%
Previous stroke or TIA	3.4%	3.3%
Peripheral vascular disease	7.1%	7.4%
Hypertension‡	27.0%	27.2%
Diabetes mellitus	11.8%	12.8%
Hypercholesterolemia§	63.3%	63.3%
Medication
Platelet inhibitors	91.9%	92.7%
Lipid-lowering therapy	57.8%	57.3%
β blockers	62.0%	61.3%
Calcium-channel blockers	31.7%	31.0%
Nitrates	42.8%	43.0%
Diuretics	9.1%	9.4%
SBP (SD)	137 (16)	137 (15)

* 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 artery bypass graft; CHD, coronary heart disease; DBP, diastolic blood pressure; ECG, electrocardiograph; PCI, percutaneous coronary intervention, MI, myocardial infarction; SBP, systolic blood pressure; SD, standard deviation; TIA, transient ischemic attack.

Table 2 Summary of PROGRESS trial

Inclusion criteria: Men and women, aged >18 years, with history of stroke or TIA within the previous 5 years. Individuals with hypertension treated with agents other than ACEI.

Exclusion criteria: Definite indication for treatment with ACEI (such as heart failure); definite contraindication to treatment with ACEI (such as previous intolerance).

Primary outcome: total stroke (fatal and non-fatal).

Secondary outcomes: fatal or disabling stroke; total major vascular events comprising the composite of non-fatal stroke, non-fatal MI, or death due to any vascular cause (including unexplained sudden death); total and cause-specific deaths; and hospital admissions. Other outcomes analyzed included major coronary events (defined as non-fatal MI or death ascribed to CHD); total coronary events (non-fatal MI, death ascribed to CHD, coronary revascularization (PCI, CABG), or hospitalization due to unstable angina; congestive heart failure resulting in death, hospitalization, or requiring withdrawal of randomized therapy. Two subgroup analyses were prespecified: separate estimates of treatment effects for combination (perindopril and indapamide) therapy and single (perindopril alone) therapy; and separate estimates of treatment effects for participants classified as hypertensive (SBP >160 mm Hg or DBP >90 mm Hg) and those classified as nonhypertensive at enrollment.

Data derived from PROGRESS 2001, ^Citation2003.

Baseline clinical characteristics	Perindopril (n=3051)	Placebo (n=3054)
Age, years (SD)	64 (10)	64 (10)
Female sex	30%	30%
Asian*	39%	39%
Cerebro-vascular disease history
Ischemic stroke	71%	71%
Cerebral hemorrhage	11%	11%
Unknown stroke	4%	5%
TIA or amaurosis fugax	22%	22%
CHD†	16%	16%
Peripheral vascular disease	4%	4%
Hypertension‡	48%	48%
Atrial fibrillation	8%	8%
LVH on ECG	7%	7%
Diabetes mellitus	13%	12%
Current smoker	20%	20%
Medication
Platelet inhibitors	73%	72%
Statins	8%	8%
β blockers	17%	18%
Calcium-channel blockers	40%	40%
Diuretics	11%	12%
Other antihypertensives	11%	12%
Oral anticoagulants	9%	10%
SBP (SD)	147 (19)	147 (19)

* Asian: participants recruited from People's Republic of China or Japan;

† history of MI or coronary revascularization, or angina (supported by documented ECG or angiographic evidence of coronary disease);

‡ Hypertension: SBP ≥160mm Hg or DBP ≥90 mm Hg.

Abbreviations: ACEI, angiotensin converting enzyme inhibitor; CABG, coronary artery bypass graft; CHD, coronary heart disease; DBP, diastolic blood pressure; ECG, electrocardiograph; LVH, left ventricular hypertrophy; PCI, percutaneous coronary intervention, MI, myocardial infarction; SBP, systolic blood pressure; SD, standard deviation; TIA, transient ischemic attack.

Table 3 Summary of ASCOT-BLPA trial

Inclusion criteria: Men and women, aged 40–70 years, with either untreated hypertension (SBP ≥160 mm Hg, DBP ≥100 mm Hg, or both) or treated hypertension with SBP ≥140 mm Hg or DBP ≥90 mm Hg or both. In addition, subjects had to have at least three of the following cardiovascular risk factors: LVH, specified abnormalities on ECG, type 2 diabetes, peripheral arterial disease, previous stroke or TIA, male sex, age ≥55 years, microalbuminuria or proteinuria, smoking, ratio of total/HDL cholesterol ≥6, or family history of premature CHD.

Exclusion criteria: Previous MI, currently treated angina, a cerebro-vascular event within the previous 3 months, fasting triglycerides >4.5 mmol/L, heart failure, uncontrolled arrhythmias, or clinically important hematological or biochemical abnormality.

Primary outcome: composite of non-fatal MI (including silent MI) and fatal CHD.

Secondary outcomes: all-cause mortality, total stroke, primary outcome minus silent MI, all coronary events, total cardiovascular events and procedures, cardiovascular mortality, and non-fatal and fatal heart failure.

Data derived from Dahlof et al 2005.

Baseline clinical characteristics	Amlodipine/Perindopril (n=9639)	Atenolol/Bendroflumethiazide (n=9618)
Age, years (SD)	63 (9)	63 (9)
Female sex	23%	23%
Previous stroke or TIA	11%	11%
Peripheral vascular disease	6%	6%
Diabetes mellitus	27%	27%
LVH	22%	22%
Atrial fibrillation	1%	1%
ECG abnormality other than LVH	23%	23%
Other relevant cardiovascular disease	6%	5%
Current smoker	33%	32%
Total cholesterol, mmol/L (SD)	5.9 (1.1)	5.9 (1.1)
LDL cholesterol, mmol/L (SD)	3.8 (1.0)	3.8 (1.0)
HDL cholesterol, mmol/L (SD)	1.3 (0.4)	1.3 (0.4)
Triglycerides mmol/L (SD)	1.8 (1.0)	1.9 (1.0)
Medication
Previous antihypertensive medications
None	19%	19%
1	44%	45%
≥2	36%	36%
Lipid-lowering therapy	11%	10%
Aspirin use	19%	19%
SBP, mm Hg (SD)	164 (18)	164 (18)

Abbreviations: CHD, coronary heart disease; DBP, diastolic blood pressure; ECG, electrocardiograph; HDL, high density lipoprotein; LDL, low density lipoprotein; LVH, left ventricular hypertrophy; PCI, percutaneous coronary intervention, MI, myocardial infarction; SBP, systolic blood pressure; SD, standard deviation; TIA, transient ischemic attack.

Figure 1 Possible relationship between heart and blood vessel abnormalities that influence cardiac output (CO) and systemic vascular resistance (SVR), thereby influencing blood pressure (BP), and heart and blood vessel diseases that cause cardiovascular events.

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