The Treatment Effect of an ACE-Inhibitor Based Regimen with Perindopril in Relation to Beta-Blocker use in 29,463 Patients with Vascular Disease: a Combined Analysis of Individual Data of ADVANCE, EUROPA and PROGRESS Trials

Abstract

IntroductionIn everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking.MethodsIn this retrospective pooled analysis of three large perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke.ResultsThe cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71–0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65–0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68–0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75–1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use.ConclusionsThese data suggest that the beneficial cardioprotective effects of perindopril treatment are additive to the background beta-blockers use.

The Connotation of Variances in the Risk Predictors, Medications, Homocysteine, and Homocysteine Pathway Gene Polymorphisms with CVA/Stroke

“… 10 19 27 The use of β antagonists, calcium channel antagonists, and ACE inhibitors/ARI carry disparate results, with some studies displaying benefit and others no benefit (or high risk) in stroke prevention or adverse outcomes. 16 17 28 29 30 31 The diuretics are the mainstay of treatment in heart failure and are used as prophylaxis management regimen for stroke. An added list of literature cites use of diuretics in hypertensive patients and favorable outcomes regarding cardiac and cerebral events.…”

“…The use of angiotensin converting enzyme (ACE) inhibitors and β blockers either alone or in combination gives dissimilar results in end point occurrence of stroke and/or fatal outcomes. 16 17 Stroke in hypertensive patients developed despite using the forementioned antihypertensive medications, possible due to less optimal dosage or compliance to therapy. 18 Statin usage and low dose aspirin administration (more advantage in combination therapy) is additionally associated with lower risk of cerebral vascular disease outcomes.…”

Terapia szyta na miarę czyli jak poprawić skuteczność leczenia i rokowanie chorego. Intensyfikacja leczenia hipotensyjnego krok po kroku — od monoterapii do leków złożonych

“…pacjentów, wykazano istotne zmniejszenie ryzyka zdarzeń CV u chorych leczonych połączeniem perindoprilu z beta--adrenolitykiem w porównaniu z leczeniem samym beta--adrenolitykiem [32].…”

Fatal outcome of late-onset angiotensin-converting enzyme inhibitor induced angioedema

“…[ 1 ] For instance, ACE inhibitors are prescribed in 65% of patients with coronary artery disease and in 71% of patients with heart failure. [ 2 ] Although ACE inhibitors are well established, medication side effects may present. From 0.1% to 0.7% of patients using ACE inhibitors can develop life-threatening adverse effect, angioedema, which is characterized as nonallergic, because it is not associated with degranulation of mast cells by immunoglobulin-E. [ 3 ] Angioedema can present in different body locations, for example, face, lips, tongue, throat, and viscera.…”