Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of reninangiotensinaldosterone system inhibitors involving 158 998 patients

AimsRenin-Angiotensin-Aldosterone system (RAAS) inhibitors are well established for the reduction in cardiovascular morbidity, but their impact on all-cause mortality in hypertensive patients is uncertain. Our objective was to analyse the effects of RAAS inhibitors as a class of drugs, as well as of angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) separately, on all-cause mortality. Methods and resultsWe performed a pooled analysis of 20 cardiovascular morbiditymortality trials. In each trial at least two-thirds of the patients had to be diagnosed with hypertension, according to the trial-specific definition, and randomized to treatment with an RAAS inhibitor or control treatment. The cohort included 158 998 patients (71 401 RAAS inhibitor; 87 597 control). The incidence of all-cause death was 20.9 and 23.3 per 1000 patient-years in patients randomized to RAAS inhibition and controls, respectively. Overall, RAAS inhibition was associated with a 5 reduction in all-cause mortality (HR: 0.95, 95 CI: 0.911.00, P = 0.032), and a 7 reduction in cardiovascular mortality (HR: 0.93, 95 CI: 0.880.99, P = 0.018). The observed treatment effect resulted entirely from the class of ACE inhibitors, which were associated with a significant 10 reduction in all-cause mortality (HR: 0.90, 95 CI: 0.840.97, P = 0.004), whereas no mortality reduction could be demonstrated with ARB treatment (HR: 0.99, 95 CI: 0.941.04, P = 0.683). This difference in treatment effect between ACE inhibitors and ARBs on all-cause mortality was statistically significant (P-value for heterogeneity 0.036). ConclusionIn patients with hypertension, treatment with an ACE inhibitor results in a significant further reduction in all-cause mortality. Because of the high prevalence of hypertension, the widespread use of ACE inhibitors may result in an important gain in lives saved

The effect of transcatheter aortic valve implantation on pulmonary artery pressures in a patient suffering from chronic heart failure:A case report

BACKGROUND: Pulmonary hypertension (PH) is most commonly caused by left-sided heart disease and may negatively affect the long-term prognosis and quality of life of patients with chronic heart failure (CHF). CardioMEMS (Micro-Electro-Mechanical-System) allows physicians to monitor pulmonary artery (PA) pressures remotely and optimize heart failure treatment based on haemodynamic parameters, which provides further insight into the effect of valvular interventions. CASE SUMMARY: We present a case of a 61-year-old male patient with an ischaemic cardiomyopathy, poor LV function, moderate to severe mitral regurgitation, and severe aortic valve regurgitation in refractory heart failure. Right heart catheterization and CardioMEMS monitoring revealed severe pulmonary hypertension with mean PA pressures of 55 mmHg and a mean pulmonary capillary wedge pressure of 21 mmHg despite up titration of heart failure medication and sildenafil. Pulmonary and systemic causes of pulmonary hypertension were excluded. After heart team consensus, the patient underwent transcatheter aortic valve implantation (TAVI) which resulted in normalization of PA pressures and a significant improvement of functional performance. DISCUSSION: To the best of our knowledge, this is the first case report describing the direct effects of TAVI on continuous PA pressures in a patient with poor LV function and severe aortic regurgitation. Elective TAVI appeared to be safe and very effective in reverting severe pulmonary hypertension. Most strikingly, drug interventions could not affect the elevated pulmonary pressures, but TAVI corrected the aortic valve insufficiency with normalization of left-sided pulmonary hypertension

Individualised therapy of angiotensin converting enzyme (ACE) inhibitors in stable coronary artery disease: overview of the primary results of the PERindopril GENEtic association (PERGENE) study

In patients with stable coronary artery disease (CAD) without overt heart failure, ACE inhibitors are among the most commonly used drugs as these agents have been proven effective in reducing the risk of cardiovascular events. Considerable individual variations in the blood pressure response to ACE inhibitors are observed and as such heterogeneity in clinical treatment effect would be likely as well. Assessing the consistency of treatment benefit is essential for the rational and cost-effective prescription of ACE inhibitors. Information on heterogeneities in treatment effect between subgroups of patients could be used to develop an evidence-based guidance for the installation of ACE-inhibitor therapy. Obviously, therapy should only be applied in those patients who most likely will benefit. Attempts to develop such treatment guidance by using clinical characteristics have been unsuccessful. No heterogeneity in risk reduction by ACE inhibitors has been observed in relation to relevant clinical characteristics. A new approach to such ‘guided-therapy’ could be to integrate more patient-specific characteristics such as the patients’ genetic information. If proven feasible, pharmacogenetic profiling could optimise patients’ benefit of treatment and reduce unnecessary treatment of patients. Cardiovascular pharmacogenetic research of ACE inhibitors in coronary artery disease patients is in a formative stage and studies are limited. The PERGENE study is a large pharmacogenetic substudy of the EUROPA trial, aimed to assess the achievability of pharmacogenetic profiling. We provide an overview of the main results of the PERGENE study in terms of the genetic determinants of treatment benefit and blood pressure response. The main results of the PERGENE study show a pharmacogenetic profile related to the treatment benefit of perindopril identifying responders and non-responders to treatment

The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials

Objectives To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus