Choice of antihypertensive drug in the diabetic patient

The hypertensive patient with type 2 diabetes is especially at risk of adverse cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) studies suggested that treatment to a lower target blood pressure resulted in better prevention of clinical disease in these patients. Most trials comparing antihypertensive drugs have shown only minimal differences between the various agents. The evidence from the trials suggests that diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and the angiotensin-receptor antagonists (ARBs) will all successfully reduce adverse clinical events. The largest of the comparative hypertensive drug trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrated that a diuretic has a better hypotensive effect, and was more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors. The importance of good blood pressure control and the general equivalence of antihypertensive drugs were again shown in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which compared an ARB with a CCB. Choice of antihypertensive agent should be individualized and guided by the presence of concomitant clinical disease and the need to protect any specific target organ system in the diabetic hypertensive. Diuretics, being potent hypotensive drugs with clearly demonstrated clinical benefit, should form part of the antihypertensive regimen of most diabetic hypertensives. ACE inhibitors and ARBs are especially useful in preventing nephropathy. Most patients will require a combination of antihypertensive drugs to achieve tight blood pressure control of under 130/80 mm Hg in the diabetic hypertensive. The clinician should concentrate on seeking this lower target blood pressure rather than be excessively concerned about which is the best antihypertensive agent.     

Evidence of suboptimal management of cardiovascular risk in patients with type 2 diabetes mellitus and symptomatic atherosclerosis

Background

Given that most deaths among patients with diabetes mellitus are due to cardiovascular disease, we sought to determine the extent to which medications proven to reduce cardiovascular mortality are prescribed for patients with type 2 diabetes who have symptomatic atherosclerosis (i.e., coronary artery disease [CAD], cerebrovascular disease [CBVD] or peripheral arterial disease [PAD]).

Methods

Administrative records from Saskatchewan Health were used to evaluate the use of antiplatelet agents, statins and angiotensin-converting enzyme (ACE) inhibitors by people with treated type 2 diabetes with and without symptomatic atherosclerosis. CAD and CBVD were defined by International Classification of Diseases (ninth revision) codes, and PAD was defined on the basis of pentoxifylline use or lower limb amputation. Multivariate logistic regression analysis was used to compare medication use in patients with and without PAD, with adjustments for differences in age, sex and comorbidity.

Results

In this cohort of 12 106 patients with type 2 diabetes (mean age 64 years, 55% male, mean follow-up 5 years), fewer than 25% received an antiplatelet agent or statin, and fewer than 50% received an ACE inhibitor. Although patients with CAD were more likely to receive antiplatelet agents, statins or ACE inhibitors than people without CAD (p < 0.001 for all), the overall use of these medications was suboptimal (37%, 29% and 60% respectively among patients with symptomatic CAD). Similar patterns of practice were found for patients with symptomatic CBVD and PAD. All 3 proven efficacious therapies were prescribed for only 11% of patients with CAD, 22% with CBVD and 12% with PAD. Patients with PAD who had undergone lower limb amputation were no more likely to subsequently receive antiplatelet agents or statins than those without an amputation.

Interpretation

Diabetic patients with symptomatic atherosclerotic disease are undertreated with medications known to reduce cardiovascular morbidity and mortality, perhaps because of a “glucocentric” view of diabetes. Programs to improve the quality of cardiovascular risk reduction in these high-risk patients are needed.Diabetes mellitus in adults is associated with an annual rate of death of about 5%, approximately double the rate for age- and sex-matched control subjects without diabetes. Most of this excess mortality risk is attributable to macrovascular atherosclerotic disease.¹ Thus, it has been recommended that medical management to decrease cardiovascular risk should start when type 2 diabetes mellitus is diagnosed.^2,3 At the very least, medications proven to reduce cardiovascular risk should be prescribed for patients with diabetes and established atherosclerotic disease.In addition to smoking cessation and control of blood pressure, strategies proven to reduce cardiovascular risk in patients with diabetes and established atherosclerotic disease include therapy with antiplatelet agents, statins and angiotensin-converting enzyme (ACE) inhibitors.² Coronary artery disease (CAD), cerebrovascular disease (CBVD) and peripheral arterial disease (PAD) are all manifestations of established atherosclerosis.⁴ Recent epidemiologic studies have suggested that PAD may be present in one-quarter to one-half of all adults with type 2 diabetes and have confirmed that PAD is a powerful predictor of cardiovascular death.⁴ In fact, the survival rate for patients with PAD is worse than that for patients with breast cancer (72% v. 85% at 5 years).⁴ However, a recently published survey suggested that clinicians were less likely to prescribe antiplatelet therapy for patients with PAD than for patients with CAD.⁵We sought to evaluate the use of antiplatelet agents, statins and ACE inhibitors among diabetic patients with and without symptomatic atherosclerotic vascular disease. Given the high prevalence of symptomatic PAD among diabetic patients and suggestions that it is often neglected as a marker of atherosclerotic disease, we were particularly interested in examining patterns of care for overall cardiovascular risk reduction in patients with this condition.⁴     

Stroke: development, prevention and treatment with peptidase inhibitors

Stroke is the leading cause of long-term disability in the United States and affects more people than any other neurologic disorder. Hypertension is a major risk factor associated with stroke. Several anti-hypertensive agents have been used to treat chronic hypertension to reduce the morbidity and mortality of stroke. Previous experimental studies have shown reduced stroke mortality with angiotensin-converting enzyme (ACE) inhibitors. This review discusses the development of stroke and potential use of ACE inhibitors in prevention and treatment of this disease. Furthermore, this review focuses on current investigations aimed at cellular mechanisms involved in stroke-induced microvascular alterations.     

Stroke: development, prevention and treatment with peptidase inhibitors

Stroke is the leading cause of long-term disability in the United States and affects more people than any other neurologic disorder. Hypertension is a major risk factor associated with stroke. Several anti-hypertensive agents have been used to treat chronic hypertension to reduce the morbidity and mortality of stroke. Previous experimental studies have shown reduced stroke mortality with angiotensin-converting enzyme (ACE) inhibitors. This review discusses the development of stroke and potential use of ACE inhibitors in prevention and treatment of this disease. Furthermore, this review focuses on current investigations aimed at cellular mechanisms involved in stroke-induced microvascular alterations.     

ACE inhibition and atherogenesis

Recent clinical studies such as HOPE, SECURE, and APRES show that angiotensin-converting enzyme (ACE) inhibitors like ramipril improve the prognosis of patients with a high risk of atherothrombotic cardiovascular events. Atherosclerosis, as a chronic inflammatory condition of the vascular system, can turn into an acute clinical event through the rupture of a vulnerable atherosclerotic plaque followed by thrombosis. ACE inhibition has a beneficial effect on the atherogenic setting and on fibrinolysis. Endothelial dysfunction is the end of a common process in which cardiovascular risk factors contribute to inflammation and atherogenesis. By inhibiting the formation of angiotensin II, ACE inhibitors prevent any damaging effects on endothelial function, vascular smooth muscle cells, and inflammatory vascular processes. An increase in the release of NO under ACE inhibition has a protective effect. Local renin-angiotensin systems in the tissue are involved in the inflammatory processes in the atherosclerotic plaque. Circulating ACE-containing monocytes, which adhere to endothelial cell lesions, differentiate within the vascular wall to ACE-containing macrophages or foam cells with increased local synthesis of ACE and angiotensin II. Within the vascular wall, angiotensin II decisively contributes to the instability of the plaque by stimulating growth factors, adhesion molecules, chemotactic proteins, cytokines, oxidized LDL, and matrix metalloproteinases. Suppression of the increased ACE activity within the plaque can lead to the stabilization and deactivation of the plaque by reducing inflammation in the vascular wall, thus lessening the risk of rupture and thrombosis and the resultant acute clinical cardiovascular events. The remarkable improvement in the long-term prognosis of atherosclerotic patients with increased cardiovascular risk might be the clinical result of the contribution made by ACE inhibition in the vascular wall.     

ACE2: A novel therapeutic target for cardiovascular diseases

Hypertension afflicts over 65 million Americans and poses an increased risk for cardiovascular morbidity such as stroke, myocardial infarction and end-stage renal disease resulting in significant mortality. Overactivity of the renin-angiotensin system (RAS) has been identified as an important determinant that is implicated in the etiology of these diseases and therefore represents a major target for therapy. In spite of the successes of drugs inhibiting various elements of the RAS, the incidence of hypertension and cardiovascular diseases remain steadily on the rise. This has lead many investigators to seek novel and innovative approaches, taking advantage of new pathways and technologies, for the control and possibly the cure of hypertension and related pathologies. The main objective of this review is to forward the concept that gene therapy and the genetic targeting of the RAS is the future avenue for the successful control and treatment of hypertension and cardiovascular diseases. We will present argument that genetic targeting of angiotensin-converting enzyme 2 (ACE2), a newly discovered member of the RAS, is ideally poised for this purpose. This will be accomplished by discussion of the following: (i) summary of our current understanding of the RAS with a focus on the systemic versus tissue counterparts as they relate to hypertension and other cardiovascular pathologies; (ii) the newly discovered ACE2 enzyme with its physiological and pathophysiological implications; (iii) summary of the current antihypertensive pharmacotherapy and its limitations; (iv) the discovery and design of ACE inhibitors; (v) the emerging concepts for ACE2 drug design; (vi) the current status of genetic targeting of the RAS; (vii) the potential of ACE2 as a therapeutic target for hypertension and cardiovascular disease treatment; and (viii) future perspectives for the treatment of cardiovascular diseases.     

Cardiovascular and Renal Outcomes of Renin–Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses

Background

Medications aimed at inhibiting the renin–angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes.

Methods and Findings

Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke—singly and as a composite endpoint, major cardiovascular outcome—and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality—singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90–1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79–1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96–1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73–1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90–1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72–1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65–1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78–1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies. Potential inconsistency was identified in network meta-analyses of stroke and angina pectoris, limiting the conclusiveness of findings for these single endpoints.

Conclusions

In adults with diabetes, comparisons of different RAS blockers showed similar effects of ACE inhibitors and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies, the combination of an ACE inhibitor and an ARB failed to provide significant benefits on major outcomes. Clinicians should discuss the balance between benefits, costs, and potential harms with individual diabetes patients before starting treatment.

Review registration

PROSPERO CRD42014014404     

Novel peptide inhibitors of angiotensin-converting enzyme 2

Angiotensin-converting enzyme 2 (ACE2), a recently identified human homolog of ACE, is a novel metallocarboxypeptidase with specificity, tissue distribution, and function distinct from those of ACE. ACE2 may play a unique role in the renin-angiotensin system and mediate cardiovascular and renal function. Here we report the discovery of ACE2 peptide inhibitors through selection of constrained peptide libraries displayed on phage. Six constrained peptide libraries were constructed and selected against FLAG-tagged ACE2 target. ACE2 peptide binders were identified and classified into five groups, based on their effects on ACE2 activity. Peptides from the first three classes exhibited none, weak, or moderate inhibition on ACE2. Peptides from the fourth class exhibited strong inhibition, with equilibrium inhibition constants (K(i) values) from 0.38 to 1.7 microm. Peptides from the fifth class exhibited very strong inhibition, with K(i) values < 0.14 microm. The most potent inhibitor, DX600, had a K(i) of 2.8 nm. Steady-state enzyme kinetic analysis showed that these potent ACE2 inhibitors exhibited a mixed competitive and non-competitive type of inhibition. They were not hydrolyzed by ACE2. Furthermore, they did not inhibit ACE activity, and thus were specific to ACE2. Finally, they also inhibited ACE2 activity toward its natural substrate angiotensin I, suggesting that they would be functional in vivo. As novel ACE2-specific peptide inhibitors, they should be useful in elucidation of ACE2 in vivo function, thus contributing to our better understanding of the biology of cardiovascular regulation. Our results also demonstrate that library selection by phage display technology can be a rapid and efficient way to discover potent and specific protease inhibitors.     

Novel mechanism of inhibition of human angiotensin-I-converting enzyme (ACE) by a highly specific phosphinic tripeptide

Human ACE (angiotensin-I-converting enzyme) has long been regarded as an excellent target for the treatment of hypertension and related cardiovascular diseases. Highly potent inhibitors have been developed and are extensively used in the clinic. To develop inhibitors with higher therapeutic efficacy and reduced side effects, recent efforts have been directed towards the discovery of compounds able to simultaneously block more than one zinc metallopeptidase (apart from ACE) involved in blood pressure regulation in humans, such as neprilysin and ECE-1 (endothelin-converting enzyme-1). In the present paper, we show the first structures of testis ACE [C-ACE, which is identical with the C-domain of somatic ACE and the dominant domain responsible for blood pressure regulation, at 1.97? (1 ?=0.1 nm)] and the N-domain of somatic ACE (N-ACE, at 2.15?) in complex with a highly potent and selective dual ACE/ECE-1 inhibitor. The structural determinants revealed unique features of the binding of two molecules of the dual inhibitor in the active site of C-ACE. In both structures, the first molecule is positioned in the obligatory binding site and has a bulky bicyclic P(1)' residue with the unusual R configuration which, surprisingly, is accommodated by the large S(2)' pocket. In the C-ACE complex, the isoxazole phenyl group of the second molecule makes strong pi-pi stacking interactions with the amino benzoyl group of the first molecule locking them in a 'hand-shake' conformation. These features, for the first time, highlight the unusual architecture and flexibility of the active site of C-ACE, which could be further utilized for structure-based design of new C-ACE or vasopeptidase inhibitors.     

Lack of association of ACE/angiotensinogen genotype with renal function in autosomal dominant polycystic kidney disease

ACE polymorphisms have recently been shown to associate with worse renal and or cardiovascular outcome, with the D allele widely reported as a risk factor for cardiovascular disease. In autosomal dominant polycystic kidney disease (ADPKD), there are conflicting reports of an association between ACE polymorphisms and disease phenotype. There are no previous reports of any association between angiotensinogen polymorphisms and clinical phenotype in ADPKD. We examined the ACE I/D and angiotensinogen M235T polymorphisms in 176 patients with ADPKD. Patients are categorized into three groups according to the reason for initial investigation. Clinical history and examination findings were recorded at the time of first referral. A cohort of 17 patients had progressive renal impairment observed after 3 or more years of follow-up. Reciprocal creatinine against time was plotted in this group. From the patient population of 176, a total of 33 patients reached end-stage renal failure (ESRF) or a serum creatinine greater than 500 microm/liter. ACE genotype and M235T polymorphism frequencies were compared across groups. Serum creatinine and presence of hypertension and onset of ESRF were taken as outcome variables; age and source of referral were taken as confounding variables. There was no association of any genotype or allele with either creatinine, inverse creatinine, hypertension, or age at end-stage renal failure. These findings do not support the proposition that ACE genotype or angiotensinogen polymorphisms are associated with a worse prognosis in patients with ADPKD.     

Why do antioxidants fail to provide clinical benefit?

The results of recent randomized trials to test the influence of antioxidants on coronary-event rates and prognosis in patients with coronary-artery disease were disappointing. In none of these studies did the use of vitamin E improve prognosis. In contrast, treatment of coronary-artery disease with angiotensin-converting-enzyme (ACE) inhibitors reduced coronary-event rates and improved prognosis. ACE inhibition prevents the formation of angiotensin II, which has been shown to be a potent stimulus of superoxide-producing enzymes in atherosclerosis. The findings suggest that inhibition of superoxide production at enzymatic levels, rather than symptomatic superoxide scavenging, may be the better choice of treatment.     

ACE inhibition lowers angiotensin II-induced chemokine expression by reduction of NF-kappaB activity and AT1 receptor expression

OBJECTIVE: Angiotensin converting enzyme (ACE) inhibitors significantly improve survival in patients with atherosclerosis. Although ACE inhibitors reduce local angiotensin II (AngII) formation, serine proteases form AngII to an enormous amount independently from ACE. Therefore, our study concentrates on the effect of the ACE-inhibitor ramiprilat on chemokine release, AngII receptor (ATR) expression, and NF-kappaB activity in monocytes stimulated with AngII. METHODS AND RESULTS: AngII-induced upregulation of IL-8 and MCP-1 protein and RNA in monocytes was inhibited by the AT1R-blocker losartan, but not by the AT2R-blocker PD 123.319. Ramiprilat dose-dependently suppressed AngII-induced upregulation of IL-8 and MCP-1. The suppressive effect of ramiprilat on AngII-induced chemokine production and release was in part caused by downregulation of NF-kappaB, but more by a selective and highly significant reduced expression of AT1 receptors as shown in monocytes and endothelial cells. CONCLUSION: In our study we demonstrated for the first time that ramiprilat reduced expression of AT1R in monocytes and endothelial cells. In addition, ramiprilat downregulated NF-kappaB activity and thereby reduced the AngII-induced release of IL-8 and MCP-1 in monocytes. This antiinflammatory effect, at least in part, may contribute to the clinical benefit of the ACE inhibitor in the treatment of coronary artery disease.     

Dose response of ACE inhibitors: implications of the SECURE trial

The choice of the appropriate dosage of ACE inhibitor in clinical practice is an important one. The available evidence suggests that in chronic heart failure as well as in chronic coronary artery disease, high doses of angiotensin-converting enzyme (ACE) inhibitor are more effective than low ones. The current recommended clinical approach is to target ACE inhibitor dosing regimens to be similar to those used in the clinical trials, which demonstrated mortality and morbidity benefits. When titrated appropriately, ACE inhibitors are generally well tolerated and target doses can be achieved and maintained in the majority of patients with atherosclerotic vascular disease, with or without heart failure.     

High-Resolution Crystal Structures of Drosophila melanogaster Angiotensin-Converting Enzyme in Complex with Novel Inhibitors and Antihypertensive Drugs

Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE.     

Angiotensin-converting enzyme and cardiovascular disease risk.

The published studies of the association of the angiotensin-converting enzyme (ACE) genotype with cardiovascular disease have used many different diagnostic criteria for cardiovascular disease and have drawn their samples from different patient groups and different populations. This review examines the association of the ACE DD genotype with cardiovascular disease risk in studies grouped by their case criterion, the geographical region of the population samples, and by the cardiovascular risk level of the patient sample. In studies where the underlying odds ratios are determined to be homogeneous, the overall odds ratios for myocardial infarction and coronary artery disease with regard to the ACE DD genotype are estimated using the Mantel-Haenszel method.     

Potential of Plant’s Dipeptidyl Peptidase I &amp; II Homologs in Generation of ACE Inhibitory Peptides

Synthetic inhibitors of angiotensin converting enzyme (ACE) are commonly used in the treatment of hypertension and other cardiovascular diseases. But their diverse side effects stipulated nontoxic safer and economic inhibitors which can be accomplished by using peptidyl inhibitors from natural sources or functional food ingradients. Dipeptidyl peptidases cleaved dipeptide moieties from amino terminus of oligopepides so, they may be used to generate effective dipeptidyl ACE inhibitors. In present study, role of purified DPP-I and II in generation of ACE inhibitors have been explored. Results showed that collagen alpha-1(III) from chicken showed highest ACE inhibitory potential. Both dipeptidyl peptidases hydrolysed various potent inhibitory dipeptides from their oligopeptide precursors. In addition, sequential digestion of proteins with trypsin, DPP-I and II released approximate 15 % of total inhibitory peptides. Furthermore, inhibitory peptide concentration can be increased up to 30 % or more by using more proteases in presence of DPP-I and II. Results revealed that both DPP-I and II possesses the ability to generate ACE dipeptide inhibitors from oligopeptides. Still various dipeptidyl inhibitory peptides remained in generating oligopeptides, which required study of other endopeptidases with broad specificities.     

Polymorphism of the angiotensin-converting enzyme gene in cardiovascular pathology

The aim of the study was to investigate influence of polymorphism of angiotensin-converting enzyme (ACE) gene on peculiarities of clinical process of such cardiovascular pathology as hypertrophic cardiomyopathy, coronary arterial disease and arterial hypertension. The polymorphism of ACE gene was studied in 98 patients: 38 with hypertrophic cardiomyopathy, 35 with coronary arterial disease and 25 with arterial hypertension. Nuclear DNA was extracted from blood leukocytes by phenol-chloroform method. Genotypes of ACE gene were determined by polymeraze chain reaction, followed with electrophoresis in agarose gel. It has been established, that I/D polymorphism of ACE gene has important modificative significance in clinical process at the mentioned diseases.     

The Association of Cardioprotective Medications with Pneumonia-Related Outcomes

Introduction

Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes.

Materials and Methods

We conducted a retrospective population-based study on male patients ≥65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events.

Results

Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63–0.77), ACE inhibitors (OR 0.82, 95% CI 0.74–0.91), and ARBs (OR 0.58, 95% CI 0.44–0.77). However, none of the medications were significantly associated with decreased cardiovascular events.

Discussion

While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects.