The presence of idiopathic thrombocytopenic purpura and incidence of acute non-ST elevation myocardial infarction.

Platelets play an integral role in the pathogenesis of acute coronary syndrome (ACS). The purpose of this study was to investigate any correlation between immune thrombocytopenia (ITP) and non-ST segment elevation myocardial infarction (NTSEMI), a common presentation of ACS. Using the large Nationwide Inpatient Sample (NIS) database, we studied any correlation between NSTEMI and ITP utilizing ICD-9 codes. We performed uni- and multivariate analysis adjusting for risk factors from the years 2002-2011. Data was extracted from 106,653 ITP patients and 79,636,090 controls. In multiple years of the study period (2002-2011), NSTEMI incidence was significantly higher in ITP patients when compared with non-ITP patients in the univariate analysis (odds ratio average 1.226). However, no significant association was found after adjusting for additional risk factors in multivariate analysis. Based on our large database study, ITP is not independently associated with NSTEMI incidence after adjusting for comorbidity.

Idiopathic thrombocytopenic purpura is strongly associated with higher prevalence of aortic valve disease.

Aortic valve disease (AVD) has similarities to atherosclerosis in the case of aortic stenosis. The important role of platelet in the pathogenesis of atherosclerosis is known. The goal of this study is to evaluate whether platelet disorders play any role in aortic valve disease. We used patients with idiopathic thrombocytopenic purpura (ITP) for this study. We evaluated any association between ITP and AVD using a large inpatient database. The International Classification of Diseases, Ninth Revision, and Clinical Modification (ICD-9-CM) codes for ITP and AVD from the Nationwide Inpatient Sample (NIS) database were used for this study. Uni- and multivariate analyses were performed on data from 2002 to 2011 to evaluate any association between ITP and AVD. In the 2002 database, AVD was present in 1.73% of ITP patients versus 1.12% in the control population (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.34-1.81; p < 0.001). In the 2011 database, AVD was present in 1.96% of ITP patients versus 1.33% in the control population (OR, 1.48; 95% CI, 1.30-1.68; p < 0.001). ITP remained independently associated with AVD following a multivariate logistic regression analysis adjusting for age, gender, diabetes mellitus, hypertension, and hyperlipidemia in 2002 (OR, 1.35; 95% CI, 1.16-1.57; p < 0.001) with a trend of this association in 2011 (OR, 1.12; 95% CI, 0.98-1.27; p = 0.096). ITP was strongly associated with AVD over the 10-year period analyzed in a large inpatient database. The reason for this association is not known warranting further investigations.

History of the development of antifungal azoles: A review on structures, SAR, and mechanism of action.

With the increasing risk of invasive and life threating fungal infections, there is now a great concern regarding the lower discovery rate of antifungal drugs in comparison to antimicrobial agents. Drugs conventionally used in clinics are not adequate enough to combat the increasing fungal infections, especially fungal forms resistant to fluconazole. Among the limited antifungal agents in clinics, azoles have the largest number of drug candidates in clinical trials and are partly marketed due to the particular focus of pharmaceutical companies and medicinal scientific centers. With the rise in the number of papers on azole antifungal design and discovery, a more in-depth understanding the most recent and authentic information about this class of drugs might be beneficial. To this end, we for the first time summarized the state-of-the-art information about azole drugs, with a specific focus on those in the pipelines of pharmaceutical companies, into four generations with regard to their structural similarity. More importantly, this review highlights information on the structure activity relationship (SAR), target description, hybrid antifungal agents as possible future generation, and other useful issues to streamline research towards designing new efficient azole antifungal structures in future.

State of the Art Comprehensive Review of Individual Statins, Their Differences, Pharmacology, and Clinical Implications.

Statins are currently the primary treatment for hyperlipidemia, particularly for the treatment of high levels of low-density lipoprotein cholesterol (LDL-C), as many studies have proven benefit in a variety of populations. The benefits of statin treatment for high cholesterol have been proven in many trials. Forefront among different adverse events is statin-induced myopathy, which still eludes complete understanding, and may range anywhere from muscle soreness or fatigue to potentially extremely rare occurrence of rhabdomyolysis.As most adverse events are rare and not life-threatening, in high-risk patients, a high-dose statin should be started initially as data suggests that clinicians rarely up titrate statin therapy after initial prescription leading to under-treatment of many patients requiring high-dose statin therapy. As we will discuss in this paper, musculoskeletal side effects are the main concern and reason for discontinuing statin therapy. The occurrence and true association of other adverse events in patients on statin such as new onset of diabetes, hepatic toxicity, or cognitive impairment are rare, controversial, and not proven. In placebo-controlled studies, abnormal liver function occurs to a similar degree in statin- and placebo-treated patients. This led to FDA removal of the requirement to monitor liver function tests in patients on statin therapy.The combination of statins with other compounds such as ezetimibe or PCSK9 inhibitors has shown some additional benefits in the treatment of hypercholesterolemia. The goal of this manuscript is to conduct a comprehensive review about most commonly used statins and compare data on their history, structures, benefits, adverse effects, and clinical outcomes.

A Novel Inhibitor of Protease-activated Receptor 1: A Review of Chemical Structure and Mode of Action.

Limitations of current antiplatelet therapies have led to the discovery of new antiplatelet agents with new modes of action. Vorapaxar has been developed as a thrombin receptor antagonist. This drug works against the protease-activated receptor 1 (PAR1) and inhibits platelet aggregation mediated by PAR1. This article reviews this new class of antiplatelet therapy in detail with an acute focus on the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) and TRA 2°P-TIMI 50 (Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50) trials. Vorapaxar has proven to be beneficial when administered to stable atherosclerotic patients. However, it has been shown to increase risk of intracranial hemorrhage in patients with known, previous history of cerebrovascular incidence. Despite these limitations, TRA 2°P-TIMI 50 results showed that vorapaxar appears to have a definitive therapeutic benefit when administered alongside aspirin or when it is used as an addition to dual antiplatelet therapy for patients with stable atherosclerosis.

Association Between Idiopathic Thrombocytopenic Purpura and Hemorrhagic and Nonhemorrhagic Stroke.

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is characterized by a low platelet count. This may lead to an increased risk of hemorrhagic stroke but a lower rate of nonhemorrhagic stroke. The goal of this study was to evaluate the association between ITP and both hemorrhagic and nonhemorrhagic strokes using a large database. METHODS: We used the Nationwide Inpatient Sample (NIS) database to analyze the occurrence of hemorrhagic and nonhemorrhagic stroke in patients with and without a diagnosis of ITP from 2005 to 2014. RESULTS: Univariate analysis revealed a higher incidence of hemorrhagic stroke in patients with ITP in the year studied. (for example, in 2005: OR, 1.75; 95% CI, 1.57-1.94; P < 0.001; 2014: OR, 2.19; 95% CI, 2.03-2.36; P < 0.001). After adjusting for age, gender, race, and hypertension, hemorrhagic stroke remained significantly associated with ITP (in 2005: OR, 1.85; 95% CI, 1.49-1.89; P < 0.001; 2014: OR, 2.01; 95% CI, 1.86-2.18; P < 0.001) for all the years studied. Nonhemorrhagic stroke occurred at a lower rate in patients with ITP in most years (2006: OR, 0.91; 95% CI, 0.85-0.97; P = 0.004; 2014: OR, 0.88; 95% CI, 0.83-0.93; P < 0.001). Multivariate analysis confirmed a higher rate of nonhemorrhagic stroke in ITP patients. CONCLUSION: Our analysis showed that there was a higher rate of hemorrhagic stroke but a lower rate of ischemic stroke in ITP patients, suggesting an important role of platelets in the occurrence of stroke.

Berberine: A Multi-Target Natural PCSK9 Inhibitor with the Potential to Treat Diabetes, Alzheimer's, Cancer and Cardiovascular Disease.

Berberine is a natural product with a wide range of pharmacological effects. It has antimicrobial, anti-cancer, anti-inflammatory, anti-hyperlipidemic, neuroprotective, and cholesterollowering properties, among others. It has been used in traditional Chinese and Ayurvedic medicine for 3000 years and is generally well-tolerated with few side effects. Its main drawback is low oral bioavailability, which has hindered widespread clinical use. However, recent interest has surged with the emergence of evidence that berberine is effective in treating cancer, diabetes, Alzheimer's disease, and cardiovascular disease via multiple mechanisms. It enhances insulin sensitivity and secretion by pancreatic ß-cells in Type 2 Diabetes Mellitus in addition to reducing pro-inflammatory cytokines such as IL-6, IL-1ß, TLR4 and TNF-α. These cytokines are elevated in Alzheimer's disease, cardiovascular disease, and diabetes. Reductions in pro-inflammatory cytokine levels are associated with positive outcomes such as improved cognition, reduced cardiovascular events, and improved glucose metabolism and insulin sensitivity. Berberine is a natural PCSK9 inhibitor, which contributes to its hypolipidemic effects. It also increases low-density lipoprotein receptor expression, reduces intestinal cholesterol absorption, and promotes cholesterol excretion from the liver to the bile. This translates into a notable decrease in LDL cholesterol levels. High LDL cholesterol levels are associated with increased cardiovascular disease risk. Novel synthetic berberine derivatives are currently being developed that optimize LDL reduction, bioavailability, and other pharmacokinetic properties.

Mitral annulus calcification is independently associated with all-cause mortality.

BACKGROUND: Mitral annulus calcification (MAC) is an important echocardiographic finding that is significantly associated with valvular abnormalities. However, the effect of documented MAC on all-cause mortality is not known. Using a large database, associations between MAC and long-term all-cause mortality were evaluated. METHODS: A retrospective analysis of 3169 echocardiograms, which were performed for clinical reasons in southern California between 1983 and 1998 in patients between 16 and 99 years of age, was performed. Mortality data were extracted from the national mortality database at the end of 2007. Using uni- and multivariate analysis, associations between total mortality and the echocardiographic presence of MAC documented in the final report by the interpreting cardiologist were evaluated. RESULTS: MAC was significantly associated with all-cause mortality (174 of 334 [52.1%] patients with MAC died versus 709 of 2835 [25.0%] patients without MAC; OR 3.26 [95% CI 2.58 to 4.10]; P<0.001). Using multivariate analysis adjusting for age, left ventricular hypertrophy, sex, abnormal left ventricular systolic function and significant valvular abnormalities, MAC remained independently associated with all-cause mortality (OR 2.50 [95% CI 1.81 to 3.45]; P<0.001). CONCLUSION: Using a large echocardiographic database, MAC was found to be independently associated with all-cause mortality. This finding confirms the importance of an abnormal mitral annulus as an important prognostic marker.

Higher Heart Rate Is Independently Associated With Abnormal Body Mass Index in a J Shape Pattern.

BACKGROUND: High heart rate (HR) is independently associated with higher cardiovascular mortality and usually occurs in sedentary persons. Inactivity can also lead to obesity. The purpose of this study was to evaluate the associations between body mass index as an independent marker of high HR. METHOD: Data generated from screening echocardiography, for the prevention of sudden death at the Anthony Bates Foundation, was used. Data from 1340 subjects, with documented HR and body mass index, between the ages 19-79 years with a mean age of 32 years, were studied. We correlated the presence of a high HR >90 beats per minute (bpm) with different body mass index (BMI) categories. RESULTS: High HR was significantly associated with higher BMI categories and underweight subjects in adults suggesting a J shape association. A total of 22.7% of participants with an HR of more than 90 bpm had BMI >40 kg/m 2 , versus 19.0% of patients with BMI of 35-40 kg/m 2 versus 13.5% of subjects with BMI of 30-35 kg/m 2 versus 12.2% of subjects with BMI of 25-30 kg/m 2 -29.9 kg/m 2 , versus in 10.3% of subjects with BMI between 18.5 and 25 kg/m 2 , P < 0.01) Furthermore, increased HR was also more prevalent in underweight patient (17.4% in subjects with BMI < 18.5 kg/m 2 ). CONCLUSION: High HR is strongly associated with obesity and underweight suggesting that maintaining a normal weight is associated with most positive effect on the cardiovascular system.

The Presence of Pneumonia Is Strongly Associated With Higher Prevalence of Non-ST-Elevation Myocardial Infarction Using a Large NIS Database.

OBJECTIVE: Inflammation is a risk factor for myocardial infarction. Pneumonia leads to severe inflammatory response. Some studies suggest higher risk of myocardial infarction in patients with pneumonia. We used a large inpatient database (National Inpatient Sample) to evaluate this association. METHODS: This study includes patients from a Nationwide Inpatient Sample hospital in 2005 to 2014 with International Classification of Diseases, Ninth Revision, and Clinical Modification codes consistent with pneumonia and non-ST elevation myocardial infarction (NSTEMI). Subjects were stratified into all hospitalized patients aged 30 and above. Univariate and multivariate analysis was performed adjusting for age, race, gender, tobacco use, diabetes mellitus, hypertension, and hyperlipidemia. RESULTS: NSTEMI was present in 3.2% of pneumonia patients versus 1.8% in the non-pneumonia population over 10-year period. For example, the 2005 database: [odds ratio (OR), 1.77; 95% confidence interval (CI), 1.73-1.80; P < 0.001]. For 2014, NSTEMI was present in 4.1% of pneumonia patients (PNA) versus 2.4% in the non-pneumonia population (OR, 1.72; 95% CI, 1.70-1.75; P < 0.001). NSTEMI remained independently associated with pneumonia following a multivariate analysis in 2005 (OR, 1.477; 95% CI, 1.447-1.508; P < 0.001) with a similar value in 2014 (OR, 1.445; 95% CI, 1.421-1.469; P < 0.001). CONCLUSIONS: Using a large inpatient database, we found that NSTEMI was strongly associated with PNA versus non-pneumonia population over a 10-year period. Suggesting acute inflammatory cytokines or hypoxia which occurs during lung infection may play a role in NSTEMI development, reinforcing the importance of acute cardiac monitoring in patients with PNA.

Gender based disparity in performing aortic valve surgery in the united state before availability of percutaneous valve implantation.

BACKGROUND: Aortic valve surgery has been performed increasingly in high-risk patients. The goal of this study was to evaluate this trend based on gender in the United States before the availability of percutaneous aortic valve replacement. METHOD: The Nationwide Inpatient Sample (NIS) database was utilized to calculate the age-adjusted utilization rate for aortic valve surgery from 1988 to 2011 in the United States using ICD-9 coding for aortic valve surgery. RESULTS: A total population of 258, 506 patients underwent aortic valve between 1988-2011 were available for our study over the age of 20. We found that the age-adjusted rate of aortic valve surgery gradually increased from 1988 until 2009 and stabilized thereafter with a persistently higher rate for men. For men age-adjusted rate in 1988 was 13.3 per 100,000 vs. 27.0 in year in the year 2011 per 100,000. For women, the age-adjusted rate in 1988 was 6.07 per 100,000 vs. 11.4 in year 2011 per 100.000). CONCLUSION: Aortic valve surgery utilization has stabilized in recent years in both genders in the United States. However, this rate has been persistently more than double in men. The cause of this higher utilization in males needs further investigation.

Association between Factor-V Leiden and occurrence of acute myocardial infarction using a large NIS database.

Factor V Leiden is an inheritable pro-thrombotic genetic condition caused by a point mutation at the 506th codon, resulting in activated protein C resistance. APC resistance has been shown to contribute to the development of venous thrombosis. However, the role of FVL in AMI has yet to be well defined in the current literature. To assess whether a mutation carrier is more apt to develop an AMI, we conducted a retrospective observational analysis of two populations aged 18-40 and 18 through end of life. We used ICD-10 codes to search the NIS, an electronic nationwide patient database, to establish our populations and obtain our data. The ICD-10 codes were specific for activated protein C resistance and acute myocardial infarction. Preliminary data indicated that FVL was related to AMI; however, this finding became insignificant in both populations when stratified for age. We concluded there was no association between Factor V Leiden and acute myocardial infarction across both examined populations. Future investigations into this field of research are warranted as there remains a need for more consensus among the scientific community. BACKGROUND: Medical literature regarding the correlation between Factor V Leiden (FVL) and acute myocardial infarctions (AMI) is controversial. We aim to investigate the association between FVL and AMI. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample database, we evaluated any association between Factor V Leiden and acute myocardial infarction in 2016 using ICD-10 codes. RESULTS: Univariate analysis (18-40) showed an increase of AMI in patients with FVL 0.6% vs. 0.4%. However, after adjustment for age and comorbid conditions in multivariate analysis, FVL was not significantly associated with acute myocardial infarction (OR 1.44 (95% CI 0.913-2.273, p-value 0.117)). Univariate analysis (all patients over 18 years old) found that 2.9% of patients with FVL experienced AMI vs. 4.4% without the mutation. Multivariate analysis of the entire population ultimately showed no correlation between FVL and AMI. CONCLUSION: In a population over 18, Factor V Leiden did not correlate with an increased risk of acute myocardial infarction in our studied population.

A comprehensive review of the ten main platelet receptors involved in platelet activity and cardiovascular disease.

Cardiovascular disease (CVD) is a major cause of death worldwide. Although there are many variables that contribute to the development of this disease, it is predominantly the activity of platelets that provides the mechanisms by which this disease prevails. While there are numerous platelet receptors expressed on the surface of platelets, it is largely the consensus that there are 10 main platelet receptors that contribute to a majority of platelet function. Understanding these key platelet receptors is vitally important for patients suffering from myocardial infarction, CVD, and many other diseases that arise due to overactivation or mutations of these receptors. The goal of this manuscript is to review the main platelet receptors that contribute most to platelet activity.

Left ventricular hypertrophy is independently associated with all-cause mortality.

BACKGROUND: Left Ventricular Hypertrophy (LVH) is associated with adverse outcomes. The goal of this study was to evaluate any association between LVH and all-cause mortality using a large echocardiographic database. METHODS: We retrospectively evaluated 2,352 echocardiograms between the ages 16-99 years that were performed from 1983 to 1998 for clinical reasons in Southern California. Mortality data were extracted from the national mortality database at the end of the year 2007. Using uni- and multi-variant analysis, we evaluated any association between total mortality and echocardiographic presence of LVH defined as any wall thickness >11 mm. RESULTS: LVH was significantly associated with all-cause mortality [207/583 (35.5%) of patients died with LVH vs. 416/1769 (23.5%) of patients with normal wall thickness, P<0.001, HR 1.79, CI: 1.46-2.19]. Using multivariate analysis adjusting for age, gender, abnormal left ventricular systolic function, and significant valvular abnormalities, LVH remained independently associated with all-cause mortality (OR 1.39, CI 1.10-1.74, P=0.005). CONCLUSION: Using a large echocardiographic database, we found that LVH is independently associated with all-cause mortality. Our finding confirms the negative effect of LVH on the long-term outcome.

Splenectomy in patients with immune (idiopathic) thrombocytopenic purpura (ITP) appears to be protective against developing aortic valve disease.

BACKGROUND: Immune thrombocytopenia (ITP) has been shown to be independently associated with aortic valve disease (AVD). However, whether ITP patients who have undergone splenectomy are also at increased risk for AVD has not been researched. The goal of this study was to evaluate any association between AVD and splenectomy in patients with ITP. METHOD: We used the Nationwide Inpatient Sample from 2005 to 2014 as 10 consecutive years randomly selected. Using ICD-9 codes for AVD, ITP, and splenectomy, a total of 108,434 patients were identified with ITP, 4,282 of which had undergone splenectomy. We performed uni- and multivariate analysis adjusting for baseline characteristics. RESULTS: Univariate analysis revealed a significantly lower rate of AVD in ITP patients with splenectomy compared to no splenectomy in 2007, 2009, and 2010 with a trend of this association during the other years. For example, in 2007, 0.6% of ITP patients with history of splenectomy had AVD versus 2.0% of ITP patients without splenectomy (OR, 0.29; 95% CI, 0.09-0.91; P = 0.02). Similarly, in 2010, 0.2% of ITP patients with history of splenectomy had AVD versus 1.9% of ITP patients without splenectomy (OR, 0.13; 95% CI, 0.02-0.92; P = 0.02). After adjusting for age, gender, race, diabetes, hypertension, hyperlipidemia, and tobacco use, we confirmed that ITP patients with splenectomy have no association with prevalence of aortic valve disease (2005: OR, 0.48; 95% CI, 0.18-1.30; P = 0.15; 2014: OR, 0.88; 95% CI, 0.36-2.16; P = 0.77). CONCLUSION: Based on a large inpatient database, our previous finding of ITP patients' association with AVD is only present in patients without splenectomy, and splenectomy appears to exert a protective effect on developing aortic valve disease in ITP patients, warranting further investigation.

The effects of estrogen and hormone replacement therapy on platelet activity: a review.

Many studies have shown that an increase in cardiovascular disease in women is related to hormonal changes occurring particularly after menopause with increasing age. While the results of large clinical trials reporting no benefit of hormone replacement therapy (HRT) in cardiovascular disease have been known for some time, there is an increasing body of knowledge regarding the various mechanisms by which estrogen modulates platelet function that could in part explain the higher cardiovascular risk occurring in postmenopausal women and potential benefits of HRT on cardiovascular health. Our review summarizes our current knowledge regarding the effect of endogenous and exogenous estrogen on platelet activity, which can help researchers design future studies. We collected information from 21 peer-reviewed articles published from 1993 to 2021. Studies have indicated that postmenopausal women have higher platelet activity than premenopausal women, which can increase the risk of thrombo-embolic events and cardiovascular disease. Although some studies have reported pro-thrombotic effects of estrogen replacement therapy such as increased platelet activation and adhesion, other studies demonstrated decreased platelet aggregation by inhibiting GP IIb/IIIa receptor expression. This is mediated by estrogen receptors on the platelet membrane in a non-genomic manner and suggests an opportunity for the usage of estrogen replacement therapy with subtle changes in the formulation and route, particularly if started early after menopause. The effect of estrogen on platelet activity is promising as an important factor in reducing the risk of cardiovascular events, warranting further investigation.

All Aortic Valve Diseases Taken Together Are Not Associated With Obesity.

BACKGROUND: Obesity is a risk factor for cardiovascular disease. The goal of this study was to evaluate any association between aortic valve disease and obesity using a very large database. METHODS: The Nationwide Inpatient Sample database was utilized for statistical analysis using ICD-9 codes for aortic valve disease and obesity in the United States from 2003 to 2007. A 25% random sample of nonobese patients was used for comparison of aortic valve disease prevalence during the same 5-year period. RESULTS: A total of 1,971,812 patients with obesity were identified from 2003 to 2007. Comparing this population with a random sample of nonobese patients during the same years, there was no significant difference between obese and nonobese patients in regards to the prevalence of aortic valve disease (1.1-1.2% in 2003 and 2004, 1.2% in 2005-2007, P = NS). After adjusting for age, gender, and race, obesity was associated with lower prevalence of aortic valve disease in 2003-2007 (odds ratio 0.81-0.86, P < 0.01). CONCLUSIONS: Using a very large database, we found a decrease in the prevalence of aortic valve disease in the obese population. This suggests that obesity alone does not pathologically affect the aortic valve.

A Comprehensive Review of PCSK9 Inhibitors.

Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. A major risk factor for this condition is increased serum low-density lipoprotein cholesterol (LDL-C) levels for which statins have been successful in reducing serum LDL-C to healthy concentrations. However, patients who are statin intolerant or those who do not achieve their treatment goals while on high-intensity statin therapy, such as those with familial hypercholesterolemia, remain at risk. With the discovery of PCSK9 inhibitors, the ability to provide more aggressive treatment for patients with homozygous and heterozygous familial hypercholesterolemia has increased. Ezetimibe reduces LDL-C by 15%-20% when combined with statin.2,3 Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been found to achieve profound reductions in LDL-C (54%-74%) when added to statins. They have shown dramatic effects at lowering major adverse cardiovascular events (MACE) in high-risk patients4 with LDL-C levels ≥70 mg/dL and can be used in populations that are statin intolerant or not at goal levels with maximally tolerated statin therapy. PCSK9 inhibitors also produce minimal side effects. Myopathy, a common side effect for patients on statins, has been rare in patients on PCSK9 inhibitors. Randomized trials have shown that reduction in LDL-C has translated to clinical benefits even in patients who have not achieved their LDL-C target.

Novel antiplatelet agent ticagrelor in the management of acute coronary syndrome.

Current clinical guidelines recommend dual antiplatelet agents namely aspirin and clopidogrel for the treatment of patients suffering from acute coronary syndrome (ACS). But the efficacy of clopidogrel is variable as it is a pro-drug, which has to be metabolized to become an active drug thus exhibiting variable platelet inhibition, increases risk of bleeding, stent thrombosis, and ischemia. To overcome this limitation, prasugrel was developed with increased antiplatelet activity thereby reducing the risk of myocardial ischemia and stent thrombosis. This action of prasugrel was associated with an increased risk of major bleeding. Finally, a novel reversible and direct-acting oral adenosine diphosphate (ADP) receptor antagonist, ticagrelor was developed that showed consistent and increased P2Y12 inhibition with similar incidence of bleeding but greater reduction in cardiac events compared to clopidogrel. The focus of this article is to review ticagrelor as a new class of P2Y12 inhibitor.